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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02024932
First received: December 29, 2013
Last updated: July 12, 2016
Last verified: July 2016
  Purpose
The purpose of this study is to determine if BVS857 is safe, tolerable and increases thigh muscle thickness in patients with spinal bulbar and muscular atrophy (SBMA).

Condition Intervention Phase
Spinal and Bulbar Muscular Atrophy
Drug: BVS857
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: After 78 days in Part A and after 85 days in Part B. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • Change in thigh muscle volume [ Time Frame: Baseline and Day 85 in Part B. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in score on the adult myopathy assessment tool. [ Time Frame: Baseline and Day 85 in Part B. ] [ Designated as safety issue: No ]
  • Change in lean body mass. [ Time Frame: Baseline and Day 85 in Part B. ] [ Designated as safety issue: No ]
  • Plasma Pharmacokinetics (PK) of BVS857: Observed maximum concentration following drug administration (Cmax) [ 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. ] [ Designated as safety issue: No ]
  • Plasma Pharmacokinetics (PK) of BVS857: Time to reach the maximum concentration after drug administration (Tmax) [ 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. ] [ Designated as safety issue: No ]
  • 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) [ 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: February 2014
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BVS857 Part A Open label Drug: BVS857
BVS857 i.v. and escalating s.c. doses
Experimental: BVS857 Part A double blind Drug: BVS857
BVS857 i.v. and escalating s.c. doses
Placebo Comparator: Placebo Part A double blind Drug: Placebo
Placebo i.v. and s.c. doses
Experimental: BVS857 Part B double blind Drug: BVS857
BVS857 i.v. doses
Placebo Comparator: Placebo Part B double blind Drug: Placebo
Placebo i.v. doses

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02024932

Locations
United States, California
Novartis Investigative Site
Orange, California, United States, 92868
United States, Maryland
National Institutes of Health
Bethesda, Maryland, United States, 20892
United States, Ohio
Novartis Investigative Site
Columbus, Ohio, United States, 43210
Denmark
Novartis Investigative Site
Copenhagen, Denmark, 2100
Germany
Novartis Investigative Site
Ulm, Germany, 89081
Italy
Novartis Investigative Site
Padova, PD, Italy, 35128
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02024932     History of Changes
Other Study ID Numbers: CBVS857X2202 
Study First Received: December 29, 2013
Last Updated: July 12, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy
Muscular Disorders, Atrophic
Bulbo-Spinal Atrophy, X-Linked
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Muscular Atrophy, Spinal
Spinal Cord Diseases
Central Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Motor Neuron Disease
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 21, 2016