Later Onset Spinal Muscular Atrophy (SMA) MedDRA version: 20.0 Level: LLT Classification code 10079415 Term: Spinal muscular atrophy type III System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10079416 Term: Spinal muscular atrophy type II System Organ Class: 100000004850
Conditions
Interventions
Product Name: SRK-015
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: SRK-015
Current Sponsor code: SRK-015
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Sponsors
Scholar Rock, Inc.
Eligibility
Sex/Gender
All
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 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 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 in 30 seconds or less 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 10a. 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 15a. Females of childbearing potential 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 12 weeks following the last dose of
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 co morbid 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 judgement, 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 or recombinant protein bearing an Fc domain (such as a soluble receptor-Fc fusion protein) 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 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 within 60 days prior to screening 11. 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 |
|---|---|
| Main Objective: To assess safety and tolerability of SRK-015 in patients with later onset (e.g., Type 2 and Type 3) spinal muscular atrophy (SMA) To assess the efficacy of SRK-015 by assessing changes in motor function outcome measures ;Timepoint(s) of evaluation of this end point: Ongoing throughout the study; Secondary Objective: To characterize the pharmacokinetics (PK) of SRK-015 To evaluate the pharmacodynamic (PD) effects of SRK-015 To evaluate time to therapeutic effect between low and high dose SRK-015 in a predefined cohort (Cohort 3) To evaluate the immunogenicity of SRK-015 To evaluate the effect of SRK-015 on quality of life assessments ; Primary end point(s): Cohort 1; Ambulatory Type 3 patients: Change from Baseline in the revised Hammersmith Scale (RHS). Administration of the RHS includes the timed rise from floor and 10 meter walk/run tests. The RHS is designed for SMA, validated in SMA, and considered clinically meaningful. Cohort 2 and Cohort 3;Type 2 and non ambulatory Type 3 patients: Change from Baseline in Hammersmith Functional Motor Skills Expanded (HFMSE) Scores. HFMSE is designed for SMA, validated in SMA, and considered clinically meaningful. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Ongoing throughout the study; Secondary end point(s): Cohort 1; Ambulatory Type 3 patients: 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) Cohort 2 and Cohort 3;Type 2 and non ambulatory Type 3 patients: Proportion of patients achieving various magnitudes of change in HFMSE score from Baseline Change from Baseline in Revised Upper Limb Module (RULM) 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 | — |
Countries
Canada, Germany, Italy, Netherlands, Spain, United States
Contacts
Public ContactBente Kristiansen
Medpace UK
Outcome results
None listed