A Study to Evaluate How Apitegromab Works in Subjects Who Are Less Than 2 Years Old and Have Spinal Muscular Atrophy

Not Applicable

Not yet recruiting

• Conditions: Neuromuscular Manifestations; Spinal Muscular Atrophy; Anti-myostatin; Spinal Muscular Atrophy Type 3; SMA; Spinal Muscular Atrophy Type 2
• Interventions: Drug: Apitegromab; Drug: Nusinersen; Drug: Risdiplam

• Registration Number: NCT07047144
• Lead Sponsor: Scholar Rock, Inc.

Brief Summary

This double-blind, Phase 2, multiple-dose study will be conducted to evaluate the PK/PD, efficacy, safety, and tolerability of apitegromab in subjects \<2 years old with 5q autosomal recessive SMA who have delayed motor milestones for their age attributed to SMA at the discretion of the Investigator or a Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score \<55.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-04-16
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-23
• Last Update Submitted: 2025-06-23
• Study First Posted: 2025-07-02
• Last Update Posted: 2025-07-02
• Study Start: 2025-09-01
• Primary Completion: 2028-11
• Study Completion: 2029-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. Is <2 years old at the time of the informed consent
2. Had a gestational age of ≥35 weeks and gestational body weight ≥2.0 kg at birth
3. Has confirmed diagnosis of 5q autosomal recessive SMA
4. Has confirmed presence of SMN2 gene copy(ies)
5. Must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam)
6. Body weight for age is no less than 1st percentile based on the WHO Child Growth Standards at the Screening Visit
7. Has delayed motor milestones for age attributed to SMA at the discretion of the Investigator or a CHOP-INTEND score <55

Exclusion Criteria

1. Nutritional status that is not anticipated to be stable throughout the study or medical necessity for a gastric feeding tube, where most feeds are administered by this route
2. Major orthopedic issues such as severe scoliosis or severe contractures or interventional procedure, including spine or hip surgery, which is considered to have the potential to substantially limit the ability of the subject to be evaluated on any motor function outcome measures, within 6 months before Screening or anticipated during the study
3. Any other physical limitations (eg, the subject requires cast for contractures) that would prevent the subject from undergoing motor function outcome measures throughout the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Apitegromab low dose + SMN Therapy	Apitegromab	Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
Apitegromab low dose + SMN Therapy	Nusinersen	Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
Apitegromab low dose + SMN Therapy	Risdiplam	Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
Apitegromab high dose + SMN Therapy	Apitegromab	Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
Apitegromab high dose + SMN Therapy	Nusinersen	Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).
Apitegromab high dose + SMN Therapy	Risdiplam	Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).

Primary Outcome Measures

Name	Time	Method
Evaluate the PK of apitegromab in subjects <2 years old with SMA	52 Weeks	Apitegromab concentrations in serum
Evaluate the PD of apitegromab in subjects <2 years old with SMA	52 Weeks	Total latent myostatin concentrations in serum
Evaluate the motor function outcomes (ie, efficacy) due to apitegromab treatment	48 Weeks	Change from baseline in the raw score of the Bayley Scale of Infant and Toddler Development, Fourth Edition - Gross Motor Subscale (BSID-4 GMS) at 48 weeks. BSID-4 GMS is a standardized assessment commonly used to evaluate development across 5 domains in infants and young children. It consists of 58 items, scored from 0 to 2 for each item, with higher scores indicating better gross motor development.

Secondary Outcome Measures

Name	Time	Method
Assess the safety and tolerability of apitegromab administered to subjects receiving an SMN therapy	52 Weeks	Incidence of TEAEs and SAEs by severity