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

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

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 and/or risdiplam and/or have a history of onasemnogene abeparvovec, compared to placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuromuscular Diseases; Spinal Muscular Atrophy; SMA
• Intervention / Treatment: Drug: Placebo; Drug: taldefgrobep alfa; Drug: taldefgrobep alfa

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
• Enrollment (Actual): 269
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 02650
    • University Hospital Antwerp
  • Ghent, Belgium, 09000
    • University Hospital Ghent
  • Leuven, Belgium, 03000
    • University Hospital Leuven
• Czechia
  • Brno, Czechia, 625 00
    • University Hospital Brno - Dept. of Pediatric Neurology
  • Prague, Czechia, 150 06
    • Motol University Hospital
• Germany
  • Essen, Germany, 45147
    • University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I
  • Freiburg im Breisgau, Germany, 79106
    • University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders
  • Munich, Germany, 80337
    • Dr. Von Haunersches Children'S Hospital - Lmu Munich
• Italy
  • Bologna, Italy, 40139
    • Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital
  • Gussago, Italy, 25064
    • Nemo-Brescia Clinical Center For Neuromuscular Diseases
  • Pavia, Italy, 27100
    • IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT
  • Roma, Italy, 00165
    • Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• Poland
  • Gdansk, Poland, 80-925
    • University Clinical Centre in Gdansk - Dept. of Developmental Neurology
  • Poznan, Poland, 60-355
    • Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic
  • Warsaw, Poland, 04-730
    • The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology
  • Wroclaw, Poland, 54-049
    • T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.
• Spain
  • Donostia / San Sebastian, Spain, 20014
    • Donostia University Hospital
  • Esplugues de Llobregat, Spain, 08950
    • Hospital Sant Joan de Déu
  • Málaga, Spain, 29011
    • Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit
  • Valencia, Spain, 46026
    • La Fe University and Polytechnic Hospital
• United Kingdom
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Royal Hospital for Children
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's
  • California
    • La Jolla, California, United States, 92037
      • UCSD & Rady Children's
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • San Francisco, California, United States, 94158
      • UCSF Benioff Children's Hospital, Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health, Shands Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Rare Disease Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University -Riley Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital - Harvard
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • BSHS Office of Research
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • CHOP Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78723
      • UT Pediatric Neurosciences/Dell Children's Medical Center
    • Denton, Texas, United States, 75208
      • Neurology Rare Disease Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Children's Hospital
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute of Research and Innovation
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 and/or 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Open label Extension (OLE) phase.	Drug: taldefgrobep alfa; DB Phase: 35 mg/50 mg weekly subcutaneous injection; Other Names: BHV-2000; BMS-986089; Drug: taldefgrobep alfa; Extension Phase: 35 mg/50 mg weekly subcutaneous injection; Other Names: BHV-2000; BMS-986089
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 OLE phase.	Drug: Placebo; DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection; Drug: taldefgrobep alfa; DB Phase: 35 mg/50 mg weekly subcutaneous injection; Other Names: BHV-2000; BMS-986089; Drug: taldefgrobep alfa; Extension Phase: 35 mg/50 mg weekly subcutaneous injection; Other Names: BHV-2000; BMS-986089

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score	Change in MFM-32 total score from baseline to Week 48. Scores range from 0-3 on each item. The scores from the 32 items are summed and transformed to a 0-100 scale, with higher scores reflecting higher levels of functional abilities.	Baseline to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score	The RULM includes 20 items, graded from 0 to 2, with a maximum score of 37. Higher scores indicate better function.	Baseline to Week 48
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS)	The RHS has a maximum score of 69 points (33 items are scored 0-2, and 3 items scored 0-1). Higher scores indicate better function.	Baseline to Week 48
Change from Baseline in lean body mass	Body mass will be measured as change in kg (greater change meaning more improvement)	Baseline, Week 48
Change from Baseline in bone mineral density	Bone mineral density will be measured by Z-score change (higher score indicates improvement)	Baseline, Week 48
Change from baseline in Tanner staging		Baseline, Week 48
Injection acceptability assessments	If local injection site reactions (such as redness, itching, swelling, hardening or bruising) are experienced, the acceptability is scored on a scale of 1-5 with 1 being totally acceptable and 5 being not at all acceptable If pain is experienced at the injection site, pain will be scored on a scale of 1-5 with 1 being totally acceptable and 5 being not at all acceptable	Week 48
Number of Participants with new or worsening lab abnormalities, Adverse Events (AEs), Serious AEs (SAEs) and AEs Leading to Study Drug Discontinuation in the Double-blind Phase		Up to 48 Weeks
Trough plasma concentration		Baseline, Week 12, Week 24, Week 36, Week 48

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2022
• Primary Completion (Actual): September 25, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Neuromuscular Diseases; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: BHV2000-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No