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

Ionis Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Healthy Participants

Treatments

Drug: IONIS FXI-LRx

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT03582462

ION 957943-CS1

Details and patient eligibility

About

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.

Full 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.

Enrollment

66 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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)