Hypercatabolic Status Related to Severe Burn
Conditions
Keywords
Burn, Severe burn, Lean body mass, Cachexia, Hypermetabolism, Catabolism, Wound healing
Brief summary
Study of tolerability and efficacy of BVS857 in severe burn subjects over 8 weeks and 15 weeks
Detailed description
No formal analysis was performed as study was terminated due to low enrollment issues. (n=1 patient was enrolled)
Interventions
BIOLOGICALBVS857
Group 1A&1B receive first dose as IV then remaining doses as SC. Groups 2, 3 and 4 receive only SC doses.
OTHERplacebo
Group 1B receive first dose as IV then remaining doses as SC. Groups 2, 3 and 4 receive only SC doses.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Over 1 year | Number of patients with adverse events as a measure of safety and tolerability |
| Efficacy Measure by Change in Lean Body Mass (LBM) | Groups 2,3&4: Baseline, Day 35, Day 85 and Day 106 | Total LBM is measured by dual energy X-ray absorptiometry (DXA) scan. |
Secondary
| Measure | Time frame |
|---|---|
| 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: 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: 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 |
| 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: 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 |
Countries
United States
Participant flow
Recruitment details
The study was planned to have 4 groups of patients. In Group 1: the bioavailability of BVS857 following subcutaneous administration was planned. Groups 2-4 (Group 4 optional) different BVS857 doses were planned for safety, PK and efficacy assessments. Study was terminated due to low enrollment as only 1 patient was enrolled
Participants by arm
| Arm | Count |
|---|---|
| BVS857 Grp 1A Open Label 0.03 mg/kg of BVS857 intravenously in open label manner followed by subsequent subcutaneous doses weekly at day 15,22 and 29. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | BVS857 Grp 1A Open Label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Efficacy Measure by Change in Lean Body Mass (LBM)
Total LBM is measured by dual energy X-ray absorptiometry (DXA) scan.
Time frame: Groups 2,3&4: Baseline, Day 35, Day 85 and Day 106
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Primary
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
Time frame: Over 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BVS857 Grp 1A Open Label | Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Death | 0 Participants |
| BVS857 Grp 1A Open Label | Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Adverse Events | 1 Participants |
| BVS857 Grp 1A Open Label | Number of Patients With Adverse Events as a Measure of Safety and Tolerability | Serious Adverse Events | 0 Participants |
Secondary
Serum Pharmacokinetics (PK) of BVS857: AUCinf; The Area Under the Plasma (or Serum or Blood) Concentration-time Curve From Time Zero to Infinity
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
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
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: CL/F; The Apparent Systemic (or Total Body) Clearance From Plasma (or Serum or Blood) Following Extravascular Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: CL; The Systemic (or Total Body) Clearance From Plasma (or Serum or Blood) Following Intravenous Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: Cmax; The Observed Maximum Plasma (or Serum or Blood) Concentration Following Drug Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: T1/2; The Terminal Elimination Half-life
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:ay D1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: Tmax; The Time to Reach the Maximum Concentration After Drug Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: Vss; The Volume of Distribution at Steady State Following Intravenous Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: Vz/F; The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided
Secondary
Serum Pharmacokinetics (PK) of BVS857: Vz; The Volume of Distribution During the Terminal Elimination Phase Following Intravenous Administration
Time frame: Groups 1: Day 1through to Day 56: Groups 2,3&4:Day 1 through to Day 105
Population: Terminated study underpowered due to low enrollment (n=1 patient). No analysis can be provided