Healthy Participants
Conditions
Keywords
IONIS FXI-L, Factor XI
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.
Interventions
DRUGIONIS FXI-LRx
Ascending single and multiple doses of IONIS FXI-LRx by subcutaneous (SC) injection
DRUGPlacebo
Sterile Normal Saline (0.9% NaCl) calculated volume to match active comparator
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability as Measured by the Number of Participants with Treatment-Emergent Adverse Events | Up to 232 Days |
Secondary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Factor XI antigen levels | Up to 232 Days | Factor XI antigen levels will be measured with a reference range of 0.72-1.63 U/mL |
| Change from Baseline in the international normalized ratio (INR) | Up to 232 Days | — |
| Change from Baseline in Factor XI activity levels | Up to 232 Days | Factor XI activity levels will be measured with a reference range of 0.73-1.45 U/mL |
| Change from Baseline in activated partial thromboplastin time (aPTT) | Up to 232 Days | — |
| Change from Baseline in prothrombin time (PT) | Up to 232 Days | — |
Countries
Canada
Outcome results
None listed