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History of Changes for Study: NCT04270760
Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction - DOSE Finding Study
Latest version (submitted August 24, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 13, 2020 None (earliest Version on record)
2 July 2, 2020 Study Status
3 August 11, 2020 Recruitment Status, Study Status and Contacts/Locations
4 August 19, 2020 Contacts/Locations and Study Status
5 September 16, 2020 Study Status and Contacts/Locations
6 September 23, 2020 Contacts/Locations and Study Status
7 September 30, 2020 Contacts/Locations and Study Status
8 October 14, 2020 Study Status and Contacts/Locations
9 October 28, 2020 Contacts/Locations and Study Status
10 December 23, 2020 Study Status and Contacts/Locations
11 January 29, 2021 Arms and Interventions, Study Status, Study Identification, Contacts/Locations, Eligibility, Outcome Measures, Conditions and Study Description
12 February 3, 2021 Study Status and Contacts/Locations
13 February 17, 2021 Contacts/Locations and Study Status
14 May 7, 2021 Recruitment Status, Study Status, Contacts/Locations and Study Design
15 June 14, 2021 Study Status
16 September 22, 2021 Study Status and Contacts/Locations
17 November 19, 2021 Study Status
18 January 11, 2022 Study Status
19 July 15, 2022 Study Status and References
20 October 20, 2022 Study Status
21 November 16, 2022 Recruitment Status and Study Status
22 August 1, 2023 Outcome Measures, Study Status, More Information, Document Section, Adverse Events, Baseline Characteristics, Participant Flow and References
23 August 24, 2023 Study Status and Study Design
Comparison Format:
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Changes (Merged) for Study: NCT04270760
November 16, 2022 (v21) -- August 1, 2023 (v22)

Changes in: Study Status, Outcome Measures, References, Document Section, Participant Flow, Baseline Characteristics, Adverse Events and More Information
Open or close this module Study Identification
Unique Protocol ID: 20180109
Brief Title: Olpasiran Trials of Cardiovascular Events And LipoproteiN(a) Reduction - DOSE Finding Study
Official Title: A Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, and Tolerability of Olpasiran (AMG 890) in Subjects With Elevated Lipoprotein(a)
Secondary IDs: 2019-003688-23 [EudraCT Number]
Open or close this module Study Status
Record Verification: November 2022 July 2023
Overall Status: Completed
Study Start: July 28, 2020
Primary Completion: December 27, 2021 [Actual]
Study Completion: November 8, 2022 [Actual]
First Submitted: February 13, 2020
First Submitted that
Met QC Criteria:		 February 13, 2020
First Posted: February 17, 2020 [Actual]
Results First Submitted: August 1, 2023
Results First Submitted that
Met QC Criteria:		 August 1, 2023
Results First Posted: August 23, 2023 [Actual]
Certification/Extension
First Submitted:		 October 20, 2022
Certification/Extension
First Submitted that
Met QC Criteria:		 October 20, 2022
Certification/Extension
First Posted:		 October 24, 2022 [Actual]
Last Update Submitted that
Met QC Criteria:		 November 16, 2022 August 1, 2023
Last Update Posted: November 21, 2022 [Actual] August 23, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Amgen
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: Evaluate the effect of olpasiran administered subcutaneously (SC) compared with placebo, on percent change from baseline in lipoprotein(a) (Lp[a]).
Detailed Description:
Open or close this module Conditions
Conditions: Cardiovascular Disease
Keywords: Olpasiran
AMG 890
siRNA
lipoprotein (a) Lp(a)
Cardiovascular
Cardiovascular disease
Atherosclerotic cardiovascular disease
Cholesterol
Apolipoprotein (B)
Hyperlipidemia
Dyslipidemia
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 5
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 290 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Arm 1 Olpasiran Dose 1 Drug: Olpasiran
Dose 1 Dose 2 Dose 3 Dose 4
Other Names:
  • AMG 890
Active Comparator: Arm 2 Olpasiran Dose 2 Drug: Olpasiran
Dose 1 Dose 2 Dose 3 Dose 4
Other Names:
  • AMG 890
Active Comparator: Arm 3 Olpasiran Dose 3 Drug: Olpasiran
Dose 1 Dose 2 Dose 3 Dose 4
Other Names:
  • AMG 890
Active Comparator: Arm 4 Olpasiran Dose 4 Drug: Olpasiran
Dose 1 Dose 2 Dose 3 Dose 4
Other Names:
  • AMG 890
Placebo Comparator: Arm 5 Placebo Dose 5 Drug: Placebo
Dose 5
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Percent change in Lp(a) Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36
[ Time Frame: Baseline and week Week 36 ]

Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Secondary Outcome Measures:
1. Percentage change from baseline in Lp(a) Percentage Change From Baseline in Lp(a) at Week 48
[ Time Frame: Baseline and week Week 48 ]

Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
2. Percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48
[ Time Frame: Baseline and Weeks 36 and 48 Baseline; Week 36 and Week 48 ]

Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
3. Percentage change in Apolipoprotein(B) (ApoB) Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48
[ Time Frame: Baseline and weeks 36 and 48 Baseline; Week 36 and Week 48 ]

Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
4. Maximum observed concentration (Cmax) of Olpasiran Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48
[ Time Frame: 48 weeks Pre-dose and 1, 3, 6-12, and 24-72 hours post-dose on Day 1 and Week 24; Week 48 ]

Pharmacokinetic blood draws were collected at one timepoint during the 6-12 and 24-72 hour flexible time windows and at Week 48.

Lower limit of quantification (LLOQ) = 0.400 ng/mL. Values below the LLOQ were set to zero.

5 . Area under the concentration-time curve (AUC) of Olpasiran
[ Time Frame: 48 weeks ]
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 80 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Age 18 to 80 years
  • Lipoprotein (a) > 150 nmol/L
  • Evidence of atherosclerotic cardiovascular disease

Exclusion Criteria:

  • Severe renal dysfunction
  • History or clinical evidence of hepatic dysfunction
  • Malignancy within the last 5 years
  • Currently receiving, or less than 3 months at Day 1 since receiving > 200 mg/day Niacin
Open or close this module Contacts/Locations
Study Officials: MD
Study Director
Amgen
Locations: United States, California
Westside Medical Associates of Los Angeles
Beverly Hills, California, United States, 90211
United States, Florida
Excel Medical Clinical Trials
Boca Raton, Florida, United States, 33434
United States, Georgia
Piedmont Healthcare
Atlanta, Georgia, United States, 30309
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, New York
New York University
New York, New York, United States, 10016
Mount Sinai Hospital
New York, New York, United States, 10029
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Crossroads Clinical Research Inc
Mooresville, North Carolina, United States, 28117
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Protenium Clinical Research
Hurst, Texas, United States, 76054
Australia
Dr Heart Pty Ltd
Woolloongabba, Australia, 4102
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Core Research Group Pty Ltd
Milton, Queensland, Australia, 4064
Australia, Victoria
Monash Medical Centre
Clayton, Victoria, Australia, 3168
Australia, Western Australia
Linear Clinical Research Limited
Nedlands, Western Australia, Australia, 6009
Canada
Clinique des Maladies Lipidiques de Quebec Incorporated
Quebec, Canada, G1V 4W2
Canada, Ontario
LMC Clinical Research Incorporated
Brampton, Ontario, Canada, L6S 0C6
LMC Clinical Research Incorporated Thornhill
Concord, Ontario, Canada, L4K 4M2
Canada, Quebec
Ecogene-21
Chicoutimi, Quebec, Canada, G7H 7K9
Research Institute of McGill University Health Center - Glen Site
Montreal, Quebec, Canada, H4A 3J1
Denmark
Aarhus Universitetshospital
Aarhus N, Denmark, 8200
Herlev Gentofte Hospital
Herlev, Denmark, 2730
Regionshospitalet Viborg
Viborg, Denmark, 8800
Iceland
Thjonustumidstod Rannsoknaverkefna
Kopavogur, Iceland, 201
Japan, Chiba
Asahi General Hospital
Asahi-shi, Chiba, Japan, 289-2511
The Jikei University Kashiwa Hospital
Kashiwa-shi, Chiba, Japan, 277-8567
Japan, Hokkaido
Asahikawa City Hospital
Asahikawa-shi, Hokkaido, Japan, 070-8610
Japan, Ishikawa
Kanazawa Medical University Hospital
Kahoku-gun, Ishikawa, Japan, 920-0293
Japan, Saitama
Saitama Medical University Hospital
Iruma-gun, Saitama, Japan, 350-0495
Netherlands
Academisch Medisch Centrum
Amsterdam, Netherlands, 1105 AZ
Rijnstate Ziekenhuis
Arnhem, Netherlands, 6815 AD
Haga Ziekenhuis
The Hague, Netherlands, 2545 AA
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584 CX
VieCuri Medisch Centrum
Venlo, Netherlands, 5912 BL
Open or close this module IPDSharing
Plan to Share IPD: Yes
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame:
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria:
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: https://www.amgen.com/datasharing
Open or close this module References
Citations: O'Donoghue ML, G Lopez JA, Knusel B, Gencer B, Wang H, Wu Y, Kassahun H, Sabatine MS. Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE). Am Heart J. 2022 Sep;251:61-69. doi: 10.1016/j.ahj.2022.05.004. Epub 2022 May 16. PubMed 35588897
O'Donoghue ML, Rosenson RS, Gencer B, Lopez JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Ran X, Murphy SA, Wang H, Wu Y, Kassahun H, Sabatine MS; OCEAN(a)-DOSE Trial Investigators. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. N Engl J Med. 2022 Nov 17;387(20):1855-1864. doi: 10.1056/NEJMoa2211023. Epub 2022 Nov 6. PubMed 36342163
Links: Description: AmgenTrials clinical trials website
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: May 2, 2022
Uploaded: 08/01/2023 17:40
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: May 10, 2022
Uploaded: 08/01/2023 17:40
File Name: SAP_001.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details This study was conducted at 34 centers in Australia, Denmark, Iceland, the Netherlands, Canada, the United States, and Japan between 28 July 2020 and 08 November 2022.
Pre-assignment Details The Treatment Period was 48 weeks with investigational product (IP) administered subcutaneously (SC) every 12 weeks (Q12W) or 24 weeks (Q24W). After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants remained on standard of care per their local guidelines during the Treatment Period and Extended Safety Follow-up Period.
 
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W Group 5: Placebo Q12W
Arm/Group Description Participants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.
Period Title: Overall Study
Started 58 58 56 55 54
Entered Extended Safety Follow-up Period 57 57 54 55 53
Completed 57 55 52 55 53
Not Completed 1 3 4 0 1
Reason Not Completed
Withdrawal by Subject 0 1 3 0 0
Lost to Follow-up 1 2 1 0 0
Death 0 0 0 0 1
Open or close this module Baseline Characteristics
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W Group 5: Placebo Q12W Total
Arm/Group DescriptionParticipants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 58 58 56 55 54 281
Baseline Analysis Population Description
Age, Continuous
Mean ( Standard Deviation)
Unit of measure: Years
Number Analyzed 58 Participants 58 Participants 56 Participants 55 Participants 54 Participants 281 Participants
63.4 (9.5) 61.3 (9.2) 59.7 (10.1) 61.8 (9.4) 63.4 (8.9) 61.9 (9.5)
Age, Customized
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed 58 Participants 58 Participants 56 Participants 55 Participants 54 Participants 281 Participants
18 - 64 years
31
53.45%
35
60.34%
37
66.07%
31
56.36%
29
53.7%
163
58.01%
65 - 74 years
19
32.76%
17
29.31%
18
32.14%
19
34.55%
17
31.48%
90
32.03%
75 - 84 years
8
13.79%
6
10.34%
1
1.79%
5
9.09%
8
14.81%
28
9.96%
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed 58 Participants 58 Participants 56 Participants 55 Participants 54 Participants 281 Participants
Female
12
20.69%
23
39.66%
15
26.79%
22
40%
18
33.33%
90
32.03%
Male
46
79.31%
35
60.34%
41
73.21%
33
60%
36
66.67%
191
67.97%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed 58 Participants 58 Participants 56 Participants 55 Participants 54 Participants 281 Participants
Hispanic or Latino
2
3.45%
0
0%
0
0%
2
3.64%
2
3.7%
6
2.14%
Not Hispanic or Latino
56
96.55%
58
100%
56
100%
53
96.36%
52
96.3%
275
97.86%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Race/Ethnicity, Customized
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed 58 Participants 58 Participants 56 Participants 55 Participants 54 Participants 281 Participants
Asian
6
10.34%
5
8.62%
5
8.93%
5
9.09%
3
5.56%
24
8.54%
Black or African American
0
0%
1
1.72%
2
3.57%
1
1.82%
2
3.7%
6
2.14%
White
52
89.66%
52
89.66%
47
83.93%
49
89.09%
48
88.89%
248
88.26%
Other
0
0%
0
0%
2
3.57%
0
0%
1
1.85%
3
1.07%
Open or close this module Outcome Measures
1. Primary Outcome:
Title Percentage Change From Baseline in Lipoprotein(a) (Lp[a]) at Week 36
Description Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Time Frame Baseline and Week 36
Outcome Measure Data
Analysis Population Description
Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.
 
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W Group 5: Placebo Q12W
Arm/Group DescriptionParticipants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.
Overall Number of Participants Analyzed 57 57 53 53 51
Least Squares Mean (Standard Error)
Unit of Measure: Percentage Change in Lp(a)
 -66.91 (1.78) -93.78 (1.78) -97.53 (1.82) -96.89 (1.85) 3.60 (1.89)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group Selection Group 1: Olpasiran 10 mg Q12W, Group 5: Placebo Q12W
CommentsGroup 1 versus (vs) Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments Adjusted p-value is reported based on the Hochberg procedure to control the type I error for multiple comparisons. Each individual adjusted p-value is compared to 0.05 to determine statistical significance.
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -70.51
Confidence Interval (2-sided) 95%
-75.12 to -65.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.35
Estimation Comments Treatment difference = percentage change in Group 1 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group Selection Group 2: Olpasiran 75 mg Q12W, Group 5: Placebo Q12W
CommentsGroup 2 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments Adjusted p-value is reported based on the Hochberg procedure to control the type I error for multiple comparisons. Each individual adjusted p-value is compared to 0.05 to determine statistical significance.
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -97.38
Confidence Interval (2-sided) 95%
-101.98 to -92.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.35
Estimation Comments Treatment difference = percentage change in Group 2 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group Selection Group 3: Olpasiran 225 mg Q12W, Group 5: Placebo Q12W
CommentsGroup 3 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments Adjusted p-value is reported based on the Hochberg procedure to control the type I error for multiple comparisons. Each individual adjusted p-value is compared to 0.05 to determine statistical significance.
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -101.13
Confidence Interval (2-sided) 95%
-105.79 to -96.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.38
Estimation Comments Treatment difference = percentage change in Group 3 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group Selection Group 4: Olpasiran 225 mg Q24W, Group 5: Placebo Q12W
CommentsGroup 4 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value < 0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -100.49
Confidence Interval (2-sided) 95%
-105.16 to -95.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.38
Estimation Comments Treatment difference = percentage change in Group 4 - percentage change in Group 5 from Baseline at Week 36.
2. Secondary Outcome:
Title Percentage Change From Baseline in Lp(a) at Week 48
Description Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Time Frame Baseline and Week 48
Outcome Measure Data
Analysis Population Description
Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.
 
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W Group 5: Placebo Q12W
Arm/Group DescriptionParticipants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.
Overall Number of Participants Analyzed 57 57 54 53 51
Least Squares Mean (Standard Error)
Unit of Measure: Percentage Change in Lp(a)
 -64.89 (2.17) -92.54 (2.17) -97.29 (2.22) -82.36 (2.25) 3.59 (2.30)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group Selection Group 1: Olpasiran 10 mg Q12W, Group 5: Placebo Q12W
CommentsGroup 1 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -68.47
Confidence Interval (2-sided) 95%
-74.27 to -62.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.96
Estimation Comments Treatment difference = percentage change in Group 1 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group Selection Group 2: Olpasiran 75 mg Q12W, Group 5: Placebo Q12W
CommentsGroup 2 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -96.12
Confidence Interval (2-sided) 95%
-101.92 to -90.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.96
Estimation Comments Treatment difference = percentage change in Group 2 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group Selection Group 3: Olpasiran 225 mg Q12W, Group 5: Placebo Q12W
CommentsGroup 3 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -100.88
Confidence Interval (2-sided) 95%
-106.74 to -95.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.99
Estimation Comments Treatment difference = percentage change in Group 3 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group Selection Group 4: Olpasiran 225 mg Q24W, Group 5: Placebo Q12W
CommentsGroup 4 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value < 0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -85.94
Confidence Interval (2-sided) 95%
-91.83 to -80.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.00
Estimation Comments Treatment difference = percentage change in Group 4 - percentage change in Group 5 from Baseline at Week 48.
3. Secondary Outcome:
Title Percentage Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 36 and Week 48
Description Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Time Frame Baseline; Week 36 and Week 48
Outcome Measure Data
Analysis Population Description
Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.
   
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W Group 5: Placebo Q12W
Arm/Group DescriptionParticipants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.
Overall Number of Participants Analyzed 57 57 54 53 51
Least Squares Mean (Standard Error)
Unit of Measure: Percentage Change in LDL-C
 
Week 36
Number Analyzed Participants Participants Participants Participants Participants
-17.425 (4.258) -16.284 (4.259) -16.733 (4.389) -18.462 (4.428) 6.234 (4.520)
Week 48
Number Analyzed Participants Participants Participants Participants Participants
-14.743 (4.419) -11.481 (4.418) -17.308 (4.532) -16.908 (4.608) 10.113 (4.688)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group Selection Group 1: Olpasiran 10 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 36: Group 1 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -23.659
Confidence Interval (2-sided) 95%
-35.176 to -12.143
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.874
Estimation Comments Treatment difference = percentage change in Group 1 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group Selection Group 2: Olpasiran 75 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 36: Group 2 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -22.518
Confidence Interval (2-sided) 95%
-34.036 to -11.000
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.875
Estimation Comments Treatment difference = percentage change in Group 2 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group Selection Group 3: Olpasiran 225 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 36: Group 3 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -22.967
Confidence Interval (2-sided) 95%
-34.656 to -11.278
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.962
Estimation Comments Treatment difference = percentage change in Group 3 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group Selection Group 4: Olpasiran 225 mg Q24W, Group 5: Placebo Q12W
CommentsWeek 36: Group 4 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value < 0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -24.696
Confidence Interval (2-sided) 95%
-36.399 to -12.993
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.969
Estimation Comments Treatment difference = percentage change in Group 4 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 5
Statistical Analysis OverviewComparison Group Selection Group 1: Olpasiran 10 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 48: Group 1 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -24.856
Confidence Interval (2-sided) 95%
-36.853 to -12.859
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.119
Estimation Comments Treatment difference = percentage change in Group 1 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 6
Statistical Analysis OverviewComparison Group Selection Group 2: Olpasiran 75 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 48: Group 2 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -21.594
Confidence Interval (2-sided) 95%
-33.590 to -9.598
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.118
Estimation Comments Treatment difference = percentage change in Group 2 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 7
Statistical Analysis OverviewComparison Group Selection Group 3: Olpasiran 225 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 48: Group 3 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -27.421
Confidence Interval (2-sided) 95%
-39.565 to -15.277
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.194
Estimation Comments Treatment difference = percentage change in Group 3 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 8
Statistical Analysis OverviewComparison Group Selection Group 4: Olpasiran 225 mg Q24W, Group 5: Placebo Q12W
CommentsWeek 48: Group 4 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -27.021
Confidence Interval (2-sided) 95%
-39.240 to -14.801
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.232
Estimation Comments Treatment difference = percentage change in Group 4 - percentage change in Group 5 from Baseline at Week 48.
4. Secondary Outcome:
Title Percentage Change From Baseline in Apolipoprotein (B) (ApoB) at Week 36 and Week 48
Description Least squares mean is from the repeated measures linear effects model which includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit.
Time Frame Baseline; Week 36 and Week 48
Outcome Measure Data
Analysis Population Description
Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.
 
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W Group 5: Placebo Q12W
Arm/Group DescriptionParticipants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.
Overall Number of Participants Analyzed 57 57 54 53 52
Least Squares Mean (Standard Error)
Unit of Measure: Percentage Change in ApoB
Week 36
 -11.496 (2.886) -9.302 (2.885) -10.241 (2.960) -11.378 (3.012) 7.394 (3.066)
Week 48
 -7.748 (3.307) -4.768 (3.305) -7.218 (3.393) -9.548 (3.443) 12.292 (3.501)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group Selection Group 1: Olpasiran 10 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 36: Group 1 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -18.890
Confidence Interval (2-sided) 95%
-26.303 to -11.477
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.779
Estimation Comments Treatment difference = percentage change in Group 1 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 2
Statistical Analysis OverviewComparison Group Selection Group 2: Olpasiran 75 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 36: Group 2 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -16.696
Confidence Interval (2-sided) 95%
-24.107 to -9.284
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.778
Estimation Comments Treatment difference = percentage change in Group 2 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 3
Statistical Analysis OverviewComparison Group Selection Group 3: Olpasiran 225 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 36: Group 3 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -17.635
Confidence Interval (2-sided) 95%
-25.139 to -10.131
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.825
Estimation Comments Treatment difference = percentage change in Group 3 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 4
Statistical Analysis OverviewComparison Group Selection Group 4: Olpasiran 225 mg Q24W, Group 5: Placebo Q12W
CommentsWeek 36: Group 4 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value < 0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -18.772
Confidence Interval (2-sided) 95%
-26.303 to -11.241
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.839
Estimation Comments Treatment difference = percentage change in Group 4 - percentage change in Group 5 from Baseline at Week 36.
Statistical Analysis 5
Statistical Analysis OverviewComparison Group Selection Group 1: Olpasiran 10 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 48: Group 1 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -20.040
Confidence Interval (2-sided) 95%
-28.757 to -11.323
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.443
Estimation Comments Treatment difference = percentage change in Group 1 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 6
Statistical Analysis OverviewComparison Group Selection Group 2: Olpasiran 75 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 48: Group 2 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -17.060
Confidence Interval (2-sided) 95%
-25.774 to -8.345
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.442
Estimation Comments Treatment difference = percentage change in Group 2 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 7
Statistical Analysis OverviewComparison Group Selection Group 3: Olpasiran 225 mg Q12W, Group 5: Placebo Q12W
CommentsWeek 48: Group 3 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -19.509
Confidence Interval (2-sided) 95%
-28.336 to -10.682
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.500
Estimation Comments Treatment difference = percentage change in Group 3 - percentage change in Group 5 from Baseline at Week 48.
Statistical Analysis 8
Statistical Analysis OverviewComparison Group Selection Group 4: Olpasiran 225 mg Q24W, Group 5: Placebo Q12W
CommentsWeek 48: Group 4 vs Group 5
Type of Statistical Test Superiority
Comments[Not specified]
Statistical Test of HypothesisP-Value <0.001
Comments[Not specified]
Method Repeated measures linear effects model
Comments Includes treatment group, stratification factors, scheduled visit and the interaction of treatment group with scheduled visit as covariates.
Method of EstimationEstimation Parameter Treatment difference
Estimated Value -21.839
Confidence Interval (2-sided) 95%
-30.700 to -12.979
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.517
Estimation Comments Treatment difference = percentage change in Group 4 - percentage change in Group 5 from Baseline at Week 48.
5. Secondary Outcome:
Title Mean Serum Olpasiran Concentrations at Day 1, Week 24 and Week 48
Description

Pharmacokinetic blood draws were collected at one timepoint during the 6-12 and 24-72 hour flexible time windows and at Week 48.

Lower limit of quantification (LLOQ) = 0.400 ng/mL. Values below the LLOQ were set to zero.

Time Frame Pre-dose and 1, 3, 6-12, and 24-72 hours post-dose on Day 1 and Week 24; Week 48
Outcome Measure Data
Analysis Population Description
Participants in the FAS with data available at each time point. FAS: includes all randomized participants who received at least one dose of IP.
   
Arm/Group Title Group 1: Olpasiran 10 mg Q12W Group 2: Olpasiran 75 mg Q12W Group 3: Olpasiran 225 mg Q12W Group 4: Olpasiran 225 mg Q24W
Arm/Group DescriptionParticipants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. After Week 48 there was an Extended Safety Follow-up Period without further dosing with IP for a minimum of 24 weeks.
Overall Number of Participants Analyzed 55 56 49 52
Mean (Standard Deviation)
Unit of Measure: ng/mL
 
Day 1: Pre-dose
Number Analyzed Participants Participants Participants Participants
0.00 (0.00) 0.00 (0.00) 0.00 (0.00) 0.00 (0.00)
Day 1: 1 Hour Post-dose
Number Analyzed Participants Participants Participants Participants
12.3 (6.9) 67.1 (47.4) 220 (218) 275 (450)
Day 1: 3 Hours Post-dose
Number Analyzed Participants Participants Participants Participants
18 (9.85) 80.3 (43.2) 291 (273) 324 (383)
Day 1: 6-12 Hours Post-dose
Number Analyzed Participants Participants Participants Participants
18.6 (10.1) 61.7 (36) 420 (432) 329 (191)
Day 1: 24-72 Hours Post-dose
Number Analyzed Participants Participants Participants Participants
0.995 (0.946) 20.4 (13.2) 63.2 (59.7) 103 (47.3)
Week 24: Pre-dose
Number Analyzed Participants Participants Participants Participants
0.00 (0.00) 0.0315 (0.134) 0.498 (1.88) 0.0645 (0.22)
Week 24: 1 Hour Post-dose
Number Analyzed Participants Participants Participants Participants
12.4 (7.23) 73.6 (43.6) 204 (144) 253 (247)
Week 24: 3 Hours Post-dose
Number Analyzed Participants Participants Participants Participants
16.3 (9.2) 96.3 (63.5) 278 (193) 332 (255)
Week 24: 6-12 Hours Post-dose
Number Analyzed Participants Participants Participants Participants
17.2 (10.2) 76.3 (54.7) 271 (229) 315 (191)
Week 24: 24-72 Hours Post-dose
Number Analyzed Participants Participants Participants Participants
1.27 (1.82) 17.3 (18.9) 99 (59.1) 96.3 (50.3)
Week 48
Number Analyzed Participants Participants Participants Participants
0.00 (0.00) 0.0599 (0.168) 0.533 (0.592) 0.127 (0.693)
Open or close this module Adverse Events
 
Time Frame Treatment Period: Median duration was 11.07 months. Extended Safety Follow-up Period: Median duration was 8.56 months.
Adverse Event Reporting Description FAS: includes all randomized participants who received at least one dose of IP. For safety analysis FAS was used based on actual treatment received.
 
Arm/Group Title Group 1; Treatment Period: Olpasiran 10 mg Q12W Group 2; Treatment Period: Olpasiran 75 mg Q12W Group 3; Treatment Period: Olpasiran 225 mg Q12W Group 4; Treatment Period: Olpasiran 225 mg Q24W Group 5; Treatment Period: Placebo Q12W Group 1; Extended Safety Follow-up Period: Olpasiran 10 mg Q12W Group 2; Extended Safety Follow-up Period: Olpasiran 75 mg Q12W Group 3; Extended Safety Follow-up Period: Olpasiran 225 mg Q12W Group 4; Extended Safety Follow-up Period: Olpasiran 225 mg Q24W Group 5; Extended Safety Follow-up: Placebo Q12W
Arm/Group Description Participants were administered SC olpasiran 10 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. Participants were administered SC olpasiran 75 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. Participants were administered SC olpasiran 225 mg Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. Participants were administered SC olpasiran 225 mg Q24W for 48 weeks with doses at Day 1 and Week 24. Participants were administered SC placebo Q12W for 48 weeks with doses at Day 1, Week 12, Week 24, and Week 36. After Week 48 there was an extended safety follow-up without further dosing with IP for a minimum of 24 weeks. After Week 48 there was an extended safety follow-up without further dosing with IP for a minimum of 24 weeks. After Week 48 there was an extended safety follow-up without further dosing with IP for a minimum of 24 weeks. After Week 48 there was an extended safety follow-up without further dosing with IP for a minimum of 24 weeks. After Week 48 there was an extended safety follow-up without further dosing with IP for a minimum of 24 weeks.
All-Cause Mortality
  Group 1; Treatment Period: Olpasiran 10 mg Q12W Group 2; Treatment Period: Olpasiran 75 mg Q12W Group 3; Treatment Period: Olpasiran 225 mg Q12W Group 4; Treatment Period: Olpasiran 225 mg Q24W Group 5; Treatment Period: Placebo Q12W Group 1; Extended Safety Follow-up Period: Olpasiran 10 mg Q12W Group 2; Extended Safety Follow-up Period: Olpasiran 75 mg Q12W Group 3; Extended Safety Follow-up Period: Olpasiran 225 mg Q12W Group 4; Extended Safety Follow-up Period: Olpasiran 225 mg Q24W Group 5; Extended Safety Follow-up: Placebo Q12W
 Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Serious Adverse Events
  Group 1; Treatment Period: Olpasiran 10 mg Q12W Group 2; Treatment Period: Olpasiran 75 mg Q12W Group 3; Treatment Period: Olpasiran 225 mg Q12W Group 4; Treatment Period: Olpasiran 225 mg Q24W Group 5; Treatment Period: Placebo Q12W Group 1; Extended Safety Follow-up Period: Olpasiran 10 mg Q12W Group 2; Extended Safety Follow-up Period: Olpasiran 75 mg Q12W Group 3; Extended Safety Follow-up Period: Olpasiran 225 mg Q12W Group 4; Extended Safety Follow-up Period: Olpasiran 225 mg Q24W Group 5; Extended Safety Follow-up: Placebo Q12W
 Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)
Total 3 / 58 ( 5.17%) 3 / 58 ( 5.17%) 6 / 56 ( 10.71%) 4 / 55 ( 7.27%) 8 / 54 ( 14.81%) 4 / 57 ( 7.02%) 2 / 57 ( 3.51%) 6 / 54 ( 11.11%) 5 / 55 ( 9.09%) 4 / 53 ( 7.55%)
Cardiac disorders
Angina pectoris † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 1 / 57 ( 1.75%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Angina unstable † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Atrial fibrillation † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 0 / 56 ( 0%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Atrial flutter † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Bradycardia † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Eye disorders
Cataract † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 1 / 57 ( 1.75%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Gastrointestinal disorders
Colitis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Diarrhoea † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Rectal haemorrhage † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Upper gastrointestinal haemorrhage † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 1 / 57 ( 1.75%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
General disorders
Injection site reaction † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Injection site urticaria † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Non-cardiac chest pain † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Hepatobiliary disorders
Cholangitis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Infections and infestations
Abdominal abscess † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
COVID-19 pneumonia † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Campylobacter infection † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Cellulitis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Diverticulitis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Diverticulitis intestinal perforated † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Influenza † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Pneumonia † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Urinary tract infection † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Vestibular neuronitis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Injury, poisoning and procedural complications
Fall † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Femur fracture † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Hip fracture † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Rib fracture † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Traumatic haematoma † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Metabolism and nutrition disorders
Obesity † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Fistula † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Osteoarthritis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 2 / 54 ( 3.7%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer stage IV † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Gastrointestinal cancer metastatic † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Gastrointestinal carcinoma † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Malignant melanoma stage I † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Metastases to pancreas † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Prostate cancer recurrent † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Nervous system disorders
Cerebrovascular accident † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Ischaemic stroke † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Partial seizures † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 1 / 57 ( 1.75%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Seizure † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Syncope † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Product Issues
Device inappropriate shock delivery † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Psychiatric disorders
Depression † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Renal and urinary disorders
Ureterolithiasis † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Urinoma † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Skin and subcutaneous tissue disorders
Urticaria † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Vascular disorders
Aortic stenosis † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Hypertension † A 0 / 58 ( 0%) 0 / 58 ( 0%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Iliac artery occlusion † A 0 / 58 ( 0%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
† Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 25.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  Group 1; Treatment Period: Olpasiran 10 mg Q12W Group 2; Treatment Period: Olpasiran 75 mg Q12W Group 3; Treatment Period: Olpasiran 225 mg Q12W Group 4; Treatment Period: Olpasiran 225 mg Q24W Group 5; Treatment Period: Placebo Q12W Group 1; Extended Safety Follow-up Period: Olpasiran 10 mg Q12W Group 2; Extended Safety Follow-up Period: Olpasiran 75 mg Q12W Group 3; Extended Safety Follow-up Period: Olpasiran 225 mg Q12W Group 4; Extended Safety Follow-up Period: Olpasiran 225 mg Q24W Group 5; Extended Safety Follow-up: Placebo Q12W
 Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)Affected / At Risk (%)
Total 35 / 58 ( 60.34%) 40 / 58 ( 68.97%) 37 / 56 ( 66.07%) 36 / 55 ( 65.45%) 29 / 54 ( 53.7%) 18 / 57 ( 31.58%) 25 / 57 ( 43.86%) 21 / 54 ( 38.89%) 17 / 55 ( 30.91%) 17 / 53 ( 32.08%)
Blood and lymphatic system disorders
Anaemia † A 3 / 58 ( 5.17%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 1 / 55 ( 1.82%) 0 / 54 ( 0%) 1 / 57 ( 1.75%) 2 / 57 ( 3.51%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Gastrointestinal disorders
Abdominal pain † A 0 / 58 ( 0%) 0 / 58 ( 0%) 3 / 56 ( 5.36%) 2 / 55 ( 3.64%) 2 / 54 ( 3.7%) 1 / 57 ( 1.75%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Constipation † A 3 / 58 ( 5.17%) 0 / 58 ( 0%) 1 / 56 ( 1.79%) 2 / 55 ( 3.64%) 2 / 54 ( 3.7%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Diarrhoea † A 2 / 58 ( 3.45%) 3 / 58 ( 5.17%) 3 / 56 ( 5.36%) 1 / 55 ( 1.82%) 4 / 54 ( 7.41%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Gastrooesophageal reflux disease † A 1 / 58 ( 1.72%) 1 / 58 ( 1.72%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 2 / 54 ( 3.7%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 3 / 53 ( 5.66%)
Nausea † A 2 / 58 ( 3.45%) 1 / 58 ( 1.72%) 2 / 56 ( 3.57%) 3 / 55 ( 5.45%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 2 / 55 ( 3.64%) 1 / 53 ( 1.89%)
General disorders
Fatigue † A 6 / 58 ( 10.34%) 8 / 58 ( 13.79%) 3 / 56 ( 5.36%) 2 / 55 ( 3.64%) 3 / 54 ( 5.56%) 2 / 57 ( 3.51%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Injection site bruising † A 0 / 58 ( 0%) 4 / 58 ( 6.9%) 5 / 56 ( 8.93%) 0 / 55 ( 0%) 4 / 54 ( 7.41%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Injection site erythema † A 0 / 58 ( 0%) 3 / 58 ( 5.17%) 3 / 56 ( 5.36%) 4 / 55 ( 7.27%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Injection site pain † A 2 / 58 ( 3.45%) 3 / 58 ( 5.17%) 1 / 56 ( 1.79%) 5 / 55 ( 9.09%) 2 / 54 ( 3.7%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Injection site pruritus † A 1 / 58 ( 1.72%) 0 / 58 ( 0%) 0 / 56 ( 0%) 3 / 55 ( 5.45%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Non-cardiac chest pain † A 2 / 58 ( 3.45%) 2 / 58 ( 3.45%) 1 / 56 ( 1.79%) 4 / 55 ( 7.27%) 1 / 54 ( 1.85%) 2 / 57 ( 3.51%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Oedema peripheral † A 2 / 58 ( 3.45%) 1 / 58 ( 1.72%) 1 / 56 ( 1.79%) 3 / 55 ( 5.45%) 0 / 54 ( 0%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 2 / 54 ( 3.7%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Immune system disorders
Immunisation reaction † A 8 / 58 ( 13.79%) 4 / 58 ( 6.9%) 2 / 56 ( 3.57%) 4 / 55 ( 7.27%) 5 / 54 ( 9.26%) 0 / 57 ( 0%) 0 / 57 ( 0%) 2 / 54 ( 3.7%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Infections and infestations
COVID-19 † A 1 / 58 ( 1.72%) 8 / 58 ( 13.79%) 7 / 56 ( 12.5%) 4 / 55 ( 7.27%) 6 / 54 ( 11.11%) 8 / 57 ( 14.04%) 11 / 57 ( 19.3%) 14 / 54 ( 25.93%) 10 / 55 ( 18.18%) 10 / 53 ( 18.87%)
Gastroenteritis † A 1 / 58 ( 1.72%) 4 / 58 ( 6.9%) 0 / 56 ( 0%) 2 / 55 ( 3.64%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
Nasopharyngitis † A 2 / 58 ( 3.45%) 2 / 58 ( 3.45%) 4 / 56 ( 7.14%) 1 / 55 ( 1.82%) 1 / 54 ( 1.85%) 3 / 57 ( 5.26%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 2 / 55 ( 3.64%) 0 / 53 ( 0%)
Sinusitis † A 0 / 58 ( 0%) 3 / 58 ( 5.17%) 0 / 56 ( 0%) 2 / 55 ( 3.64%) 0 / 54 ( 0%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Upper respiratory tract infection † A 4 / 58 ( 6.9%) 3 / 58 ( 5.17%) 2 / 56 ( 3.57%) 1 / 55 ( 1.82%) 2 / 54 ( 3.7%) 2 / 57 ( 3.51%) 2 / 57 ( 3.51%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 1 / 53 ( 1.89%)
Urinary tract infection † A 3 / 58 ( 5.17%) 4 / 58 ( 6.9%) 2 / 56 ( 3.57%) 1 / 55 ( 1.82%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 4 / 57 ( 7.02%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Injury, poisoning and procedural complications
Contusion † A 0 / 58 ( 0%) 1 / 58 ( 1.72%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 3 / 54 ( 5.56%) 1 / 57 ( 1.75%) 2 / 57 ( 3.51%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Fall † A 2 / 58 ( 3.45%) 3 / 58 ( 5.17%) 1 / 56 ( 1.79%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 2 / 55 ( 3.64%) 0 / 53 ( 0%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus † A 3 / 58 ( 5.17%) 3 / 58 ( 5.17%) 1 / 56 ( 1.79%) 2 / 55 ( 3.64%) 2 / 54 ( 3.7%) 1 / 57 ( 1.75%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Musculoskeletal and connective tissue disorders
Arthralgia † A 2 / 58 ( 3.45%) 3 / 58 ( 5.17%) 3 / 56 ( 5.36%) 2 / 55 ( 3.64%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 1 / 54 ( 1.85%) 1 / 55 ( 1.82%) 1 / 53 ( 1.89%)
Back pain † A 6 / 58 ( 10.34%) 5 / 58 ( 8.62%) 7 / 56 ( 12.5%) 1 / 55 ( 1.82%) 3 / 54 ( 5.56%) 3 / 57 ( 5.26%) 1 / 57 ( 1.75%) 1 / 54 ( 1.85%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Myalgia † A 3 / 58 ( 5.17%) 1 / 58 ( 1.72%) 4 / 56 ( 7.14%) 4 / 55 ( 7.27%) 4 / 54 ( 7.41%) 2 / 57 ( 3.51%) 0 / 57 ( 0%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Pain in extremity † A 2 / 58 ( 3.45%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 3 / 55 ( 5.45%) 1 / 54 ( 1.85%) 1 / 57 ( 1.75%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Nervous system disorders
Areflexia † A 0 / 58 ( 0%) 3 / 58 ( 5.17%) 0 / 56 ( 0%) 0 / 55 ( 0%) 0 / 54 ( 0%) 0 / 57 ( 0%) 0 / 57 ( 0%) 1 / 54 ( 1.85%) 0 / 55 ( 0%) 0 / 53 ( 0%)
Dizziness † A 0 / 58 ( 0%) 3 / 58 ( 5.17%) 2 / 56 ( 3.57%) 1 / 55 ( 1.82%) 2 / 54 ( 3.7%) 0 / 57 ( 0%) 0 / 57 ( 0%) 0 / 54 ( 0%) 1 / 55 ( 1.82%) 1 / 53 ( 1.89%)
Headache † A 6 / 58 ( 10.34%) 7 / 58 ( 12.07%) 6 / 56 ( 10.71%) 6 / 55 ( 10.91%) 4 / 54 ( 7.41%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 2 / 54 ( 3.7%) 1 / 55 ( 1.82%) 0 / 53 ( 0%)
Respiratory, thoracic and mediastinal disorders
Cough † A 3 / 58 ( 5.17%) 1 / 58 ( 1.72%) 0 / 56 ( 0%) 0 / 55 ( 0%) 1 / 54 ( 1.85%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 3 / 53 ( 5.66%)
Vascular disorders
Hypertension † A 4 / 58 ( 6.9%) 2 / 58 ( 3.45%) 3 / 56 ( 5.36%) 2 / 55 ( 3.64%) 2 / 54 ( 3.7%) 0 / 57 ( 0%) 1 / 57 ( 1.75%) 0 / 54 ( 0%) 0 / 55 ( 0%) 1 / 53 ( 1.89%)
† Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 25.1
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact:
Name/Official Title:
 Study Director
Organization:
 Amgen Inc.
Phone:
 866-572-6436
Email:
 medinfo@amgen.com
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