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    Summary
    EudraCT Number:2021-005314-34
    Sponsor's Protocol Code Number:SRK-015-003
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2022-02-14
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2021-005314-34
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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
    A.3.2Name or abbreviated title of the trial where available
    SAPPHIRE
    A.4.1Sponsor's protocol code numberSRK-015-003
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05156320
    A.5.4Other Identifiers
    Name:INDNumber:136872
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorScholar Rock, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportScholar Rock, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationScholar Rock, Inc.
    B.5.2Functional name of contact pointClinical Information Desk
    B.5.3 Address:
    B.5.3.1Street Address301 Binney Street, 3rd Floor
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1857259 3860
    B.5.6E-mailclinops@scholarrock.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2115
    D.3 Description of the IMP
    D.3.1Product nameApitegromab
    D.3.2Product code SRK-015
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApitegromab
    D.3.9.1CAS number 2278276-46-1
    D.3.9.2Current sponsor codeSRK-015
    D.3.9.4EV Substance CodeSUB193232
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Spinal Muscular Atrophy (SMA)
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy (SMA)
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10041583
    E.1.2Term Spinal muscular atrophy, unspecified
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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
    E.2.2Secondary objectives of the trial
    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
    E.2.3Trial contains a sub-study No
    E.3Principal 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.
    E.4Principal 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
    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy: Change from Baseline in HFMSE total score at 12 months
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months
    E.5.2Secondary 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
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to the protocol
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United Kingdom
    United States
    Belgium
    France
    Germany
    Italy
    Netherlands
    Poland
    Spain
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months8
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 183
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 143
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 40
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 21
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    informed consent document signed by the patient’s parent or legal guardian and patient’s oral or written assent obtained
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 88
    F.4.2.2In the whole clinical trial 204
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients will be offered the option to enter an extension trial when they complete the Treatment Period or if they are still participating in the trial if it is stopped for early efficacy or at the time the Main Efficacy Population completes the trial. Patients must meet the extension trial eligibility criteria before enrolling in the extension trial.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-06-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-09-21
    P. End of Trial
    P.End of Trial StatusCompleted
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