(Later-Onset) Spinal Muscular Atrophy neurological muscle disease
Conditions
Interventions
Treatment Period:
High dose of the study medicine will be 20 mg/kg and low dose will be 2 mg/kg.
Doses will be diluted in normal saline and administered via IV over 2 hours +
10-minute window. If t
Sponsors
Scholar Rock Inc.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age 5 through 21 years old at the time of screening for Cohorts 1 and 2; Age 2 years old at the time of screening for Cohort 3 2. Estimated life expectancy >2 years from screening 3. 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 patients parent or legal guardian and patients oral or written assent obtained, if applicable and in accordance with the regulatory and legal requirements of the participating location 4. Documented diagnosis of 5q SMA 5. Diagnosed as later onset (e.g., Type 2 or Type 3) SMA prior to receiving any treatment with therapy approved for SMA 6. Non ambulatory 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 World Health Organization (WHO) motor milestones definition at screening. 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. 7. Ambulatory patients must have the ability to independently ambulate without aids or orthotics over 10 meters at screening 8. For Cohort 1, Revised Hammersmith Scale (RHS) score no greater than 63 at screening 9. For Cohorts 2 and 3, Hammersmith Functional Motor Scale Expanded (HFMSE) score no less than 10 at screening 10. Receiving the same background SMA therapy (e.g., on an approved survival motor neuron (SMN) upregulator therapy such as nusinersen, or not on any SMA therapy) for at least 6 months prior to screening and anticipated to remain on that therapy throughout the duration of the study a. If receiving the SMN upregulator therapy nusinersen, must have completed the loading regimen and initiated maintenance dosing (i.e., completed at least one maintenance dose) with at least 4 weeks after the first maintenance dose having elapsed prior to screening 11. Nutritional status stable over the past 6 months and anticipated to be stable throughout the duration of the study 12. Have no physical limitations that would prevent the patient from undergoing motor function outcome measures throughout the duration of the study 13. Able to receive study drug infusions and provide blood samples through the use of a peripheral intravenous (IV) or a long-term IV access device that the patient has placed for reasons independent from the study (i.e., for background medical care and not for the purpose of receiving SRK-015 in the study), throughout the duration of the study 14. Able to adhere to the requirements of the protocol, including travel to the study center and completing all study procedures and study visits 15. For patients who are expected to have reached reproductive maturity by the end of the study, adhere to study specific contraception requirements a. Females of childbearing potential (see Section 10.1.7.4 for definition) must have a negative pregnancy test at screening and agree to employ highly effective contraceptive measures (failure rate of 1% or less per year when used consistently and correctly) for the duration of the study and for 18 weeks following the last dose of study drug. Effect
Exclusion criteria
Exclusion criteria: 1. Use of tracheostomy with positive pressure 2. Use of chronic daytime non invasive ventilatory support for >16 hours daily in the 2 weeks prior to dosing, or anticipated to regularly receive such daytime ventilator support chronically over the duration of the study 3. Any acute or comorbid condition interfering with the well being of the patient within 14 days of screening, including active systemic infection, the need for acute treatment or inpatient observation due to any reason 4. Severe scoliosis and/or contractures at screening. Based on clinical judgment, any scoliosis or contractures present must be stable over the past 6 months, anticipated to be stable for the duration of the study and not prevent the patient from being evaluated on any functional outcome measures throughout the duration of the study. 5. Pregnant or breastfeeding 6. 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 functional outcome measures, within 6 months prior to screening, or anticipated for the duration of the study 7. Prior history of a hypersensitivity reaction to a monoclonal antibody (mAb) or recombinant protein bearing an Fc domain (such as a soluble receptor-Fc fusion protein), SRK-015, or excipients of SRK-015 8. Use of systemic corticosteroids within 60 days prior to screening. Inhaled or topical steroids are allowed. 9. Treatment with investigational drugs within 3 months or 5 half-lives, whichever is longer prior to screening 10. Use of therapies with potentially significant muscle effects (such as androgens, insulin-like growth factor, growth hormone, systemic beta-agonist, botulinum toxin, or muscle relaxants or muscle-enhancing supplements) or potentially significant neuromuscular effects (such as acetylcholinesterase inhibitors) other than approved SMN upregulator therapy within 60 days prior to screening. 11. Use of valproic acid within 60 days prior to screening. 12. Patient has any other condition, which in the opinion of the Investigator may compromise safety or compliance, would preclude the patient from successful completion of the study, or interfere with the interpretation of the results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: Cohort 1 (Ambulatory Type 3 Patients): Primary Efficacy Endpoint: - Change from Baseline in the RHS total score at Day 364 (Visit 15) Cohort 2 (Type 2 and nonambulatory Type 3 patients) and Cohort 3 (Type 2 patients): Primary Efficacy Endpoint: - Change from Baseline in HFMSE total score at Day 364 (Visit 15) Safety: Safety will be evaluated based on occurrence of or changes in the following parameters: - Treatment-emergent adverse events (TEAEs) and SAEs - Vital signs, including blood pressure, heart rate, body temperature, and respiratory rate - Height and weight - Physical examinations - Laboratory assessments (hematology, serum chemistry, coagulation, urinalysis) - 12 lead electrocardiogram (ECG) - Concomitant medications Safety assessments may be revised if any important safety signals emerge from any ongoing clinical studies (including this study). | — |
Secondary
| Measure | Time frame |
|---|---|
| Cohort 1 (Ambulatory Type 3 Patients) Secondary Efficacy Endpoints: - Change from Baseline in the RHS total score at other prespecified timepoints - Proportion of patients achieving various magnitudes of change in RHS score from Baseline - Change from Baseline in 6 Minute Walk Test (6MWT) - Change from Baseline in 30 Second sit to stand - Change from Baseline in 10 Meter Walk/Run (from the RHS) - Change from Baseline in timed rise from floor (from the RHS) Tertiary Endpoints: - Change from Baseline in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI CAT) - Change from Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue Questionnaire Cohort 2 (Type 2 and nonambulatory Type 3 Patients) and Cohort 3 (Type 2 Patients) : Secondary Efficacy Endpoints: - Change from Baseline in HFMSE total score at other prespecified timepoints - Proportion of patients achieving various magnitudes of change in HFMSE score from Baseline - Change from Baseline in Revised Upper Limb Module (RULM) total score - Change from Baseline in number of WHO motor development milestones attained - Proportion of patients achieving various magnitudes of change in RULM score from Baseline - Proportion of patients who attain a new WHO motor development milestone relative to Baseline Tertiary Endpoints: - Change from Baseline in Time to limitation on Endurance Shuttle Nine Hole Peg Test (ESNHPT) or Endurance Shuttle Box and Block Test (ESBBT) - Change from Baseline in PEDI-CAT - Change from Baseline in PROMIS Fatigue Questionnaire Additional Tertiary Endpoint for Cohort 3: - Time to therapeutic effect (described in the Statistical Analysis Plan [SAP]) as compared between low and high dose of the study medicine arms | — |
Countries
Netherlands
Outcome results
None listed