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

Brief Summary

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)”

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).

  • 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
  • Study Primary Completion Date: October 2015

Interventions Used in this Clinical Trial

  • Drug: BVS857
    • BVS857 i.v. and escalating s.c. doses
  • Drug: Placebo
    • Placebo i.v. and s.c. doses
  • Drug: BVS857
    • BVS857 s.c. doses
  • Drug: Placebo
    • Placebo s.c. doses

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: BVS857 Part A Open label
  • Experimental: BVS857 Part A double blind
  • Placebo Comparator: Placebo Part A double blind
  • Experimental: BVS857 Part B double blind
  • Placebo Comparator: Placebo Part B double blind

Outcome Measures for this Clinical Trial

Primary 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.
      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.
      Safety Issue?: Yes
  • Change in thigh muscle volume
    • Time Frame: Baseline and Day 85 in Part B.
      Safety Issue?: No

Secondary Measures

  • Change in score on the adult myopathy assessment tool.
    • Time Frame: Baseline and Day 85 in Part B.
      Safety Issue?: No
  • Change in lean body mass.
    • Time Frame: Baseline and Day 85 in Part B.
      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. On day 57, pre-dose. 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36, pre-dose, 4, 24, 48 hours post-dose. On day 78, pre-dose, 4, 24, 48, 168 hours post-dose.
      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. On day 57, pre-dose. 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36, pre-dose, 4, 24, 48 hours post-dose. On day 78, pre-dose, 4, 24, 48, 168 hours post-dose.
      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. On day 57, pre-dose. 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36, pre-dose, 4, 24, 48 hours post-dose. On day 78, pre-dose, 4, 24, 48, 168 hours post-dose.
      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. On day 57, pre-dose. 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36, pre-dose, 4, 24, 48 hours post-dose. On day 78, pre-dose, 4, 24, 48, 168 hours post-dose.
      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. On day 57, pre-dose. 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36, pre-dose, 4, 24, 48 hours post-dose. On day 78, pre-dose, 4, 24, 48, 168 hours post-dose.
      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. On day 57, pre-dose. 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36, pre-dose, 4, 24, 48 hours post-dose. On day 78, pre-dose, 4, 24, 48, 168 hours post-dose.
      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.
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals
  • Overall Contact(s)
    • Novartis Pharmaceuticals, 1-888-669-6682

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT02024932