Study of Tolerability and Efficacy of BVS857 in Severe Burn Subjects

Study Overview
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Brief Summary
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Study of tolerability and efficacy of BVS857 in severe burn subjects over 8 weeks and 15 weeks

Detailed Description
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No formal analysis was performed as study was terminated due to low enrollment issues. (n=1 patient was enrolled)

Official Title
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Multiple Ascending, Sequential, Placebo-controlled, Double-blind Study to Assess Safety, Tolerability and Efficacy of BVS857 in Severe Burn Subjects

Conditions
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Hypercatabolic Status Related to Severe Burn

Intervention / Treatment
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* Biological: BVS857
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Burn injury comprising 2nd degree deep partial thickness and/or 3rd degree full thickness burns, ≥20% total body surface area with expected need for surgical intervention and not exceeding the sum of age plus burn size of 100 (Baux score) Dosing must occur within 8-12 days post-burn Subjects must weigh at least 45kgs (for group 1 with doses of 0.03mg/kg) and be under 100 kg to participate in the study Exclusion Criteria: Spinal cord injury Hypoxic brain injury (Glasgow Coma Scale (GCS) <8) at screening True conductive electric burn with suspected neurologic injury Uncontrolled diabetes with HbA1c > 10% at screening, or known history of hypoglycemia, History of or active peripheral neuropathy or seizure disorder Systemic corticosteroids : > 10mg/d of prednisone or equivalent, other investigational treatments (excluding investigational dressings), medications for weight loss including megestrol acetate, androgens or oral beta agonists

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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No

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BVS857 Grp 1A open label<br>0.03 mg/kg of BVS857intravenously in open label manner | Biological: BVS857<br>* Group 1A&1B receive first dose as IV then remaining doses as SC. Groups 2, 3 and 4 receive only SC doses.<br>|
| Experimental: BVS857 Group 1B/1C, 2, 3, 4 Double Blind<br> | Biological: BVS857<br>* Group 1A&1B receive first dose as IV then remaining doses as SC. Groups 2, 3 and 4 receive only SC doses.<br>|
| Placebo Comparator: Placebo Group 1B/1C, 2, 3, 4<br> | Other: placebo<br>* Group 1B receive first dose as IV then remaining doses as SC. Groups 2, 3 and 4 receive only SC doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Number of patients with adverse events as a measure of safety and tolerability | Over 1 year | 
| Efficacy Measure by Change in Lean Body Mass (LBM) | Total LBM is measured by dual energy X-ray absorptiometry (DXA) scan. | Groups 2,3&4: Baseline, Day 35, Day 85 and Day 106 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Pharmacokinetics (PK) of BVS857: Cmax; The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: Tmax; The Time to Reach the Maximum Concentration After Drug Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: AUClast; The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: AUCinf; The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to Infinity |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: T1/2; The Terminal Elimination Half-life |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:ay D1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: CL; The Systemic (or Total Body) Clearance From Plasma (or Serum or Blood) Following Intravenous Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: Vz; The Volume of Distribution During the Terminal Elimination Phase Following Intravenous Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: Vss; The Volume of Distribution at Steady State Following Intravenous Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: Vz/F; The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 
| Serum Pharmacokinetics (PK) of BVS857: CL/F; The Apparent Systemic (or Total Body) Clearance From Plasma (or Serum or Blood) Following Extravascular Administration |  | Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burn, Severe burn, Lean body mass, Cachexia, Hypermetabolism, Catabolism, Wound healing