A Study to Assess the Safety, Tolerability and Efficacy of ION775

A Phase 2, Open-label Trial Evaluating the Safety, Tolerability and Efficacy of ION775 in Adults With Hypertriglyceridemia

The main objective of this study is to evaluate the effect of ION775 on fasting triglyceride (TG) levels in participants with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (sHTG).

Study Overview

• Status: Recruiting
• Conditions: Hypertriglyceridemia; Severe Hypertriglyceridemia
• Intervention / Treatment: Drug: ION775

Detailed Description

This is an open-label, parallel-dose study consisting of a 4-6 week screening period, a 6-month treatment period and a 6-month post-treatment follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals, Inc.; Phone Number: 1-844-828-3770; Email: IonisION775-CS2@clinicaltrialmedia.com

Study Locations

• United States
  • California
    • Lincoln, California, United States, 95648
      • Recruiting
      • Ionis Investigative Site
  • Florida
    • Miami, Florida, United States, 33184
      • Recruiting
      • Ionis Investigative Site
    • Miramar, Florida, United States, 33027
      • Recruiting
      • Ionis Investigative Site
  • Michigan
    • Flint, Michigan, United States, 48504
      • Recruiting
      • Ionis Investigative Site
  • Ohio
    • Munroe Falls, Ohio, United States, 44262
      • Recruiting
      • Ionis Investigative Site
  • South Carolina
    • Little River, South Carolina, United States, 29566
      • Recruiting
      • Ionis Investigative Site
  • Texas
    • Lampasas, Texas, United States, 76550
      • Recruiting
      • Ionis Investigative Site
    • San Antonio, Texas, United States, 78209
      • Recruiting
      • Ionis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Adult males and females with HTG (fasting TG more than or equal to (≥) 350 milligrams per deciliter (mg/dL) [3.95 millimoles per liter (mmol/L)] or with sHTG (fasting TG ≥ 500 mg/dL [5.65 mmol/L]).
2. Participants should be on standard of care lipid-lowering medications per local guidelines.

Key Exclusion Criteria:

1. Hemoglobin A1c (HbA1c) ≥ 8.5% at Screening.
2. Alanine aminotransferase or aspartate aminotransferase > 2.0 × upper limit of normal.
3. Total bilirubin > 1.5 upper limit of normal unless due to Gilbert's syndrome.
4. Estimated GFR < 30 mL/min/1.73 m^2.

Note: Other protocol pre-specified inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ION775: Cohot A; Participants will be randomized to receive ION775 by subcutaneous (SC) injection.	Drug: ION775; ION775 will be administered by SC injection.
Experimental: ION775: Cohot B; Participants will be randomized to receive ION775 by SC injection.	Drug: ION775; ION775 will be administered by SC injection.
Experimental: ION775: Cohot C; Participants will be randomized to receive ION775 by SC injection.	Drug: ION775; ION775 will be administered by SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline in Fasting Triglyceride (TG)	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With at Least One Treatment-Emergent Adverse Events (TEAEs)	Up to 12 Months
Number of Participants who Experience Abnormalities in Clinical Laboratory Evaluations	Up to 12 Months
Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III)	Baseline, Month 6
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C)	Baseline, Month 6
Percent Change From Baseline in Remnant Cholesterol When Directly Measured	Baseline, Month 6
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C)	Baseline, Month 6

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Hypertriglyceridemia
• Other Study ID Numbers: ION775-CS2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No