A Study to Evaluate Plasma Gelsolin in Healthy Volunteers

Study Overview
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Brief Summary
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Study BTI-101 is a Phase 1, randomized, double-blind, placebo-controlled, dose escalation, parallel design study to evaluate the safety, tolerability, and pharmacokinetics of IV rhu-pGSN or saline placebo administered as 5 doses each of 6, 12, 18, or 24 mg/kg of body weight. Each of 4 dosing cohorts will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects). Subjects will be healthy adult volunteers 18-55 years of age.

Detailed Description
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Doses will be administered at 0 hours (Day 1), 12 hours (Day 1), 36 hours (Day 2), 60 hours (Day 3), and 84 hours (Day 4). Subjects will be kept in-house until after the last blood sample is taken on Day 5. Subjects will return for follow-up 7 days after the initiation of therapy (Day 8) and on Day 28 for the End-of-Study (EOS) Visit. After each cohort has completed the Day 8 visit, review of the safety results (including labs) will be conducted (and unblinded where appropriate) before the initiation of the next higher dose cohort. To assess safety and tolerability, subjects will undergo physical examinations (including vital sign measurements), adverse event (AE) assessments, concomitant medication assessments, and safety laboratory testing. Blood samples will be collected for analysis of pGSN levels and antibodies against pGSN.

Official Title
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Single-center, Randomized, Double-blind, Placebo-controlled, Ascending-Dose Study to Evaluate the Safety and Pharmacokinetics of Recombinant Human Plasma Gelsolin (Rhu-pGSN) After Intravenous Administration to Healthy Volunteers

Conditions
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Volunteers, Healthy

Intervention / Treatment
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* Drug: Recombinant human plasma gelsolin
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female adults 18 to 55 years of age without chronic or active acute medical conditions Informed consent obtained from subject Weight ≤100 kg and body mass index (BMI) <30 kg/m2 Willingness to use contraception during the course of the study, starting at screening and for at least 3 months after their final study treatment Exclusion Criteria: Pregnant or lactating women Acute illness during the month prior to screening Circumstances that may require any medications (including prescription medication, over-the-counter medication, vitamins, or supplements) during the during the inpatient days of the study other than acetaminophen Hospitalization during the year prior to screening History of cancer or treatment with systemic chemotherapy or radiation therapy at any time Transplantation of hematopoietic or solid organs History of diabetes mellitus; myocardial infarction, angina, or other cardiovascular disease; stroke or cerebrovascular disease; chronic obstructive pulmonary disease (COPD) or asthma; deep vein thrombosis (DVT)/pulmonary embolism (PE); liver or kidney disease; clinically significant psychiatric condition; or active or chronic infection Receipt of blood products during the year prior to screening Chronic mechanical ventilation or dialysis Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the Investigator Any clinically significant abnormalities of vital signs, EKG or physical examination findings as judged by the Investigator Positive results for recreational drugs during screening Any other condition deemed by the Investigator as possibly interfering with the conduct of the study

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhu-pGSN<br>Treated with 5 doses of rhu-pGSN | Drug: Recombinant human plasma gelsolin<br>* intravenous administration of either 6, 12, 18, or 24 mg/kg at time 0, 12, 36, 60 and 84 hours<br>|
| Placebo Comparator: normal saline<br>Treated with 5 doses of saline | Other: placebo<br>* intravenous administration of saline control at time 0, 12, 36, 60 and 84 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety -- SAE frequency | serious adverse events | 28 days | 
| Safety -- severe AE frequency | Grade 3/4 severe adverse events | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics -- pGSN levels over time after dosing | pGSN levels | 108 hours | 
| antidrug antibodies -- frequency before and 28 days post-dose | anti-pGSN antibodies | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, pharmacokinetics