Safety, Tolerability, and Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy

Spinal and Bulbar Muscular Atrophy Clinical Trial

Official title:

A Two-part Placebo-controlled Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy (SBMA)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02024932
• Other study ID #: CBVS857X2202
• Status: Completed
• Phase: Phase 2
• Start date: February 4, 2014
• Est. completion date: April 13, 2016

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: April 13, 2016
• Est. primary completion date: April 13, 2016
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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/exclusion criteria may apply

Related Conditions & MeSH terms

• Atrophy
• Bulbo-Spinal Atrophy, X-Linked
• Muscular Atrophy
• Spinal and Bulbar Muscular Atrophy

Intervention

Drug:
• BVS857
BVS857 lyophilisate in vial; the lyophilisate was reconstituted with sterile water for injection, diluted as appropriate, and administered either i.v. or s.c..
• Placebo
Placebo lyophilisate in vial; the lyophilisate was reconstituted with sterile water for injection, diluted as appropriate, and administered either i.v. or s.c..

Locations

Country	Name	City	State
Denmark	Novartis Investigative Site	Copenhagen
Germany	Novartis Investigative Site	Ulm
Italy	Novartis Investigative Site	Padova	PD
United States	National Institutes of Health	Bethesda	Maryland
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Denmark,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	After 78 days in Part A and after 85 days in Part B.
Primary	Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability	Safety was monitored throughout the study.	After 78 days in Part A and after 85 days in Part B.
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.	Baseline, Day 85
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.	Baseline, Day 85
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.	Baseline, Day 85
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.	Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
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.	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
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.	Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
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.	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
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.	Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
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.	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
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.	Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose
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.	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
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.	Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
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.	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.
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.	Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
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.	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.
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.	Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose.
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.	Days 1: pre-dose, 1, 4, 24, 48 hours post-dose
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		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.
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.	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.
Secondary	Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2)	Serum samples were obtained for PK assessment.	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.
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.	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.
Secondary	Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations	Serum samples were obtained for PK assessment.	In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose.

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com