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

• Sponsor: Ionis Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04731623
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.5
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: ION904; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Feb 26, 2021
• Actual Primary Completion Date: Aug 12, 2021
• Actual Study Completion Date: Sep 11, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) [Up to Day 85]

2. Severity and dose relationship of TEAE [Up to Day 85]

3. Severity and dose relationship of clinically significant changes in laboratory values [Up to Day 85]

4. Severity and dose relationship of clinically significant changes in ECG [Up to Day 85]

Secondary Outcome Measures

1. Changes in the Level of ION904 Target Biomarker [Up to Day 85]

2. Cmax: Maximum Observed Plasma Concentration of ION904 [Up to Day 85]

3. Tmax: Time to Reach the Maximum Plasma Concentration of ION904 [Up to Day 85]

4. t½λz: Plasma Elimination Half-life of ION904 [Up to Day 85]

5. AUC0-t: Area Under the Plasma Concentration-Time Curve from Time Zero to Time t for ION904 [Up to Day 85]

6. Urine 0-24 Hour (hr) Excretion of ION904 [Up to 24 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

1. Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BioPharma Services, Inc.	Toronto	Ontario	Canada	M9L 3A2

Sponsors and Collaborators

• Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ionis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04731623
• Other Study ID Numbers: ION904-CS1
• First Posted: Feb 1, 2021
• Last Update Posted: Aug 9, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ionis Pharmaceuticals, Inc.: Healthy Participants; Hypertension

Study Results

No Results Posted as of Aug 9, 2022