Study of DTRI-031 in Healthy Volunteers

Study Overview
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Brief Summary
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A randomized, double-blind, single center, placebo-controlled phase 1 study in healthy volunteers to assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous (iv) injection of DTRI-031

Detailed Description
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Up to 5 cohorts of 8 healthy volunteers for a total of 40 volunteers will be randomized to either DTRI-031 or matching placebo (6 active:2 placebo). Two sentinel subjects, one randomized to each group, will be dosed at least 1 day prior to dosing of the remaining subjects in a cohort. Subjects will complete a screening visit up to 28 days prior to administration of study drug to confirm eligibility. Eligible subjects will arrive at the phase 1 unit up to 24 hours prior to Day 1 and remain until completion of 24-hour assessments. Subjects will return for a Day 7 follow-up visit and receive a safety assessment telephone call on Day 28. A Safety Review Committee will review individual subject and aggregate group safety data following each dose-based study cohort and recommend whether the trial should continue to the next cohort.

Official Title
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A Randomized, Double-Blind, Single-Center, Placebo-Controlled Phase 1 Study to Evaluate the Safety, Tolerability, PK and PD of Intravenous DTRI-031 in Healthy Volunteers

Conditions
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Healthy Volunteers, Pharmacokinetics, Pharmacodynamics

Intervention / Treatment
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* Drug: DTRI-031
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-55 years of age Ability to provide written consent Weight 50-110 kg with BMI 18.5-32 kg/m2 Willingness to use contraceptives Negative COVID-19 test Negative results for alcohol and drugs of abuse Exclusion Criteria: Pregnant or lactating females Familial bleeding disorder or individual or family history of bleeding diathesis or coagulopathy Females with active menstruation on day of dosing Use of prescription medications known to affect platelet function Use of NSAIDs, aspirin, anti-platelet or anti-coagulation therapy within 10 days of dosing Contraindication to anticoagulation or increased bleeding risks History of thrombocytosis, high platelet count, intracranial bleeding, aneurysm, stroke, vascular disease History of peptic ulcer disease, gastrointestinal or genitourinary bleed, severe trauma, fracture, major surgery of biopsy of parenchymal organ within past 3 months Planned surgery during the study Any clinical significant abnormality at screening Use of investigational drug in past 30 days or 5 half lives Concurrent enrollment in another clinical study or more than 3 clinical studies in past 12 months Any prior history of substance abuse or treatment or positive urine screen for drugs of abuse or positive breathalyzer test

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Parallel Assignment
Interventional Model Description: Randomized, placebo-controlled, double-blinded, dose escalation to evaluate the safety, PK, and PD of a single dose of investigational drug or placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Comparator: Single ascending dose DTRI-031<br>Drug: DTRI-031 Single doses of DTRI-031 delivered via intravenous injection. Ascending dose levels will be evaluated. | Drug: DTRI-031<br>* Investigational drug<br>|
| Placebo Comparator: Placebo Comparator: Single Dose Placebo<br>Drug: Placebo Single doses of placebo delivered via intravenous injection, matched to DTRI-031 cohorts | Drug: Placebo<br>* Matching placebo to DTRI-031<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by adverse events (AEs) | Incidence of treatment-emergent AEs | From dosing (DTRI-031 or placebo) to final visit (Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics as measured by DTRI-031 plasma levels | Plasma concentration of DTRI-031 (after single dose of drug) | From dosing to 24 hours after dosing | 
| Plasma von Willebrand Factor (vWF) levels | Level of vWF following single administration of drug | From dosing to 24 hours after dosing | 
| Platelet Function | Whole blood platelet function closure times | From dosing to 24 hours after dosing |