Study of Tolerability and Efficacy of BVS857 in Severe Burn Subjects

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

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

Study Overview

• Status: Terminated
• Conditions: Hypercatabolic Status Related to Severe Burn
• Intervention / Treatment: Biological: BVS857; Other: placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: February 27, 2014
• First Submitted That Met QC Criteria: February 27, 2014
• First Posted (Estimate): March 3, 2014

Study Record Updates

• Last Update Posted (Estimate): March 7, 2016
• Last Update Submitted That Met QC Criteria: March 3, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Burn, Severe burn, Lean body mass, Cachexia, Hypermetabolism, Catabolism, Wound healing
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns
• Other Study ID Numbers: CBVS857X2201