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

Healthy Participants Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of ION-957943 (IONIS FXI-LRX, a GalNAc Conjugated 2'-MOE Chimeric Antisense Oligonucleotide Inhibitor of Factor XI) Administered Subcutaneously to Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03582462
• Other study ID #: ION 957943-CS1
• Status: Completed
• Phase: Phase 1
• Start date: July 9, 2018
• Est. completion date: April 26, 2019

Study information

• Verified date: January 2022
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: April 26, 2019
• Est. primary completion date: April 26, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• IONIS FXI-LRx
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

Locations

Country	Name	City	State
Canada	BioPharma Services Inc.	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from Baseline in Factor XI antigen levels	Factor XI antigen levels will be measured with a reference range of 0.72-1.63 U/mL	Up to 232 Days
Other	Change from Baseline in Factor XI activity levels	Factor XI activity levels will be measured with a reference range of 0.73-1.45 U/mL	Up to 232 Days
Other	Change from Baseline in activated partial thromboplastin time (aPTT)		Up to 232 Days
Other	Change from Baseline in prothrombin time (PT)		Up to 232 Days
Other	Change from Baseline in the international normalized ratio (INR)		Up to 232 Days
Primary	Safety and Tolerability as Measured by the Number of Participants with Treatment-Emergent Adverse Events		Up to 232 Days
Secondary	Cmax: maximum observed drug concentration in plasma of IONIS FXI-LRx		Up to 232 Days
Secondary	Tmax: time taken to reach maximal concentration in plasma of IONIS FXI-LRx		Up to 232 Days
Secondary	AUC: area under the plasma concentration time curve for IONIS FXI-LRx		Up to 232 Days