A Study Comparing Two Subcutaneous Formulations: Vial and Autoinjector (AI) With Olezarsen, at Two Dose Levels, in Healthy Adult Participants

A Single-Dose, Randomized, Open-Label, Two-Period Crossover, Bioequivalence Study Comparing Two Subcutaneous Formulations: Vial and Autoinjector (AI) With Olezarsen, at Two Dose Levels, in Healthy Adult Participants

The purpose of the study is to assess the bioequivalence of olezarsen between 2 subcutaneous (SC) formulations [(autoinjector (AI) and vial] at 2 dose levels in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Olezarsen

Detailed Description

This is a Phase 1, single-dose, randomized, open-label, two-period, crossover study in approximately 100 healthy participants. The study will consist of an up to 28-day Screening Period, two treatment periods of 15 days each - with the second treatment period starting 28-42 days after the first begins - and a Post-Treatment Follow-Up Period lasting 91 days after the second treatment period begins. Eligible participants will be randomized to two dose groups (50 mg or 80 mg olezarsen). Participants will be dosed once at the beginning of each treatment period, one time using a single-use AI and one time using a single-use vial. Within each dose group, approximately half of the participants will be dosed with the AI first, with the other participants being dosed with the vial first.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Medpace Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Must have given written informed consent (signed and dated) and any authorizations required by local law, be able to comply with all study requirements prior to receiving any study drug, and be able to communicate effectively with clinic staff
2. Must be a healthy, adult male or female, 18 to 64 years of age (inclusive), and non-smoking (for at least 6 months prior to first study drug administration)
3. Females must be of non-childbearing potential

Exclusion Criteria:

1. Have a known history or presence of any clinically significant hepatic (e.g., hepatic impairment), renal/genitourinary (e.g., renal impairment), gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological, or hematological disease or condition unless determined as not clinically significant by the PI/sub-investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olezarsen Dose Level 1; Participants will receive two doses of Dose Level 1 each, using one of the following two sequences: (i) AI on Day 1 of Treatment Period 1, followed by vial on Day 1 of Treatment Period 2; or (ii) vial on Day 1 of Treatment Period 1, followed by AI on Day 1 of Treatment Period 2. A washout period of 28-42 days will be maintained between the 2 treatment periods.	Drug: Olezarsen; Olezarsen will be administered by SC injection.; Other Names: ISIS 678354
Experimental: Olezarsen Dose Level 2; Participants will receive two doses of Dose Level 2 each, using one of the following two sequences: (i) AI on Day 1 of Treatment Period 1, followed by vial on Day 1 of Treatment Period 2; or (ii) vial on Day 1 of Treatment Period 1, followed by AI on Day 1 of Treatment Period 2 A washout period of at least 28 days will be maintained between the 2 treatment periods.	Drug: Olezarsen; Olezarsen will be administered by SC injection.; Other Names: ISIS 678354

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration-time curve (AUC) of olezarsen from time 0 to 336 hours (AUC0-336h)	Up to Day 8 of each of Treatment Periods 1 and 2
Maximum plasma concentration of olezarsen (Cmax)	Up to Day 91 of Treatment Period 2

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Actual): May 22, 2023
• Study Completion (Actual): May 22, 2023

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ISIS 678354-CS20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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