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

NCT02024932 | Completed Phase 2 Results DMC

• 1 other identifier: CBVS857X2202
• Study Type: interventional
• Target: 37
• Locations: 4 countries
• Sites: 6

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).

Conditions

Spinal and Bulbar Muscular Atrophy

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (21)

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

  Baseline, Day 85

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

  Baseline, Day 85

• 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

• 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

• 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

Study Arms (6)

BVS857 Part A Open label (Cohort 1)

EXPERIMENTAL

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.

Drug: BVS857

BVS857 Part A double blind (Cohort 2)

EXPERIMENTAL

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.)

Drug: BVS857

Placebo Part A double blind (Cohort 2)

PLACEBO COMPARATOR

Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57.

Drug: Placebo

BVS857 Part B open-label (Cohort 4)

EXPERIMENTAL

Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks.

Drug: BVS857

BVS857 Part B double blind (Cohort 5)

EXPERIMENTAL

Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks.

Drug: BVS857

Placebo Part B double blind (Cohort 5)

PLACEBO COMPARATOR

Participants received matching placebo i.v. to BVS857 weekly for 12 weeks.

Drug: Placebo

Interventions

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..

BVS857 Part A Open label (Cohort 1); BVS857 Part A double blind (Cohort 2); BVS857 Part B double blind (Cohort 5); BVS857 Part B open-label (Cohort 4)

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..

Placebo Part A double blind (Cohort 2); Placebo Part B double blind (Cohort 5)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Orange, California, 92868, United States

Location

National Institutes of Health

Bethesda, Maryland, 20892, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43210, United States

Location

Novartis Investigative Site

Copenhagen, 2100, Denmark

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Related Publications (1)

• Grunseich C, Miller R, Swan T, Glass DJ, El Mouelhi M, Fornaro M, Petricoul O, Vostiar I, Roubenoff R, Meriggioli MN, Kokkinis A, Guber RD, Budron MS, Vissing J, Soraru G, Mozaffar T, Ludolph A, Kissel JT, Fischbeck KH; BVS857 study group. Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial. Lancet Neurol. 2018 Dec;17(12):1043-1052. doi: 10.1016/S1474-4422(18)30320-X. Epub 2018 Oct 15.

  PMID: 30337273 DERIVED

Related Links

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

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-1873

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2013
• First Posted: December 31, 2013
• Study Start: February 4, 2014
• Primary Completion: April 13, 2016
• Study Completion: April 13, 2016
• Last Updated: January 5, 2021
• Results First Posted: August 11, 2017

Record last verified: 2019-03

Locations

DE (1); DK (1); US (3); IT (1)