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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified December 2025 by Biohaven Pharmaceuticals, Inc.
Sponsor
Biohaven Pharmaceuticals, Inc.
Information Provided by (Responsible Party)
Biohaven Pharmaceuticals, Inc.
Clinicaltrials.gov Identifier
NCT05337553
Other Study ID Numbers:
BHV2000-301
First Submitted
April 13, 2022
First Posted
April 19, 2022
Last Update Posted
February 3, 2026
Last Verified
December 2025

ClinicalTrials.gov processed this data on January 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Spinal Muscular AtrophyNeuromuscular DiseasesSMA
Drug: taldefgrobep alfaDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment269 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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
Study Start DateJuly 5, 2022
Actual Primary Completion DateSeptember 24, 2024
Actual Study Completion Date2w 2d from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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
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

Outcome Measures

Primary Outcome Measures
  1. 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.
Secondary Outcome Measures
  1. 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.
  2. 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.
  3. Change from Baseline in lean body mass
    Body mass will be measured as change in kg (greater change meaning more improvement)
  4. Change from Baseline in bone mineral density
    Bone mineral density will be measured by Z-score change (higher score indicates improvement)
  5. Change from baseline in Tanner staging
  6. 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
  7. 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
  8. Trough plasma concentration

Eligibility Criteria

Ages Eligible for Study(Child, Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

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