A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of IONIS FXI-LRx in up to 84 Healthy Volunteers

NCT ID: NCT03582462

Last Updated: 2022-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-09
• Study Completion Date: 2019-04-26

Brief Summary

To evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics, including Factor XI activity and antigen levels, activated partial thromboplastin time, prothrombin time and international normalized ratio of single and multiple doses of Factor XI antisense inhibitor administered subcutaneously to healthy volunteers.

Detailed Description

This will be a Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study conducted at a single center. The study consists of 4 escalating single-dose cohorts (n = 8 per cohort, randomized 3 IONIS FXI-LRx active:1 placebo), 3 escalating multiple-dose cohorts with weekly Study Drug (IONIS FXI-LRx or placebo) administration for 8 healthy volunteers per cohort, randomized 3 active:1 placebo, and 1 multiple-dose cohort of 10 healthy volunteers randomized 3 active:2 placebo with Study Drug administration every 4 weeks.

Approximately 66 healthy volunteers are planned to be enrolled in this study. Additional healthy volunteers may be added to better assess the safety, tolerability or pharmacokinetic profile of IONIS FXI-LRx to meet study objectives.

Conditions

Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IONIS FXI-LRx

Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection.

Group Type: EXPERIMENTAL

IONIS FXI-LRx

Intervention Type: DRUG

Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection

Placebo

Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator

Interventions

IONIS FXI-LRx

Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection

Intervention Type: DRUG

Placebo

Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI) ≤ 35 kg/m2
• Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
• Males must be surgically sterile, abstinent or, if engaged in sexual relations with a female of child-bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug
• Willing to refrain from strenuous exercise/activity for at least 72 hrs prior to study visits
• Must abstain from alcoholic beverages for at least 48 hrs prior to clinic visits and not increase alcohol consumption during the study

Exclusion Criteria

• Clinically-significant abnormalities in medical history, screening laboratory results, physical examination that would render a subject unsuitable for inclusion. Including but not limited to:

• Platelet count < LLN
• INR > 1.4
• aPTT > ULN
• FXI activity < 0.7 U/mL
• Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
• Any history of previous treatment with an oligonucleotide
• History of bleeding diathesis or coagulopathy
• Uncontrolled hypertension (BP > 160/100 mm Hg)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

BioPharma Services Inc.

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

ION 957943-CS1

Identifier Type: -

Identifier Source: org_study_id