A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION547

A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION547 Administered Subcutaneously to Healthy Subjects

The purpose of this study is to evaluate the safety and tolerability of single and multiple doses of the antisense inhibitor ION547 administered subcutaneously (SC) in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ION547; Drug: Placebo

Detailed Description

This is a Phase 1, double-blind, randomized, placebo-controlled, dose escalation study of ION547 in up to 76 participants. Participants will be randomized to receive single and multiple doses of ION547 or placebo SC. The maximum length of participation in the study will be approximately 34 weeks.

• Study Type: Interventional
• Enrollment (Actual): 48
• 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
2. Healthy males or females 18 to 65, inclusive, at the time of informed consent.

3. Satisfy the following:

   a. Females: Women of childbearing potential are not allowed to participate in this study.

4. b. Males must be abstinent, surgically sterile (vasectomy with negative semen analysis at Follow-up, or a surgically sterile non-pregnant female partner) or if engaged in sexual relations with a woman of childbearing potential (WOCBP), participant is utilizing a highly effective contraceptive method
5. Body mass index (BMI) ≤ 35 kilograms per square meter (kg/m^2).

Exclusion Criteria:

1. Clinically significant abnormalities in medical history or physical examination.

2. Screening laboratory results as follows, or any other clinically significant (CS) abnormalities in screening laboratory values that would render a participant unsuitable for inclusion:

   1. Urine protein/creatinine (P/C) ratio greater than or equal to (≥) 0.2 milligrams (mg)/mg.
   2. Positive test (including trace) for blood on urinalysis.
   3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, and blood urea nitrogen (BUN) > upper limit of normal (ULN).
   4. Hemoglobin A1c (HbA1c) > ULN
   5. Platelet count < lower limit of normal (LLN)
   6. aPTT > ULN
   7. INR > 1.4
   8. Evidence of uncorrected hypothyroidism or hyperthyroidism based on thyroid function results at Screening.
3. Uncontrolled hypertension (blood pressure [BP] > 160/100 millimeters of mercury [mmHg]).
4. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
5. Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer.
6. Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of screening if single dose received, or within 12 months of screening if multiple doses received. Exclusion does not apply to Covid-19 messenger ribonucleic acid (mRNA) vaccines.
7. History of bleeding diathesis or coagulopathy.
8. Regular use of alcohol within 6 months prior to screening (> 7 drinks/week for females, > 14 drinks/week for males [1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor]), or use of soft drugs (such as marijuana) within 3 months prior to screening, or hard drugs (such as cocaine and phencyclidine [PCP]) within 1 year prior to screening, or positive urine drug screen at Screening.
9. Concomitant medication restrictions: the use of prescription and over-the-counter medications including nonsteroidal anti-inflammatory drugs (with the exception of occasional acetaminophen or ibuprofen) and herbal remedies at Screening and throughout the Study Period.
10. Smoking limitations: more than 10 cigarettes/day at Screening and those with a significant change in smoking habits within 1 month prior to Screening should be excluded.
11. 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: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ION547; Ascending single multiple doses of ION547 will be administered by SC injection.	Drug: ION547; ION547 will be administered by SC injection.
Placebo Comparator: Placebo; Ascending single multiple doses of ION547-matching placebo will be administered by SC injection.	Drug: Placebo; ION547-matching placebo 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 232
Cmax: Maximum Observed Plasma Concentration of ION547	Up to Day 232
Tmax: Time Taken to Reach Maximal Plasma Concentration of ION547	Up to Day 232
AUCt: Area Under the Plasma Concentration-time Curve From Time Zero to Time t for ION547	Up to Day 232
Urine 0-24 Hour (hr) Excretion of ION547	Up to 24 hours
Change from Baseline in FXII Antigen Levels	Up to Day 232
Change from Baseline in FXII Activity Levels	Up to Day 232

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): September 14, 2022
• Study Completion (Actual): September 14, 2022

Study Registration Dates

• First Submitted: June 8, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Participants
• Other Study ID Numbers: ION547-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
• product manufactured in and exported from the U.S.: Yes