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Completed

NCT Number: NCT02024932

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

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).

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Key information

Conditions

Spinal and Bulbar Muscular Atrophy Bulbo-Spinal Atrophy, X-Linked Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System Motor Neuron Disease Muscular Atrophy, Spinal Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Spinal Cord Diseases

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Copenhagen, Denmark

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BVS857

Drug

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

Drug

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

Primary outcomes

  1. Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability

    Time frame: After 78 days in Part A and after 85 days in Part B.

    Safety was monitored throughout the study.

  2. Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability

    Time frame: After 78 days in Part A and after 85 days in Part B.

    Safety was monitored throughout the study.

  3. Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5

    Time frame: 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 outcomes

  1. Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5

    Time frame: 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.

  2. Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5

    Time frame: Baseline, Day 85

    LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement.

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

    Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose

    Serum samples were obtained for PK assessment.

  4. Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2

    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

    Serum samples were obtained for PK assessment.

  5. Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1

    Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose

    Serum samples were obtained for PK assessment.

  6. Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2

    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

    Serum samples were obtained for PK assessment.

  7. 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

    Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose

    Serum samples were obtained for PK assessment.

  8. 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

    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

    Serum samples were obtained for PK assessment.

  9. 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

    Time frame: Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose

    Serum samples were obtained for PK assessment.

  10. 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

    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

    Serum samples were obtained for PK assessment.

  11. Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4

    Time frame: Days 1: pre-dose, 1, 4, 24, 48 hours post-dose

    Serum samples were obtained for PK assessment.

  12. Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) 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.

    Serum samples were obtained for PK assessment.

  13. Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4

    Time frame: Days 1: pre-dose, 1, 4, 24, 48 hours post-dose

    Serum samples were obtained for PK assessment.

  14. Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) 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.

    Serum samples were obtained for PK assessment.

  15. 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

    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.

    Serum samples were obtained for PK assessment.

  16. 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

    Time frame: Days 1: pre-dose, 1, 4, 24, 48 hours post-dose

    Serum samples were obtained for the PK assessment.

  17. 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.

  18. 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)

    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.

    Serum samples were obtained for PK assessment.

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

    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.

    Serum samples were obtained for PK assessment.

  20. Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf)

    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.

    Serum samples were obtained for PK assessment.

  21. Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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)

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Dec 31, 2013
Registry last updated
Jan 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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