Anti-myostatin, Neuromuscular Manifestations, SMA, Spinal Muscular Atrophy, Spinal Muscular Atrophy Type 2, Spinal Muscular Atrophy Type 3
Conditions
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.
Interventions
DRUGApitegromab
Apitegromab is a fully human anti-proMyostatin monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda isotype that specifically binds to human pro/latent myostatin with high affinity inhibiting myostatin activation. SRK-015 will be administered every 4 weeks by intravenous (IV) infusion.
DRUGNusinersen
Nusinersen is a current standard-of-care SMN therapy that targets the SMN2 gene. It will be administered intrathecally per the prescribing information.
DRUGRisdiplam
Risdiplam is a current standard-of-care SMN therapy that targets the SMN2 gene. It will be administered orally per the prescribing information.
Sponsors
Scholar Rock, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Sponsor, the subject's caregiver, Investigators, and site personnel, with the exception of the designated unblinded personnel (eg, site Pharmacist), will be blinded to the treatment assignment.
Eligibility
Sex/Gender
ALL
Age
No minimum to 2 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Assess the safety and tolerability of apitegromab administered to subjects receiving an SMN therapy | 52 Weeks | Incidence of TEAEs and SAEs by severity |
Countries
Belgium, France, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
CONTACTScholar Rock
Outcome results
None listed