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

Phase 2CompletedNCT02024932

Novartis Pharmaceuticals37 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Spinal and Bulbar Muscular Atrophy

Interventions

BVS857DRUG

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

PlaceboDRUG

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

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (6)

Novartis Investigative Site

Orange, California, United States

National Institutes of Health

Bethesda, Maryland, United States

Novartis Investigative Site

Columbus, Ohio, United States

Novartis Investigative Site

Copenhagen, Denmark

Outcomes

Primary Outcomes

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.

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.

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

Secondary Outcomes

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

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

Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1

Data from ClinicalTrials.gov

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Novartis Investigative Site

Ulm, Germany

Novartis Investigative Site

Padua, PD, Italy

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

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

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

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

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

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

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

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

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

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.

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

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.

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.

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

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.

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.

Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2)

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)

Serum samples were obtained for PK assessment.

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.