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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03582462
Recruitment Status : Completed
First Posted : July 11, 2018
Last Update Posted : January 18, 2022
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Healthy Participants Drug: IONIS FXI-LRx Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : July 9, 2018
Actual Primary Completion Date : April 26, 2019
Actual Study Completion Date : April 26, 2019

Arm Intervention/treatment
Experimental: IONIS FXI-LRx
Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection.
Drug: IONIS FXI-LRx
Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection

Placebo Comparator: Placebo
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator.
Drug: Placebo
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator




Primary Outcome Measures :
  1. Safety and Tolerability as Measured by the Number of Participants with Treatment-Emergent Adverse Events [ Time Frame: Up to 232 Days ]

Secondary Outcome Measures :
  1. Cmax: maximum observed drug concentration in plasma of IONIS FXI-LRx [ Time Frame: Up to 232 Days ]
  2. Tmax: time taken to reach maximal concentration in plasma of IONIS FXI-LRx [ Time Frame: Up to 232 Days ]
  3. AUC: area under the plasma concentration time curve for IONIS FXI-LRx [ Time Frame: Up to 232 Days ]

Other Outcome Measures:
  1. Change from Baseline in Factor XI antigen levels [ Time Frame: Up to 232 Days ]
    Factor XI antigen levels will be measured with a reference range of 0.72-1.63 U/mL

  2. Change from Baseline in Factor XI activity levels [ Time Frame: Up to 232 Days ]
    Factor XI activity levels will be measured with a reference range of 0.73-1.45 U/mL

  3. Change from Baseline in activated partial thromboplastin time (aPTT) [ Time Frame: Up to 232 Days ]
  4. Change from Baseline in prothrombin time (PT) [ Time Frame: Up to 232 Days ]
  5. Change from Baseline in the international normalized ratio (INR) [ Time Frame: Up to 232 Days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03582462


Locations
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Canada, Ontario
BioPharma Services Inc.
Toronto, Ontario, Canada, M9L #A2
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03582462    
Other Study ID Numbers: ION 957943-CS1
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: January 18, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Ionis Pharmaceuticals, Inc.:
IONIS FXI-L
Factor XI