neuromuscular disease SMA
Conditions
Interventions
• For the Main Efficacy Population, approximately 156 patients who are 2
through 12 years old at Screening will be randomized 1:1:1 double-blind to
receive apitegromab 10 mg/kg, apitegromab 20 mg/kg
Sponsors
Scholar Rock Inc.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Informed consent document signed by the patient if the patient is legally an adult. If the patient is legally a minor, informed consent document signed by the patient's parent or legal guardian and patient's oral or written assent obtained, if applicable and in accordance with the regulatory and legal requirements of the participating location. 2. Males and females 2 through 21 years old at Screening 3. Estimated life expectancy >2 years from Screening 4. Documented diagnosis of 5q SMA 5. Diagnosed with later-onset SMA (i.e., Type 2 and Type 3 SMA) before receiving an approved SMN upregulator therapy (i.e., either nusinersen or risdiplam). Patients who never had the ability to walk independently will be classified as Type 2. Patients who previously had the ability to walk unaided will be classified as Type 3. 6. Must be nonambulatory at Screening. Nonambulatory patients must be able to sit independently (sits up straight with head erect for at least 10 seconds; does not use arms or hands to balance body or support position) per WHO motor milestones at Screening 7. Receiving one background therapy for SMA (i.e., either nusinersen or risdiplam) for the time period specified below and anticipated to remain on that same treatment throughout the trial a. If receiving the SMN upregulator therapy nusinersen, must have completed at least 10 months of dosing (i.e., completed the loading regimen and at least 2 maintenance doses) before Screening b. If receiving the SMN upregulator therapy risdiplam, must have completed at least 6 months of dosing before Screening 8. Motor Function Score (HFMSE) >=10 and
Exclusion criteria
Exclusion criteria: 1. Received ZOLGENSMA® (onasemnogene abeparvovec-xioi) at any time 2. Previous treatment with apitegromab 3. Prior history of severe hypersensitivity reaction or intolerance to SMN upregulator therapies 4. Prior history of a hypersensitivity reaction to a mAb or recombinant protein bearing an Fc domain (e.g., a soluble receptor-Fc fusion protein), apitegromab, or excipients of apitegromab 5. Require invasive ventilation or tracheostomy 6. Nutritional status that was not stable over the past 6 months and is not anticipated to be stable throughout the trial or medical necessity for a gastric/nasogastric feeding tube, where the majority of feeds are given by this route, as assessed by the Investigator 7. Major orthopedic or other interventional procedure, including spine or hip surgery, considered to have the potential to substantially limit the ability of the patient to be evaluated on any motor function outcome measures, within 6 months before Screening or anticipated during the trial 8. Treatment with other investigational drugs in a clinical trial within 3 months or 5 half-lives, whichever is longer, before Screening 9. Use of valproic acid or hydroxyurea within 90 days before Screening 10. Use of therapies with potentially significant muscle effects (e.g., androgens, insulin like growth factor, growth hormone, systemic betaagonist, botulinum toxin, or muscle relaxants or muscle-enhancing supplements) or potentially significant neuromuscular effects (e.g., acetylcholinesterase inhibitors) other than approved SMN upregulator therapy within 60 days before Screening 11. Use of systemic corticosteroids within 60 days before Screening. Inhaled or topical steroids are allowed. 12. Any acute or comorbid condition interfering with the well-being of the patient within 7 days before Screening, including active systemic infection, the need for acute treatment, or inpatient observation due to any reason 13. Severe contractures (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]) or scoliosis (general guideline for Grade 3) at Screening. Based on clinical judgment, any contractures or scoliosis present must be stable over the past 6 months, anticipated to be stable throughout the trial, and not prevent the patient from being evaluated on any motor function outcome measures throughout the trial. 14. Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks before dosing, or anticipated to regularly receive such daytime ventilator support chronically throughout the trial 15. Pregnant or breastfeeding 16. Any other condition or clinically significant laboratory result or ECG value that, in the opinion of the Investigator, may compromise safety or compliance, would preclude the patient from successful completion of the trial, or interfere with the interpretation of the results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in HFMSE total score at 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| -Proportion of patients with >=3-point change from Baseline in the HFMSE total score at 12 months -Change from Baseline in RULM total score at 12 months -Change from Baseline in number of WHO motor development milestones attained at 12 months | — |
Countries
Netherlands
Outcome results
None listed