A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
- Conditions
- SMANeuromuscular DiseasesSpinal Muscular Atrophy
- Interventions
- Drug: Placebo
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 269
- 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
- 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 & 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.
- Secondary Outcome Measures
Name Time Method
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