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 and/or risdiplam and/or have a history of onasemnogene abeparvovec, 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

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 & 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 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

Name	Time	Method
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score	Baseline to Week 48	The RULM includes 20 items, graded from 0 to 2, with a maximum score of 37. Higher scores indicate better function.
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS)	Baseline to Week 48	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.
Change from Baseline in lean body mass	Baseline, Week 48	Body mass will be measured as change in kg (greater change meaning more improvement)
Change from Baseline in bone mineral density	Baseline, Week 48	Bone mineral density will be measured by Z-score change (higher score indicates improvement)
Change from baseline in Tanner staging	Baseline, Week 48
Injection acceptability assessments	Week 48	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
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

Trial Locations

Locations (53): Phoenix Children's
🇺🇸
Phoenix, Arizona, 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
UF Health, Shands Hospital
🇺🇸
Gainesville, Florida, United States
Rare Disease Research
🇺🇸
Atlanta, Georgia, United States
Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸
Chicago, Illinois, United States
Indiana University -Riley Research
🇺🇸
Indianapolis, Indiana, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
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Phoenix Children's
🇺🇸Phoenix, Arizona, United States