Spinal and Bulbar Muscular Atrophy
Conditions
Brief summary
The purpose of this study was to determine if BVS857 is safe, tolerable and increases thigh muscle thickness in patients with spinal bulbar and muscular atrophy (SBMA).
Interventions
DRUGBVS857
BVS857 lyophilisate in vial; the lyophilisate was reconstituted with sterile water for injection, diluted as appropriate, and administered either i.v. or s.c..
DRUGPlacebo
Placebo lyophilisate in vial; the lyophilisate was reconstituted with sterile water for injection, diluted as appropriate, and administered either i.v. or s.c..
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Genetic diagnosis of SBMA with symptomatic muscle weakness * Able to complete 2 minute timed walk * Serum IGF-1 level less than or equal to 170 ng/mL Key
Exclusion criteria
* Medically treated diabetes mellitus or known history of hypoglycemia * History of Bell's palsy * Treatment with systemic steroids \> 10 mg/day (or equivalent dose); androgens or androgen reducing agents; systemic beta agonists; or other muscle anabolic drugs within the previous 3 months * History of cancer, other than non-melanomatous skin cancer * Retinopathy * Papilledema Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | After 78 days in Part A and after 85 days in Part B. | Safety was monitored throughout the study. |
| Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | After 78 days in Part A and after 85 days in Part B. | Safety was monitored throughout the study. |
| Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5 | Baseline, Day 85 | Thigh muscle volume was assessed by magnetic resonance imaging (MRI). Change from baseline was calculated from the ratio of the post-baseline mean value to the baseline mean value: \[(Day 85/baseline) - 1)\] x 100. A positive change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Day 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4 | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5 | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5 | Baseline, Day 85 | The AMAT rated physical function and muscle endurance, with higher scores indicating better performance. The tool includes 7 timed functional tasks rated on a scale from 0 - 21 and 6 endurance tasks rated on a scale from 0 - 24. The range for the total score was from 0 (worst) to 45 (best). A positive change from baseline indicates improvement. |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5 | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5 | Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4 | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose | Serum samples were obtained for the PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5 | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | — |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2) | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations | In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. | Serum samples were obtained for PK assessment. |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4 | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose | Serum samples were obtained for PK assessment. |
| Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5 | Baseline, Day 85 | LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement. |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose | Serum samples were obtained for PK assessment. |
Countries
Denmark, Germany, Italy, United States
Participant flow
Recruitment details
This study was conducted in 2 parts, Part A and Part B. In Part A, Cohort 1 participants received open-label BVS857. Cohort 2 participants were randomized to double-blind BVS857 or double-blind placebo in a 2:1 ratio.
Pre-assignment details
In Part B, Cohort 3 was not enrolled. Cohort 4 participants received open-label BVS857. Cohort 5 participants were randomized to double-blind BVS857 or double-blind placebo in a ratio of 18:10.
Participants by arm
| Arm | Count |
|---|---|
| BVS857 Part A Open Label (Cohort 1) Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. | 2 |
| BVS857 Part A Double Blind (Cohort 2) Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) | 4 |
| Placebo Part A Double Blind (Cohort 2) Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. | 2 |
| BVS857 Part B Open-label (Cohort 4) Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. | 2 |
| BVS857 Part B Double Blind (Cohort 5) Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. | 18 |
| Placebo Part B Double Blind (Cohort 5) Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. | 9 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal laboratory value | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Adverse Event | 2 | 3 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | BVS857 Part A Open Label (Cohort 1) | BVS857 Part A Double Blind (Cohort 2) | Placebo Part A Double Blind (Cohort 2) | BVS857 Part B Open-label (Cohort 4) | BVS857 Part B Double Blind (Cohort 5) | Placebo Part B Double Blind (Cohort 5) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 67.0 Years STANDARD_DEVIATION 5.66 | 56.0 Years STANDARD_DEVIATION 12.33 | 59.5 Years STANDARD_DEVIATION 7.78 | 41.5 Years STANDARD_DEVIATION 4.95 | 57.0 Years STANDARD_DEVIATION 55.5 | 54.0 Years STANDARD_DEVIATION 5.94 | 56.0 Years STANDARD_DEVIATION 10.33 |
| Sex/Gender, Customized Male | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 18 Participants | 9 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 4 / 4 | 1 / 2 | 17 / 18 | 8 / 9 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 4 | 0 / 2 | 0 / 18 | 0 / 9 |
Outcome results
Primary
Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5
Thigh muscle volume was assessed by magnetic resonance imaging (MRI). Change from baseline was calculated from the ratio of the post-baseline mean value to the baseline mean value: \[(Day 85/baseline) - 1)\] x 100. A positive change from baseline indicates improvement.
Time frame: Baseline, Day 85
Population: The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5 | 0.0 Percent change | Standard Deviation 2.42 |
| BVS857 Part A Double Blind (Cohort 2) | Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5 | -3.4 Percent change | Standard Deviation 4.79 |
p-value: 0.016490% CI: [1.009, 1.065]ANCOVA
Primary
Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability
Safety was monitored throughout the study.
Time frame: After 78 days in Part A and after 85 days in Part B.
Population: The safety analysis set, which included participants who received any study drug, was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Moderate | 1 Participants |
| BVS857 Part A Open Label (Cohort 1) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Mild | 1 Participants |
| BVS857 Part A Open Label (Cohort 1) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Severe | 0 Participants |
| BVS857 Part A Double Blind (Cohort 2) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Moderate | 2 Participants |
| BVS857 Part A Double Blind (Cohort 2) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Mild | 2 Participants |
| BVS857 Part A Double Blind (Cohort 2) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Severe | 0 Participants |
| Placebo Part A Double Blind (Cohort 2) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Moderate | 0 Participants |
| Placebo Part A Double Blind (Cohort 2) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Severe | 0 Participants |
| Placebo Part A Double Blind (Cohort 2) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Mild | 2 Participants |
| BVS857 Part B Open-label (Cohort 4) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Moderate | 0 Participants |
| BVS857 Part B Open-label (Cohort 4) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Mild | 0 Participants |
| BVS857 Part B Open-label (Cohort 4) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Severe | 0 Participants |
| BVS857 Part B Double Blind (Cohort 5) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Moderate | 11 Participants |
| BVS857 Part B Double Blind (Cohort 5) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Mild | 5 Participants |
| BVS857 Part B Double Blind (Cohort 5) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Severe | 1 Participants |
| Placebo Part B Double Blind (Cohort 5) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Mild | 4 Participants |
| Placebo Part B Double Blind (Cohort 5) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Severe | 1 Participants |
| Placebo Part B Double Blind (Cohort 5) | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Moderate | 3 Participants |
Primary
Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability
Safety was monitored throughout the study.
Time frame: After 78 days in Part A and after 85 days in Part B.
Population: The safety analysis set, which included participants who received any study drug, was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | SAEs | 0 Participants |
| BVS857 Part A Open Label (Cohort 1) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Non-serious AEs | 2 Participants |
| BVS857 Part A Open Label (Cohort 1) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Deaths | 0 Participants |
| BVS857 Part A Double Blind (Cohort 2) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | SAEs | 0 Participants |
| BVS857 Part A Double Blind (Cohort 2) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Non-serious AEs | 4 Participants |
| BVS857 Part A Double Blind (Cohort 2) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Deaths | 0 Participants |
| Placebo Part A Double Blind (Cohort 2) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | SAEs | 0 Participants |
| Placebo Part A Double Blind (Cohort 2) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Non-serious AEs | 2 Participants |
| Placebo Part A Double Blind (Cohort 2) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Deaths | 0 Participants |
| BVS857 Part B Open-label (Cohort 4) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | SAEs | 0 Participants |
| BVS857 Part B Open-label (Cohort 4) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Non-serious AEs | 1 Participants |
| BVS857 Part B Open-label (Cohort 4) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Deaths | 0 Participants |
| BVS857 Part B Double Blind (Cohort 5) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | SAEs | 0 Participants |
| BVS857 Part B Double Blind (Cohort 5) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Non-serious AEs | 17 Participants |
| BVS857 Part B Double Blind (Cohort 5) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Deaths | 0 Participants |
| Placebo Part B Double Blind (Cohort 5) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Non-serious AEs | 8 Participants |
| Placebo Part B Double Blind (Cohort 5) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Deaths | 0 Participants |
| Placebo Part B Double Blind (Cohort 5) | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | SAEs | 0 Participants |
Secondary
Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations
Serum samples were obtained for PK assessment.
Time frame: In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose.
Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Secondary
Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5
The AMAT rated physical function and muscle endurance, with higher scores indicating better performance. The tool includes 7 timed functional tasks rated on a scale from 0 - 21 and 6 endurance tasks rated on a scale from 0 - 24. The range for the total score was from 0 (worst) to 45 (best). A positive change from baseline indicates improvement.
Time frame: Baseline, Day 85
Population: The PD set included, which included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data, was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5 | 1.0 score on a scale | Standard Deviation 4.2 |
| BVS857 Part A Double Blind (Cohort 2) | Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5 | 2.3 score on a scale | Standard Deviation 1.87 |
Secondary
Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5
LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement.
Time frame: Baseline, Day 85
Population: The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5 | 0.77 kilograms | Standard Deviation 1.556 |
| BVS857 Part A Double Blind (Cohort 2) | Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5 | 0.16 kilograms | Standard Deviation 1.199 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Day 1, 0.01 mg/kg BVS857 i.v. | 184 ng/mL | Standard Deviation 6.36 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Day 15, 0.01 mg/kg BVS857 s.c. | 34.6 ng/mL | Standard Deviation 48.9 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Day 29, 0.03 mg/kg BVS857 s.c | 83.1 ng/mL | Standard Deviation 20.3 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Day 43, 0.06 mg/kg BVS857 s.c. | 74.2 ng/mL | Standard Deviation 16.1 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Day 1, 0.03 mg/kg BVS857 i.v. (n=4) | 393 ng/mL | Standard Deviation 30.1 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Day 15, 0.03 mg/kg BVS857 s.c. (n=3) | 77.3 ng/mL | Standard Deviation 46.5 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Day 29, 0.06 mg/kg BVS857 s.c. (n=2) | 113 ng/mL | Standard Deviation 2.12 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Day 43, 0.10 mg/kg BVS857 s.c. (n=3) | 191 ng/mL | Standard Deviation 19.2 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Day 57, 0.10 mg/kg BVS857 s.c. (n=1) | 232 ng/mL | — |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4
Serum samples were obtained for PK assessment.
Time frame: Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
Population: The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4 | 2490 ng/mL | Standard Deviation 799 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5
Serum samples were obtained for PK assessment.
Time frame: Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5 | Day 1, 0.06 mg/kg BVS857 i.v. (n=18) | 854 ng/mL | Standard Deviation 669 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5 | Day 36, 0.06 mg/kg BVS857 i.v. (n=16) | 790 ng/mL | Standard Deviation 184 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5 | Day 78, 0.06 mg/kg BVS857 i.v. (n=16) | 712 ng/mL | Standard Deviation 218 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Day 1, 0.01 mg/kg BVS857 i.v.(n=2) | 4620 h*ng/mL | Standard Deviation 1200 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Day 15, 0.01 mg/kg BVS857 s.c. (n=1) | 2120 h*ng/mL | — |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Day 29, 0.03 mg/kg BVS857 s.c. (n=2) | 2720 h*ng/mL | Standard Deviation 870 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Day 43, 0.06 mg/kg BVS857 s.c. (n=2) | 2210 h*ng/mL | Standard Deviation 339 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Day 1, 0.03 mg/kg BVS857 i.v. (n=4) | 7980 h*ng/mL | Standard Deviation 1710 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Day 15, 0.03 mg/kg BVS857 s.c. (n=3) | 2640 h*ng/mL | Standard Deviation 1500 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Day 29, 0.06 mg/kg BVS857 s.c. (n=2) | 3880 h*ng/mL | Standard Deviation 735 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Day 43, 0.10 mg/kg BVS857 s.c. (n=3) | 6390 h*ng/mL | Standard Deviation 925 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Day 57, 0.10 mg/kg BVS857 s.c. (n=1) | 7360 h*ng/mL | — |
Secondary
Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4
Serum samples were obtained for the PK assessment.
Time frame: Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
Population: The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4 | 40600 H*ng/mL | Standard Deviation 1270 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5
Time frame: Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5 | Day 1, 0.06 mg/kg BVS857 i.v. (n=18) | 19400 h*ng/mL | Standard Deviation 4160 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5 | Day 36, 0.06 mg/kg BVS857 i.v.(n=16) | 19600 h*ng/mL | Standard Deviation 5240 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5 | Day 78, 0.06 mg/kg BVS857 i.v. (n=16) | 18100 h*ng/mL | Standard Deviation 5850 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf)
Serum samples were obtained for PK assessment.
Time frame: Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau)
Serum samples were obtained for PK assessment.
Time frame: Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Day 1, 0.01 mg/kg BVS857 i.v.(n=2) | 4630 h*ng/mL | Standard Deviation 1200 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Day 15, 0.01 mg/kg BVS857 s.c. (n=2) | 1060 h*ng/mL | Standard Deviation 1500 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Day 29, 0.03 mg/kg BVS857 s.c.(n=2) | 2720 h*ng/mL | Standard Deviation 870 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Day 43, 0.06 mg/kg BVS857 s.c.(n=2) | 5310 h*ng/mL | Standard Deviation 4720 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Day 1, 0.03 mg/kg BVS857 i.v.(n=4) | 9850 H*ng/mL | Standard Deviation 4480 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Day 15, 0.03 mg/kg BVS857 s.c. (n=3) | 6480 H*ng/mL | Standard Deviation 5850 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Day 29, 0.06 mg/kg BVS857 s.c. (n=2) | 7340 H*ng/mL | Standard Deviation 5610 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Day 43, 0.10 mg/kg BVS857 s.c. (n=3) | 14400 H*ng/mL | Standard Deviation 3320 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Day 57, 0.10 mg/kg BVS857 s.c. (n=1) | 28400 H*ng/mL | — |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5
Serum samples were obtained for PK assessment.
Time frame: Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5 | Day 36, 0.06 mg/kg BVS857 i.v. (n=1) | 13100 h*ng/mL | — |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5 | Day 78, 0.06 mg/kg BVS857 i.v. (n=15) | 28000 h*ng/mL | Standard Deviation 13500 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2)
Serum samples were obtained for PK assessment.
Time frame: Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated.
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1
Serum samples were obtained for PK assessment.
Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Day 1, 0.01 mg/kg BVS857 i.v. (n=2) | 4.04 hours | Standard Deviation 0.0566 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Day 15, 0.01 mg/kg BVS857 s.c. (n=1) | 12.1 hours | — |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Day 29, 0.03 mg/kg BVS857 s.c.(n=2) | 18.1 hours | Standard Deviation 8.41 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Day 43, 0.06 mg/kg BVS857 s.c. (n=2) | 36.0 hours | Standard Deviation 16.8 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2
Serum samples were obtained for PK assessment.
Time frame: Day 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Day 1, 0.03 mg/kg BVS857 i.v. (n=4) | 2.53 hours | Standard Deviation 1.7 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Day 15, 0.03 mg/kg BVS857 s.c.(n=3) | 24.1 hours | Standard Deviation 0.1 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Day 29, 0.06 mg/kg BVS857 s.c. (n=2) | 24.0 hours | Standard Deviation 0 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Day 43, 0.10 mg/kg BVS857 s.c. (n=3) | 24.0 hours | Standard Deviation 0.2 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Day 57, 0.10 mg/kg BVS857 s.c. (n=1) | 48.0 hours | — |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4
Serum samples were obtained for PK assessment.
Time frame: Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
Population: The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4 | 1.08 hours | Standard Deviation 0.0707 |
Secondary
Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5
Serum samples were obtained for PK assessment.
Time frame: Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
Population: For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5 | Day 1, 0.06 mg/kg BVS857 i.v. (n=18) | 2.39 hours | Standard Deviation 1.54 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5 | Day 36, 0.06 mg/kg BVS857 i.v. (n=16) | 1.73 hours | Standard Deviation 1.2 |
| BVS857 Part A Open Label (Cohort 1) | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5 | Day 78, 0.06 mg/kg BVS857 i.v. (n=16) | 1.49 hours | Standard Deviation 1.04 |