History of Changes for Study: NCT05079919

A Study of ISIS 678354 Administered to Participants With Severe Hypertriglyceridemia

Latest version (submitted May 10, 2024) on ClinicalTrials.gov

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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

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Study NCT05079919
Submitted Date: February 18, 2022 (v6)

Study Identification


Unique Protocol ID:	ISIS 678354-CS5
Brief Title:	A Study of 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:	February 2022
Overall Status:	Recruiting
Study Start:	October 25, 2021
Primary Completion:	July 2024 [Anticipated]
Study Completion:	July 2024 [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:	February 18, 2022
Last Update Posted:	February 21, 2022 [Actual]

Study Description

Brief Summary:

The purpose of the study is to evaluate the efficacy of ISIS 678354 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 450 participants. Participants will be randomized to receive ISIS 678354 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

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Double (Participant, Investigator)
Allocation:	Randomized
Enrollment:	450 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: ISIS 678354 ISIS 678354 will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.	Drug: ISIS 678354 ISIS 678354 will be administered by SC injection. Other Names: AKCEA-APOCIII-LRx
Placebo Comparator: Placebo ISIS 678354-matching placebo will be administered once every 4 weeks by SC injection from Week 1 through Week 49.	Drug: Placebo ISIS 678354-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 23, 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 should be on standard of care lipid-lowering medications per local guidelines unless intolerant. 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 Platelet count < 100K/cubic millimeters at Screening or Qualification 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 < 40 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
	America Clinical Trials [Recruiting] Tarzana, California, United States, 91356
	United States, Florida
	Excel Medical Clinical Trials, LLC [Recruiting] Boca Raton, Florida, United States, 33434
	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, Michigan
	Aa Mrc, Llc [Recruiting] Flint, Michigan, United States, 48504
	United States, Ohio
	Summit Research Group, LLC [Recruiting] Munroe Falls, Ohio, United States, 44262
	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, Virginia
	Manassas Clinical Research Center [Recruiting] Manassas, Virginia, United States, 20110
	York Clinical Research LLC [Recruiting] Norfolk, Virginia, United States, 23510

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