Phase 3 Active Treatment Trial to Evaluate the Efficacy and Safety of Apitegromab in Patients with Later-Onset Spinal Muscular Atrophy Who Are Being Treated with Nusinersen or Risdiplam

• Register: EUCTR
• Last refreshed on: 27 January 2025
• Main ID: EUCTR2021-005314-34-NL
• Date of registration: 10/03/2022
• Prospective Registration: Yes
• Primary sponsor: Scholar Rock, Inc.
• Public title: Phase 3 Active Treatment Trial to Evaluate the Efficacy and Safety of Apitegromab in Patients with Later-Onset Spinal Muscular Atrophy Who Are Being Treated with Nusinersen or Risdiplam
• Scientific title: Phase 3, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Apitegromab (SRK-015) in Patients with Later-Onset Spinal Muscular Atrophy Receiving Background Nusinersen or Risdiplam Therapy - SAPPHIRE
• Date of first enrolment: 08/06/2022
• Target sample size: 204
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-005314-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Contacts

• Name: Clinical Information Desk
• Affiliation: Scholar Rock, Inc.

• Name: Clinical Information Desk
• Affiliation: Scholar Rock, Inc.

Key inclusion & exclusion 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 =45 at the Screening Visit
9. No physical limitations that would prevent the patient from undergoing motor function outcome measures throughout the trial
10. Able to receive study drug infusions and provide blood samples through the use of a peripheral IV or a long-term IV access device that the patient has placed for reasons independent from the trial (i.e., for background medical care and not for the purpose of
receiving apitegromab in the trial), throughout the trial
11. Able to adhere to the requirements of the protocol, including travel to the trial site and completing all trial procedures and trial visits
12. Females of childbearing potential must have a negative pregnancy test at Screening and agree to use at least 1 acceptable method of contraception throughout the trial and for 20 weeks after the last dose of study drug. Female patients who are expected to have reached reproductive maturity by the end of the trial must agree to adhere to trial-specific contraception requirements.
Are the trial subjects under 18? yes
Number of subjects for this age range: 183
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 beta-agonist, 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


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Spinal Muscular Atrophy (SMA)
MedDRA version: 20.1 Level: LLT Classification code 10041583 Term: Spinal muscular atrophy, unspecified System Organ Class: 100000004850

Intervention(s)

Product Name: Apitegromab
Product Code: SRK-015
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Apitegromab
CAS Number: 2278276-46-1
Current Sponsor code: SRK-015
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 months

Main Objective: Primary Efficacy: Assess the efficacy of apitegromab compared with placebo using the Hammersmith Functional Motor Scale Expanded (HFMSE) in patients 2 through 12 years old

Primary end point(s): Primary Efficacy: Change from Baseline in HFMSE total score at 12 months

Secondary Objective: Key Secondary Efficacy:
- Assess the efficacy of apitegromab compared with placebo based on the # of patients with clinical improvement in patients 2-12 yrs
- Assess the efficacy of apitegromab compared with placebo by measuring changes in upper limb function using the RULM in patients 2-12 yrs
- Assess the efficacy of apitegromab compared with placebo by measuring changes in # of WHO motor development milestones in patients 2-12 yrs

Other Secondary Efficacy
- Further assess the efficacy of apitegromab compared with placebo by evaluating changes in additional motor function outcome measures and changes in HFMSE at other prespecified timepoints in patients 2-12 yrs

Main Efficacy/Exploratory Subpopulation Combined Secondary (in all randomized patients who receive at least 1 dose of apitegromab):
- Assess safety and tolerability of apitegromab
- Characterize the PK of apitegromab
- Evaluate the PD effects of apitegromab
- Evaluate the immunogenicity of apitegromab

Secondary Outcome(s)

Secondary end point(s): Key Secondary Efficacy:
- 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

Other Secondary Efficacy:
- Proportion of patients achieving various magnitudes of change in HFMSE score from Baseline at 12 months
- Proportion of patients achieving various magnitudes of change in RULM score from Baseline at 12 months
- Proportion of patients who attain a new WHO motor development milestone relative to Baseline at 12 months
- Change from Baseline in HFMSE total score at other prespecified time points
- Change from Baseline in RULM total score at other prespecified time points
- Change from Baseline in number of WHO motor development milestones attained at other prespecified time points

Main Efficacy/Exploratory Subpopulation Combined Secondary
- Incidence of TEAEs and SAEs by severity
- Apitegromab concentrations in serum from blood samples
- Circulating latent myostatin concentrations in blood samples
- Presence or absence of ADA against apitegromab in serum from blood samples

Timepoint(s) of evaluation of this end point: Please refer to the protocol

Secondary ID(s)

2021-005314-34-BE

NCT05156320

SRK-015-003

136872

Source(s) of Monetary Support

Scholar Rock, Inc.

Ethics review

Status: Approved
Approval date: 08/06/2022
Contact: