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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Apitegromab low dose + SMN Therapy | Experimental | 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). |
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| Apitegromab high dose + SMN Therapy | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apitegromab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the PK of apitegromab in subjects <2 years old with SMA | Apitegromab concentrations in serum | 52 Weeks |
| Evaluate the PD of apitegromab in subjects <2 years old with SMA | Total latent myostatin concentrations in serum | 52 Weeks |
| Evaluate the motor function outcomes (ie, efficacy) due to apitegromab treatment | 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. | 48 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Assess the safety and tolerability of apitegromab administered to subjects receiving an SMN therapy | Incidence of TEAEs and SAEs by severity | 52 Weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Scholar Rock | Contact | 857-259-3860 | MedicalInformation@scholarrock.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Children's Hospital | Recruiting | Phoenix | Arizona | 85016 | United States |
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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.
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| Nusinersen | Drug | Nusinersen is a current standard-of-care SMN therapy that targets the SMN2 gene. It will be administered intrathecally per the prescribing information. |
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| Risdiplam | Drug | Risdiplam is a current standard-of-care SMN therapy that targets the SMN2 gene. It will be administered orally per the prescribing information. |
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| Children's Hospital of Orange County (CHOC) | Recruiting | Orange | California | 92868 | United States |
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| Stanford Neuroscience Health Center (SNHC) | Recruiting | Palo Alto | California | 94304 | United States |
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| Children's Hospital Colorado | Recruiting | Aurora | Colorado | 80045 | United States |
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| Children's Healthcare of Atlanta | Recruiting | Atlanta | Georgia | 30329 | United States |
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| University of Iowa | Recruiting | Iowa City | Iowa | 52242 | United States |
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| Helen DeVos Children's Hospital at Spectrum Health | Recruiting | Grand Rapids | Michigan | 49503 | United States |
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| Atrium Health Wake Forest Baptist | Recruiting | Winston-Salem | North Carolina | 27157 | United States |
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| The Children's Hospital of Philadelphia | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| Le Bonheur Children's Hospital | Not yet recruiting | Memphis | Tennessee | 38103 | United States |
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| University of Texas Southwestern Medical Center | Recruiting | Dallas | Texas | 75207 | United States |
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| Neurology Rare Disease Center | Recruiting | Flower Mound | Texas | 75028 | United States |
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| Cook Children's Medical Center | Recruiting | Fort Worth | Texas | 76104 | United States |
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| Texas Children's Hospital (TCH)-Clinical Care Center (CCC) | Recruiting | Houston | Texas | 77030 | United States |
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| UZ Gent | Recruiting | Ghent | East-Flanders | 9000 | Belgium |
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| UZ Leuven - Campus Gasthuisberg | Recruiting | Leuven | 3000 | Belgium |
| CHR Citadelle | Recruiting | Liège | 4000 | Belgium |
| Hopital Trousseau - I-Motion | Recruiting | Paris | 75012 | France |
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| Fondazione I.R.C.C.S. - Istituto Neurologico Carlo Besta | Recruiting | Milan | 20133 | Italy |
| Centro Clinico NeMO Milano - Fondazione Serena Onlus | Recruiting | Milan | 20162 | Italy |
| Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Recruiting | Rome | 00168 | Italy |
| Universitair Medisch Centrum Utrecht | Recruiting | Utrecht | 3584 CX | Netherlands |
| Hospital Sant Joan de Déu Barcelona | Recruiting | Barcelona | 08950 | Spain |
| Hospital Universitari i Politecnico La Fecnic La Fe | Recruiting | Valencia | 46026 | Spain |
| Leeds General Infirmary Children's Research Department | Recruiting | Leeds | West Yorkshire | LS1 3EX | United Kingdom |
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| ID | Term |
|---|---|
| D009134 | Muscular Atrophy, Spinal |
| D014897 | Spinal Muscular Atrophies of Childhood |
| D020879 | Neuromuscular Manifestations |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D009468 | Neuromuscular Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000722231 | apitegromab |
| C000590926 | nusinersen |
| C000629884 | Risdiplam |
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