A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (RESILIENT)

• ClinicalTrials.gov Identifier: NCT05337553
• Recruitment Status: Active, not recruiting
• First Posted: April 20, 2022
• Last Update Posted: November 7, 2023
• Sponsor: Biohaven Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Biohaven Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: April 14, 2022
• First Posted Date: April 20, 2022
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: July 6, 2022
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 14, 2022)

Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score [ Time Frame: Baseline to Week 48 ]

Change in MFM-32 total score from baseline to Week 48. Scores range from 0-3 on each item. The higher the score, indicates higher functioning.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Ambulatory and Non-Ambulatory Participants With Spinal Muscular Atrophy With Open-Label Extension
• Brief Summary: This trial will study the efficacy and safety of taldefgrobep alfa as an adjunctive therapy for participants who are already taking a stable dose of nusinersen or risdiplam or have a history of onasemnogene abeparvovec-xioi, compared to placebo.
• Detailed Description: Myostatin is a negative regulator of muscle growth. Blocking myostatin activity has been shown to increase muscle size and function. Taldefgrobep alfa directly blocks myostatin activity and was well tolerated in other clinical studies. In combination with medications that increase the amount of SMN protein in the body, taldefgrobep alfa has the potential to further improve motor function and clinical measures for people living with SMA.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Spinal Muscular Atrophy
• Neuromuscular Diseases
• SMA

Intervention

• Drug: taldefgrobep alfa
  DB Phase: 35 mg/50 mg weekly subcutaneous injection
  Other Names:

  • BHV-2000
  • BMS-986089
• Drug: Placebo
  DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
• Drug: taldefgrobep alfa
  Extension Phase: 35 mg/50 mg weekly subcutaneous injection
  Other Names:

  • BHV-2000
  • BMS-986089

Study Arms

• Experimental: taldefgrobep alfa

  taldefgrobep alfa - Double-blind (DB) Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week DB phase.

  taldefgrobep alfa/taldefgrobep alfa - Extension Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week Open label Extension (OLE) phase.

  Interventions:

  • Drug: taldefgrobep alfa
  • Drug: taldefgrobep alfa
• Placebo Comparator: Placebo

  Placebo - Double-blind (DB) Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week DB phase.

  Placebo/taldefgrobep alfa - Extension Phase: Participants who receive placebo during DB phase, receive weight based 35 mg/50 mg weekly subcutaneous taldefgrobep alfa injection for 48-week OLE phase.

  Interventions:

  • Drug: Placebo
  • Drug: taldefgrobep alfa

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 4, 2023): 269
• Original Estimated Enrollment (submitted: April 14, 2022): 225
• Estimated Study Completion Date: January 2025
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Spinal Muscular Atrophy confirmed by genetic diagnosis of 5q-autosomal recessive SMA as well as SMN2 copy number
• Ambulant or Non-Ambulant
• Treated with an SMA disease-modifying therapy and anticipated to remain on that same treatment regimen and dose throughout the trial including nusinersen, risdiplam, and/or a history of onasemnogene abeparvovec

Key Exclusion Criteria:

• Cannot have previously taken anti-myostatin therapies
• Must weigh at least 15kg
• Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for daytime treatment while awake (use overnight or during daytime naps is acceptable)
• History of Spinal Fusion within 6 months of Screening. MAGEC rod nonsurgical adjustments are allowed during the study
• Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT05337553
• Other Study ID Numbers: BHV2000-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Biohaven Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Biohaven Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Lindsey Lair, MD; Biohaven Pharmaceuticals, Inc.

• PRS Account: Biohaven Pharmaceuticals, Inc.
• Verification Date: November 2023