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

Biohaven

Status and phase: Active, not recruiting; Phase 3

Conditions: Neuromuscular Diseases; SMA; Spinal Muscular Atrophy

Treatments: Drug: Placebo; Drug: taldefgrobep alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT05337553

BHV2000-301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 269 patients

Sex: All

Ages: 4 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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269 participants in 2 patient groups, including a placebo group

taldefgrobep alfa

Experimental group

Description:

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.

Treatment:

Drug: taldefgrobep alfa

Drug: taldefgrobep alfa

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: taldefgrobep alfa

Drug: taldefgrobep alfa