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

NCT03582462 | Completed Phase 1 FDA Drug

• 1 other identifier: ION 957943-CS1
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Keywords

IONIS FXI-L; Factor XI

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability as Measured by the Number of Participants with Treatment-Emergent Adverse Events

  Up to 232 Days

Secondary Outcomes (3)

• Cmax: maximum observed drug concentration in plasma of IONIS FXI-LRx

  Up to 232 Days

• Tmax: time taken to reach maximal concentration in plasma of IONIS FXI-LRx

  Up to 232 Days

• AUC: area under the plasma concentration time curve for IONIS FXI-LRx

  Up to 232 Days

Other Outcomes (5)

• Change from Baseline in Factor XI antigen levels

  Up to 232 Days

• Change from Baseline in Factor XI activity levels

  Up to 232 Days

• Change from Baseline in activated partial thromboplastin time (aPTT)

  Up to 232 Days

Study Arms (2)

IONIS FXI-LRx

EXPERIMENTAL

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

Drug: IONIS FXI-LRx

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

IONIS FXI-LRx DRUG

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

IONIS FXI-LRx

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (1)

BioPharma Services Inc.

Toronto, Ontario, M9L #A2, Canada

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: July 11, 2018
• Study Start: July 9, 2018
• Primary Completion: April 26, 2019
• Study Completion: April 26, 2019
• Last Updated: January 18, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)