History of Changes for Study: NCT05079919

A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia

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Study Record Versions

Version	Submitted Date	Changes
1	October 4, 2021	None (earliest Version on record)
2	October 26, 2021	Contacts/Locations and Study Status
3	January 12, 2022	Recruitment Status, Study Status and Contacts/Locations
4	January 18, 2022	Contacts/Locations and Study Status
5	February 7, 2022	Study Status and Contacts/Locations
6	February 18, 2022	Contacts/Locations and Study Status
7	March 9, 2022	Arms and Interventions, Study Description, Study Status, Contacts/Locations, Eligibility, Outcome Measures, Study Design, Conditions and Study Identification
8	March 28, 2022	Contacts/Locations and Study Status
9	April 11, 2022	Study Status and Contacts/Locations
10	April 14, 2022	Contacts/Locations and Study Status
11	June 20, 2022	Study Status and Contacts/Locations
12	June 29, 2022	Contacts/Locations and Study Status
13	July 25, 2022	Study Status and Contacts/Locations
14	August 1, 2022	Study Status and Contacts/Locations
15	August 2, 2022	Contacts/Locations and Study Status
16	August 4, 2022	Study Status
17	August 6, 2022	Contacts/Locations and Study Status
18	August 17, 2022	Contacts/Locations and Study Status
19	August 19, 2022	Contacts/Locations and Study Status
20	September 7, 2022	Study Design, Study Status and Contacts/Locations
21	September 12, 2022	Contacts/Locations and Study Status
22	September 20, 2022	Contacts/Locations and Study Status
23	September 23, 2022	Contacts/Locations and Study Status
24	September 28, 2022	Contacts/Locations and Study Status
25	October 5, 2022	Study Status and Contacts/Locations
26	October 13, 2022	Contacts/Locations and Study Status
27	October 14, 2022	Contacts/Locations and Study Status
28	October 23, 2022	Contacts/Locations and Study Status
29	November 3, 2022	Study Status and Contacts/Locations
30	November 23, 2022	Contacts/Locations and Study Status
31	November 28, 2022	Contacts/Locations and Study Status
32	November 30, 2022	Contacts/Locations and Study Status
33	December 7, 2022	Study Status and Contacts/Locations
34	December 19, 2022	Contacts/Locations and Study Status
35	January 4, 2023	Study Status and Contacts/Locations
36	January 12, 2023	Contacts/Locations and Study Status
37	January 23, 2023	Contacts/Locations and Study Status
38	February 8, 2023	Study Status and Contacts/Locations
39	February 15, 2023	Contacts/Locations and Study Status
40	February 21, 2023	Contacts/Locations and Study Status
41	February 27, 2023	Contacts/Locations and Study Status
42	March 24, 2023	Study Status and Contacts/Locations
43	March 27, 2023	Study Status
44	April 11, 2023	Study Status and Contacts/Locations
45	April 19, 2023	Contacts/Locations and Study Status
46	May 8, 2023	Study Status and Contacts/Locations
47	May 16, 2023	Contacts/Locations and Study Status
48	May 30, 2023	Contacts/Locations and Study Status
49	June 6, 2023	Study Status and Contacts/Locations
50	June 13, 2023	Contacts/Locations and Study Status
51	June 22, 2023	Contacts/Locations and Study Status
52	July 5, 2023	Study Status and Contacts/Locations
53	July 18, 2023	Contacts/Locations and Study Status
54	July 26, 2023	Contacts/Locations, Outcome Measures, Study Description and Study Status
55	August 2, 2023	Study Status and Contacts/Locations
56	August 21, 2023	Contacts/Locations and Study Status
57	August 25, 2023	Contacts/Locations and Study Status
58	September 7, 2023	Study Status and Contacts/Locations
59	September 15, 2023	Contacts/Locations and Study Status
60	September 22, 2023	Contacts/Locations and Study Status
61	October 4, 2023	Study Status and Contacts/Locations
62	October 18, 2023	Contacts/Locations and Study Status
63	November 14, 2023	Study Status and Contacts/Locations
64	November 22, 2023	Contacts/Locations and Study Status
65	November 29, 2023	Contacts/Locations and Study Status
66	December 14, 2023	Study Status and Contacts/Locations
67	December 21, 2023	Contacts/Locations and Study Status
68	January 26, 2024	Study Status and Contacts/Locations
69	May 9, 2024	Study Status
70	May 10, 2024	Recruitment Status, Study Status, Contacts/Locations and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	ISIS 678354-CS5
Brief Title:	A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia
Official Title:	A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of ISIS 678354 Administered Subcutaneously to Patients With Severe Hypertriglyceridemia
Secondary IDs:	2021-002192-19 [EudraCT Number]

Study Status


Record Verification:	November 2022
Overall Status:	Recruiting
Study Start:	October 25, 2021
Primary Completion:	October 2024 [Anticipated]
Study Completion:	February 2025 [Anticipated]

First Submitted:	October 4, 2021
First Submitted that Met QC Criteria:	October 4, 2021
First Posted:	October 15, 2021 [Actual]

Last Update Submitted that Met QC Criteria:	November 28, 2022
Last Update Posted:	November 29, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Ionis Pharmaceuticals, Inc.
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description

Brief Summary:

The purpose of the study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.

Detailed Description:

This is a multi-center, randomized, double-blind, placebo-controlled study in up to approximately 540 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 74 weeks, which includes an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.

Conditions


Conditions:	Severe Hypertriglyceridemia
Keywords:	ISIS 678354 Fasting Triglycerides Apolipoprotein C-III Very Low-Density Lipoprotein Cholesterol High-Density Lipoprotein-Cholesterol Non-High-Density Lipoprotein-Cholesterol Olezarsen

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Triple (Participant, Care Provider, Investigator)
Allocation:	Randomized
Enrollment:	540 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Olezarsen Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.	Drug: Olezarsen Olezarsen will be administered by SC injection. Other Names: AKCEA-APOCIII-LRx ISIS 678354
Placebo Comparator: Placebo Olezarsen-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49.	Drug: Placebo Olezarsen-matching placebo will be administered by SC injection.

Outcome Measures


Primary Outcome Measures:
1.	Percent Change from Baseline in Fasting TG at 6 Months (Average of Weeks 25 and 27) Compared to Placebo [ Time Frame: Baseline and Month 6 ]
Secondary Outcome Measures:
1.	Percent Change from Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) Compared to Placebo [ Time Frame: Baseline and Month 12 ]
2.	Proportion of Participants Who Achieve Fasting TG Less Than (<) 500 milligrams per deciliter (mg/dL) (5.7 millimoles per liter [mmol/L]) at 6 and 12 Months Compared to Placebo [ Time Frame: Month 6 and 12 ]
3.	Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 880 mg/dL [ Time Frame: Month 6 and 12 ]
4.	Proportion of Participants Who Achieve Fasting TG < 1000 mg/dL (11.29 mmol/L) at 6 and 12 Months Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 1000 mg/dL [ Time Frame: Month 6 and Month 12 ]
5.	Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
6.	Percent Change from Baseline in Fasting Very Low-Density Lipoprotein Cholesterol (VLDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
7.	Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
8.	Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at 6 and 12 Months Compared to Placebo [ Time Frame: Baseline, Month 6 and 12 ]
9.	Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo, in Participants with ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Enrollment [ Time Frame: Week 1 through Week 53 ]
10.	Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo [ Time Frame: Week 1 through Week 53 ]

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Key Inclusion Criteria: Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification Patients must be on lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study. Key Exclusion Criteria: Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal Total bilirubin > upper limit of normal unless due to Gilbert's syndrome Estimated GFR < 30 mL/min/1.73 m^2

Contacts/Locations


Central Contact Person:	Ionis Pharmaceuticals Telephone: (844) 980-5110 Email: ionisNCT05079919study@clinicaltrialmedia.com
Locations:	United States, California
	Velocity Clinical Research [Recruiting] Chula Vista, California, United States, 91911
	Diabetes/Lipid Management & Research Center [Recruiting] Huntington Beach, California, United States, 92648
	America Clinical Trials [Recruiting] Tarzana, California, United States, 91356
	United States, Florida
	Excel Medical Clinical Trials, LLC [Recruiting] Boca Raton, Florida, United States, 33434
	Finlay Medical Research [Recruiting] Miami, Florida, United States, 33126
	Ocala Cardiovascular Research [Recruiting] Ocala, Florida, United States, 34471
	Bayside Clinical Research [Recruiting] Trinity, Florida, United States, 34655
	United States, Georgia
	IACT Health [Recruiting] Columbus, Georgia, United States, 31904
	United States, Illinois
	Affinity Health [Recruiting] Oak Brook, Illinois, United States, 60523
	United States, Iowa
	West Broadway Clinic [Recruiting] Council Bluffs, Iowa, United States, 51501
	United States, Kansas
	Kansas University Medical Center [Recruiting] Kansas City, Kansas, United States, 66160
	United States, Maryland
	Continental Clinical Solutions [Recruiting] Towson, Maryland, United States, 21204
	United States, Michigan
	University of Michigan Hospital and Health Systems/ Dept. of Pharmacy-Research Pharmacy [Recruiting] Ann Arbor, Michigan, United States, 48109
	Aa Mrc, Llc [Recruiting] Flint, Michigan, United States, 48504
	United States, Missouri
	Washington University School of Medicine [Recruiting] Saint Louis, Missouri, United States, 63110
	United States, New York
	Northwell Health [Recruiting] Great Neck, New York, United States, 11021
	NYU Langone [Recruiting] New York, New York, United States, 10016
	United States, North Carolina
	Novant Health Cancer Institute Elizabeth Investigational Drug Services [Recruiting] Charlotte, North Carolina, United States, 28204
	Cone Medical Center [Recruiting] Greensboro, North Carolina, United States, 27401
	United States, Ohio
	Aventiv Research [Recruiting] Columbus, Ohio, United States, 43213
	Summit Research Group, LLC [Recruiting] Munroe Falls, Ohio, United States, 44262
	United States, Oklahoma
	Hightower Clinical Trial Services [Recruiting] Oklahoma City, Oklahoma, United States, 73102
	United States, Oregon
	Velocity Clinical Research [Recruiting] Medford, Oregon, United States, 97504
	United States, South Dakota
	Health Concepts [Recruiting] Rapid City, South Dakota, United States, 57702
	United States, Texas
	Velocity Clinical Research [Recruiting] Cedar Park, Texas, United States, 78613
	University of Texas Southwestern [Recruiting] Dallas, Texas, United States, 75390
	Baylor College of Medicine [Recruiting] Houston, Texas, United States, 77030
	United States, Utah
	Velocity Clinical [Recruiting] West Jordan, Utah, United States, 84088
	United States, Virginia
	Manassas Clinical Research Center [Recruiting] Manassas, Virginia, United States, 20110
	York Clinical Research LLC [Recruiting] Norfolk, Virginia, United States, 23510
	United States, West Virginia
	West Virginia University Heart and Vascular Institute [Recruiting] Morgantown, West Virginia, United States, 26506
	Australia, New South Wales
	Royal Prince Alfred Hospital [Recruiting] Camperdown, New South Wales, Australia, 2050
	Australia, Queensland
	Dr. Heart Pty Ltd at Cholesterol Care Australia [Recruiting] Woolloongabba, Queensland, Australia, 4102
	Australia, Victoria
	Monash Medical Centre [Recruiting] Clayton S., Victoria, Australia, 3168
	Bulgaria
	Medical Center Doctor Staykov EOOD [Recruiting] Burgas, Bulgaria, 8008
	Medical Center Diamedical 2013 OOD [Recruiting] Dimitrovgrad, Bulgaria, 6400
	Medical Center "Hera" EOOD [Recruiting] Montana, Bulgaria, 3400
	Medical Center Smolyan Clinical Research OOD [Recruiting] Smolyan, Bulgaria, 4700
	Medical Center Endomedical EOOD [Recruiting] Sofia, Bulgaria, 1606
	UMHAT Prof. Dr. Stoyan Kirkovich AD, Clinic of Cardiology [Recruiting] Stara Zagora, Bulgaria, 6000
	Medical Centre Nevromedics EOOD [Recruiting] Veliko Tarnovo, Bulgaria, 5006
	Canada, British Columbia
	Arc Biosystems [Recruiting] Vancouver, British Columbia, Canada, V6Z 2C7
	Canada, Ontario
	Canadian Phase Onward Inc [Recruiting] Toronto, Ontario, Canada, M3J 0K2
	Canada, Quebec
	Ecogene-21 [Recruiting] Chicoutimi, Quebec, Canada, G7H 7K9
	Institut de recherches cliniques de Montréal (IRCM) [Recruiting] Montréal, Quebec, Canada, H2W 1R7
	Clinique des Maladies Lipidiques de Quebec Inc. [Recruiting] Québec, Quebec, Canada, G1V 4W2
	Czechia
	MEDICUS SERVICES s.r.o. [Recruiting] Brandýs Nad Labem, Czechia, 250 01
	Interni Ambulance [Recruiting] Uherské Hradiště, Czechia, 686 01
	Denmark
	Esbjerg Hospital [Recruiting] Esbjerg, Denmark, 6700
	France
	CHU Dijon Bourgogne [Recruiting] Dijon, France, 21079
	Hopital de la Conception [Recruiting] Marseille, France, 13005
	Hungary
	CRU Hungary Kft [Recruiting] Borsod, Hungary, 3860
	Debreceni Egyetem Klinikai Kozpont Belgyogyaszat A epulet [Recruiting] Debrecen, Hungary, 4032
	DRC Gyogyszervizsgalo Kozpont Kft [Recruiting] Veszprém, Hungary, 8230
	Hungary, Heves
	BKS Research Kft [Recruiting] Hatvan, Heves, Hungary, 3000
	Hungary, Szabolcs-Szatmar-Bereg
	Medifarma 98 Kft [Recruiting] Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary, 4400
	Italy
	Ospdale E. Bassini [Recruiting] Milano, Italy, 20092
	A.O. Policlinico Universitario P. Giaccone [Recruiting] Palermo, Italy, 90127
	Policlinico Umberto [Recruiting] Roma, Italy, 00161
	Netherlands
	Rijnstate Arnhem [Recruiting] Arnhem, Netherlands, 6815 AD
	New Zealand
	New Zealand Clinical Research [Recruiting] Christchurch, New Zealand, 8011
	New Zealand, Auckland
	Auckland City Hospital [Recruiting] Grafton, Auckland, New Zealand, 1010
	Poland
	Salvia [Recruiting] Katowice, Poland, 40-772
	Praktyka Lekarska Ewa Krzyzagorska [Recruiting] Poznan, Poland, 61-655
	ClinMedica Research Sp.z o.o. [Recruiting] Skierniewice, Poland, 96-100
	Futuremeds sp. z o.o [Recruiting] Wroclaw, Poland, 50-088
	Instytut Centrum Zdrowia Matki Polki Klinika [Recruiting] Łódz, Poland, 93-338
	Portugal
	Hospital Egas Moniz - Centro Hospitalar de Lisboa Ocidental [Recruiting] Lisbon, Portugal, 1349-019
	South Africa
	University of Cape town - Lipid Factory [Recruiting] Cape Town, South Africa, 7925
	South Africa, Free State
	Iatros International [Recruiting] Bloemfontein, Free State, South Africa, 9301
	South Africa, Gauteng
	Unitas Hospital [Recruiting] Centurion, Gauteng, South Africa, 157
	South Africa, Western Cape
	Dr Jan Engelbrecht and Ass. Inc [Recruiting] Cape Town, Western Cape, South Africa, 7130
	TREAD Research - Department of Cardiology [Recruiting] Parow, Western Cape, South Africa, 7500
	Spain
	Hospital Abente y Lago [Recruiting] A Coruña, Spain, 15001
	Hospital de la Santa Creu i de Sant Pau [Recruiting] Barcelona, Spain, 08041
	Hospital Clinic Barcelona [Recruiting] Barcelona, Spain, 8063
	Institut d'Investigació i Innovació Parc Taulí (I3PT) Departament Medicina Universitat [Recruiting] Barcelona, Spain, 8208
	Hospital Universitari de Bellvitge [Recruiting] Barcelona, Spain, 8907
	Hospital Universitario Reina Sofia [Recruiting] Córdoba, Spain, 14004
	Hospital Universitario [Recruiting] Madrid, Spain, 28041
	Hospital Virgen del Rocio Edificio Centro de Diagnostico y Tratamiento (CDT) [Recruiting] Sevilla, Spain, 41013
	Sweden
	Karolinska University Hospital Huddinge [Recruiting] Stockholm, Sweden, 14186
	Sweden, Västra Götalands Län
	Sahlgrenska, University Hospital [Recruiting] Goteborg, Västra Götalands Län, Sweden, 413 45
	United Kingdom
	Hull Royal Infirmary [Recruiting] Hull, United Kingdom, HU3 2JZ
	United Kingdom, Huddersfield
	Huddersfield Royal Infirmary [Recruiting] Lindley, Huddersfield, United Kingdom, HD3 3EA

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: