Study of VGA039 in Healthy Volunteers and Patients With Von Willebrand Disease

Study Overview
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Brief Summary
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This is a multi-center, Phase 1a study to assess the safety, tolerability, PK, and PD of VGA039 following single IV or SC dose administration in healthy subjects and Von Willebrand disease patients.

Detailed Description
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This first in human study consists of 2 parts based on the subject population: Part 1 and Part 2. Part 1 is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) evaluation of IV or SC VGA039 or placebo in up to 8 cohorts. Part 2 is an open-label, SAD of SC and IV VGA039 in up to 8 cohorts. All participants will be enrolled, treated, and followed up for 15 weeks (IV SAD) or 8 weeks(SC SAD).

Official Title
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A Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of VGA039 Following IV or SC Administration of Single Ascending Doses in Healthy Adults and Subcutaneous Adult Patients With Von Willebrand Disease

Conditions
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Von Willebrand Diseases

Intervention / Treatment
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* Drug: VGA039
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria (All Subjects) Subjects, 18 to 60 years of age, inclusive. No clinically significant laboratory, ECG, or vital signs results. Additional Key Inclusion Criteria (for Subjects in Part 1 Only) • Body mass index of 18-32 kg/m2 Additional Key Inclusion Criteria (for Subjects in Part 2 Only) Subjects with VWD who are symptomatic, defined as having a history of bleeding or bruising. Hemoglobin level ≥ 8 g/dL and platelet count ≥ 150 × 109/L at Screening. Exclusion Key Criteria (All Subjects) Use of hormonal contraceptives within 56 days prior to administration of the study drug. Subjects with detection of FV Leiden or Prothrombin G20210A mutation, protein C or S deficiency, antithrombin deficiency, or antiphospholipid antibody syndrome at Screening. Subjects with other known pro-thrombotic disorders or abnormal findings in any prior laboratory thrombophilia evaluation. History of arterial or venous thrombosis, including superficial thrombophlebitis, or embolism. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, or metabolic dysfunction. Additional Key Exclusion Criterion (Subjects in Part 1 Only) • Baseline FVIII activity > 150 IU/dL. Additional Key Exclusion Criteria (Subjects in Part 2 Only) Baseline FVIII activity > 50 IU/dL. Any acute, clinically significant bleeding event requiring surgical or procedural intervention within 7 days prior to receiving study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part 1<br>Cohorts 1-8 IV or SC VGA039 or Placebo dose to be determined | Drug: VGA039<br>* Single doses of VGA039<br>Other: Placebo<br>* Single doses of Placebo<br>|
| Experimental: Part 2<br>Cohorts A-H IV or SC VGA039 dose to be determined | Drug: VGA039<br>* Single doses of VGA039<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] | Incidence, nature and severity of adverse events (AEs) and serious adverse events (SAEs), including dose-limiting toxicities (DLTs). | From start of study drug administration until 15 or 8 weeks after IV or SC study drug administration, respectively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentrations of single IV and SC doses of VGA039 |  | From baseline until 15 or 8 weeks after IV or SC study drug administration, respectively | 
| Pharmacodynamics of single IV and SC doses of VGA039 |  | From baseline until 15 or 8 weeks after IV or SC study drug administration, respectively | 
| Incidence of Anti-drug antibodies to VGA039 |  | From baseline until 15 or 8 weeks after IV or SC study drug administration, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Von Willebrand Disorder