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

NCT05337553 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: BHV2000-301
• Study Type: interventional
• Target: 269
• Locations: 9 countries
• Sites: 53

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

Conditions

Spinal Muscular Atrophy; Neuromuscular Diseases; SMA

Outcome Measures

Primary Outcomes (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.

  Baseline to Week 48

Secondary Outcomes (8)

• Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score

  Baseline to Week 48

• Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS)

  Baseline to Week 48

• Change from Baseline in lean body mass

  Baseline, Week 48

• Change from Baseline in bone mineral density

  Baseline, Week 48

• Change from baseline in Tanner staging

  Baseline, Week 48

Study Arms (2)

taldefgrobep alfa

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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; Drug: taldefgrobep alfa

Interventions

Placebo DRUG

DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection

Placebo

taldefgrobep alfa DRUG

DB Phase: 35 mg/50 mg weekly subcutaneous injection

Also known as: BHV-2000, BMS-986089

taldefgrobep alfa

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biohaven Pharmaceuticals, Inc.: lead

Study Sites (53)

Phoenix Children's

Phoenix, Arizona, 85016, United States

Location

UCSD & Rady Children's

La Jolla, California, 92037, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

UCSF Benioff Children's Hospital, Medical Center

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

UF Health, Shands Hospital

Gainesville, Florida, 32610, United States

Location

Rare Disease Research

Atlanta, Georgia, 30329, United States

Location

Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Indiana University -Riley Research

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Boston Children's Hospital - Harvard

Boston, Massachusetts, 02115, United States

Location

BSHS Office of Research

Grand Rapids, Michigan, 49503, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Duke University Medicine

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

CHOP Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Pediatric Neurosciences/Dell Children's Medical Center

Austin, Texas, 78723, United States

Location

Neurology Rare Disease Center

Denton, Texas, 75208, United States

Location

Cook Children's Hospital

Fort Worth, Texas, 76104, United States

Location

University of Virginia Children's Hospital

Charlottesville, Virginia, 22903, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

MultiCare Institute of Research and Innovation

Tacoma, Washington, 98405, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University Hospital Antwerp

Edegem, 02650, Belgium

Location

University Hospital Ghent

Ghent, 09000, Belgium

Location

University Hospital Leuven

Leuven, 03000, Belgium

Location

University Hospital Brno - Dept. of Pediatric Neurology

Brno, 625 00, Czechia

Location

Motol University Hospital

Prague, 150 06, Czechia

Location

University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I

Essen, 45147, Germany

Location

University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders

Freiburg im Breisgau, 79106, Germany

Location

Dr. Von Haunersches Children'S Hospital - Lmu Munich

Munich, 80337, Germany

Location

Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital

Bologna, 40139, Italy

Location

Nemo-Brescia Clinical Center For Neuromuscular Diseases

Gussago, 25064, Italy

Location

IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT

Pavia, 27100, Italy

Location

Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience

Roma, 00165, Italy

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

University Clinical Centre in Gdansk - Dept. of Developmental Neurology

Gdansk, 80-925, Poland

Location

Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic

Poznan, 60-355, Poland

Location

The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology

Warsaw, 04-730, Poland

Location

T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.

Wroclaw, 54-049, Poland

Location

Donostia University Hospital

Donostia / San Sebastian, 20014, Spain

Location

Hospital Sant Joan de Déu

Esplugues de Llobregat, 08950, Spain

Location

Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit

Málaga, 29011, Spain

Location

La Fe University and Polytechnic Hospital

Valencia, 46026, Spain

Location

Royal Hospital For Children

Glasgow, Scotland, G51 4TF, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Neuromuscular Diseases

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases

Study Officials

• Lindsey Lair, MD

  Biohaven Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 20, 2022
• Study Start: July 6, 2022
• Primary Completion: September 25, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); NL (1); GB (2); ES (4); BE (3); CZ (2); DE (3); PL (4); US (30)