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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A 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

Conditions
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SMA, Spinal Muscular Atrophy, Neuromuscular Diseases

Intervention / Treatment
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* Drug: taldefgrobep alfa
* Drug: Placebo
* Drug: taldefgrobep alfa


Participation Criteria
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Eligibility Criteria
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Key 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 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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: taldefgrobep alfa<br>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. | Drug: taldefgrobep alfa<br>* DB Phase: 35 mg/50 mg weekly subcutaneous injection<br>* Other names: BMS-986089;Drug: taldefgrobep alfa<br>* Extension Phase: 35 mg/50 mg weekly subcutaneous injection<br>* Other names: BMS-986089;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection<br>Drug: taldefgrobep alfa<br>* Extension Phase: 35 mg/50 mg weekly subcutaneous injection<br>* Other names: BMS-986089;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 higher the score, indicates higher functioning. | Baseline to Week 48 |