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

Phase 3

Active, not recruiting

• Conditions: SMA; Neuromuscular Diseases; Spinal Muscular Atrophy
• Interventions: Drug: Placebo; Drug: taldefgrobep alfa

• Registration Number: NCT05337553
• Lead Sponsor: Biohaven Pharmaceuticals, Inc.

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 Timeline

• Study First Submitted: 2022-04-14
• Study First Submitted QC: 2022-04-14
• Study First Posted: 2022-04-20
• Study Start: 2022-07-06
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-06
• Last Update Posted: 2023-11-07
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 269

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
taldefgrobep alfa	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.
Placebo	taldefgrobep alfa	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.

Primary Outcome Measures

Name	Time	Method
Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score	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.

Trial Locations

Locations (53)

CHOP Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Motol University Hospital; 🇨🇿 Prague, Czechia

Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit; 🇪🇸 Málaga, Spain

Boston Children's Hospital - Harvard; 🇺🇸 Boston, Massachusetts, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

University Hospital Leuven; 🇧🇪 Leuven, Belgium

The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology; 🇵🇱 Warsaw, Poland

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.; 🇵🇱 Wrocław, Poland

BSHS Office of Research; 🇺🇸 Grand Rapids, Michigan, United States

Royal Hospital For Children; 🇬🇧 Glasgow, Scotland, United Kingdom

Phoenix Children's; 🇺🇸 Phoenix, Arizona, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital; 🇮🇹 Bologna, Italy

Penn State College of Medicine; 🇺🇸 Hershey, Pennsylvania, United States

Neurology Rare Disease Center; 🇺🇸 Denton, Texas, United States

University Hospital Ghent; 🇧🇪 Ghent, Belgium

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

UCSD & Rady Children's; 🇺🇸 La Jolla, California, United States

Children's Hospital of Los Angeles; 🇺🇸 Los Angeles, California, United States

UCSF Benioff Children's Hospital, Medical Center; 🇺🇸 San Francisco, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Rare Disease Research; 🇺🇸 Atlanta, Georgia, United States

UF Health, Shands Hospital; 🇺🇸 Gainesville, Florida, United States

Indiana University -Riley Research; 🇺🇸 Indianapolis, Indiana, United States

Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Washington University in St. Louis; 🇺🇸 Saint Louis, Missouri, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Stony Brook University Hospital; 🇺🇸 Stony Brook, New York, United States

Duke University Medicine; 🇺🇸 Durham, North Carolina, United States

UPMC Children's Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Cook Children's Hospital; 🇺🇸 Fort Worth, Texas, United States

University of Virginia Children's Hospital; 🇺🇸 Charlottesville, Virginia, United States

UT Pediatric Neurosciences/Dell Children's Medical Center; 🇺🇸 Austin, Texas, United States

Children's Hospital of The King's Daughters; 🇺🇸 Norfolk, Virginia, United States

MultiCare Institute of Research and Innovation; 🇺🇸 Tacoma, Washington, United States

University Hospital Antwerp; 🇧🇪 Edegem, Belgium

University Hospital Brno - Dept. of Pediatric Neurology; 🇨🇿 Brno, Czechia

University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I; 🇩🇪 Essen, Germany

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

Dr. Von Haunersches Children'S Hospital - Lmu Munich; 🇩🇪 Munich, Germany

Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience; 🇮🇹 Roma, Italy

Nemo-Brescia Clinical Center For Neuromuscular Diseases; 🇮🇹 Gussago, Italy

University Clinical Centre in Gdansk - Dept. of Developmental Neurology; 🇵🇱 Gdańsk, Poland

IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT; 🇮🇹 Pavia, Italy

Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic; 🇵🇱 Poznań, Poland

John Radcliffe Hospital; 🇬🇧 Oxford, United Kingdom

Donostia University Hospital; 🇪🇸 Donostia, Spain

La Fe University and Polytechnic Hospital; 🇪🇸 Valencia, Spain

Hospital Sant Joan de Déu; 🇪🇸 Esplugues De Llobregat, Spain

University of Kansas Medical Center; 🇺🇸 Fairway, Kansas, United States

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands