A clinical study of a new possible treatment in patients with type 2 or 3 Spinal Muscular Atrophy

• Register: EUCTR
• Last refreshed on: 12 October 2021
• Main ID: EUCTR2018-004383-65-NL
• Date of registration: 03/04/2019
• Prospective Registration: Yes
• Primary sponsor: Scholar Rock, Inc.
• Public title: A clinical study of a new possible treatment in patients with type 2 or 3 Spinal Muscular Atrophy
• Scientific title: Phase 2 Active Treatment Study to Evaluate the Efficacy and Safety of SRK-015 in Patients with Later-Onset Spinal Muscular Atrophy - The TOPAZ study
• Date of first enrolment: 30/10/2019
• Target sample size: 58
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004383-65
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Cohort 1 and 2 are open label and Cohort 3 is double blind randomized; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: For Cohort 3: two different doses (2 and 20 Mg/kg) of the study drug; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy, Netherlands, Spain, United States

Contacts

• Name: Bente Kristiansen
• Affiliation: Medpace UK

• Name: Bente Kristiansen
• Affiliation: Medpace UK

Key inclusion & exclusion 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 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 18 weeks following the last dose of study drug. Effective contraception methods are restricted to combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral,
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 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), 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: SRK-015
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Apitegromab
Current Sponsor code: SRK-015
Other descriptive name: HUMAN ANTI-PROMYOSTATIN MONOCLONAL ANTIBODY
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: SRK-015
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Apitegromab
Current Sponsor code: SRK-015
Other descriptive name: HUMAN ANTI-PROMYOSTATIN MONOCLONAL ANTIBODY
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: For both the Treatment Periods and Extension Period:
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 SRK015
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

Main Objective: For both the Treatment Period and Extension Periods:
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 in 3 separate predefined cohorts

Timepoint(s) of evaluation of this end point: Ongoing throughout the study

Primary end point(s): Cohort 1; Ambulatory Type 3 patients:
Change from Baseline in the revised Hammersmith Scale (RHS) total score at Day 364 (Visit 15).
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) total Score at Day 364 (Visit15). HFMSE is designed for SMA, validated in SMA, and considered clinically meaningful.

Secondary Outcome(s)

Secondary end point(s): Cohort 1; Ambulatory Type 3 patients:
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)

Cohort 2 and Cohort 3;Type 2 and non ambulatory Type 3 patients:
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)
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

Timepoint(s) of evaluation of this end point: Ongoing throughout the study

Secondary ID(s)

SRK-015-002

NCT03921528

Source(s) of Monetary Support

Scholar Rock, Inc.

Ethics review

Status: Approved
Approval date: 30/10/2019
Contact: