A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION904

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending, Dose-Escalation, Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION904 Administered Subcutaneously to Healthy Participants

The purpose of this study is to assess the safety and tolerability of ION904.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ION904; Drug: Placebo

Detailed Description

This is a Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose escalation study of ION904 in up to 72 participants. Following a Screening Period of up to 28 days, eligible healthy participants will be randomized to treatment and receive a single, subcutaneous (SC) dose of the assigned study drug. Participants will be followed for up to 13 weeks after dosing.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M9L 3A2
      • BioPharma Services, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must be healthy males, or females of non-childbearing potential, aged 18 to 65 at the time of informed consent
2. Females must be either surgically sterile or post-menopausal; males must be abstinent, surgically sterile, or if engaged in sexual relations with a woman of childbearing potential, a highly effective contraceptive method must be used from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug or the healthy participant must be abstinent through this time period
3. Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 24 hours prior to study visits
4. Body mass index (BMI) requirements between 18 and 35 kg/m^2

Exclusion Criteria:

1. Clinically significant abnormalities in medical history or physical examination
2. Uncontrolled arterial hypertension
3. Active infection with human immunodeficiency virus (HIV), hepatitis C or hepatitis B or prior treatment for hepatitis C
4. Treatment with another investigational drug, biological agent, or device within 1 month of Screening
5. History of bleeding diathesis or coagulopathy
6. Regular use of alcohol within 6 months prior to screening, or use of soft drugs within 3 months prior to Screening, or hard drugs within 1 year prior to Screening, or positive urine drug screen at Screening
7. History of any severe (e.g., anaphylaxis) drug allergies
8. History of hypersensitivity to other antisense oligonucleotides (ASOs)

9. Concomitant medication restrictions: over-the-counter or prescription medications within 14 days, prior to dosing on Day 1. Accepted exceptions are:

   • Acetaminophen (paracetamol) up to 2 grams per day (g/d) or ibuprofen up to 2.4 g/day taken sporadically for analgesia
   • Thyroid hormone replacement therapy provided participant is stable on replacement therapy (and participant is euthyroid)
   • Other possible exceptions must be reviewed and acknowledged by the Investigator in consultation with Sponsor's Medical Monitor
10. Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ION904; Single ascending dose of ION904 will be administered by SC injection on Day 1.	Drug: ION904; ION904 will be administered by SC injection.
PLACEBO_COMPARATOR: Placebo; Placebo (0.9% sterile saline) will be administered by SC injection on Day 1.	Drug: Placebo; Placebo (0.9% sterile saline) will be administered by SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	Up to Day 85
Severity and dose relationship of TEAE	Up to Day 85
Severity and dose relationship of clinically significant changes in laboratory values	Up to Day 85
Severity and dose relationship of clinically significant changes in ECG	Up to Day 85

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in the Level of ION904 Target Biomarker	Up to Day 85
Cmax: Maximum Observed Plasma Concentration of ION904	Up to Day 85
Tmax: Time to Reach the Maximum Plasma Concentration of ION904	Up to Day 85
t½λz: Plasma Elimination Half-life of ION904	Up to Day 85
AUC0-t: Area Under the Plasma Concentration-Time Curve from Time Zero to Time t for ION904	Up to Day 85
Urine 0-24 Hour (hr) Excretion of ION904	Up to 24 hours

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 26, 2021
• Primary Completion (ACTUAL): August 12, 2021
• Study Completion (ACTUAL): September 11, 2021

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (ACTUAL): February 1, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 6, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Hypertension; Healthy Participants
• Other Study ID Numbers: ION904-CS1

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