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An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy (TOPAZ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03921528
Recruitment Status : Active, not recruiting
First Posted : April 19, 2019
Last Update Posted : March 17, 2021
Sponsor:
Information provided by (Responsible Party):
Scholar Rock, Inc.

Brief Summary:
The TOPAZ study will assess the safety and efficacy of SRK-015 in later-onset Spinal Muscular Atrophy (SMA Type 2 and Type 3) in pediatric and adult patients.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Spinal Muscular Atrophy Type 3 Spinal Muscular Atrophy Type 2 SMA Neuromuscular Diseases Muscular Atrophy Atrophy Muscular Atrophy, Spinal Neuromuscular Manifestations Biological: SRK-015 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: Active treatment, randomized, double-blind for Cohort 3
Primary Purpose: Treatment
Official Title: Phase 2 Active Treatment Study to Evaluate the Efficacy and Safety of SRK-015 in Patients With Later-Onset Spinal Muscular Atrophy (TOPAZ)
Actual Study Start Date : April 22, 2019
Actual Primary Completion Date : January 12, 2021
Estimated Study Completion Date : April 2023


Arm Intervention/treatment
Experimental: Cohort 1
Ambulatory Type 3 SMA
Biological: SRK-015
SRK-015 is a fully human anti-proMyostatin monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda isotype that binds to human pro/latent myostatin with high affinity. SRK-015 will be administered every 4 weeks by intravenous infusion.

Experimental: Cohort 2
Type 2 SMA / Non-Ambulatory Type 3 SMA
Biological: SRK-015
SRK-015 is a fully human anti-proMyostatin monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda isotype that binds to human pro/latent myostatin with high affinity. SRK-015 will be administered every 4 weeks by intravenous infusion.

Experimental: Cohort 3
Type 2 SMA
Biological: SRK-015
SRK-015 is a fully human anti-proMyostatin monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda isotype that binds to human pro/latent myostatin with high affinity. SRK-015 will be administered every 4 weeks by intravenous infusion.




Primary Outcome Measures :
  1. Cohort 1: Change from Baseline in the Revised Hammersmith Scale (RHS) [ Time Frame: Baseline up to 12 months ]
  2. Cohort 2 and Cohort 3: Change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) [ Time Frame: Baseline up to 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Documented diagnosis of 5q SMA.
  • Diagnosed as later-onset (e.g., Type 2 or Type 3) SMA prior to receiving any treatment with therapy approved for SMA.
  • 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.
  • Ambulatory patients must have the ability to independently ambulate without aids or orthotics over 10 meters in 30 seconds or less at screening.
  • 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.

    • 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.
  • Nutritional status stable over the past 6 months and anticipated to be stable throughout the duration of the study.
  • Have no physical limitations that would prevent the patient from undergoing motor function outcome measures throughout the duration of the study.
  • 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 throughout the duration of the study.
  • Able to adhere to the requirements of the protocol, including travel to the study center and completing all study procedures and study visits.
  • For patients who are expected to have reached reproductive maturity by the end of the study, adhere to study specific contraception requirements.

Exclusion Criteria:

  • Use of tracheostomy with positive pressure.
  • 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.
  • 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.
  • 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.
  • Pregnant or breastfeeding.
  • 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.
  • 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).
  • Use of systemic corticosteroids within 60 days prior to screening. Inhaled or topical steroids are allowed.
  • Treatment with investigational drugs within 3 months prior to screening.
  • Use of therapies with potentially significant muscle effects (such as androgens, insulin-like growth factor, growth hormone, systemic betaagonist, botulinum toxin, or muscle relaxants) or muscle-enhancing supplements within 60 days prior to screening.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03921528


Locations
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United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Maryland
The Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, New York
Columbia University
New York, New York, United States, 10032
United States, North Carolina
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States, 27157
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
Childrens Medical Center Dallas
Dallas, Texas, United States, 75235
United States, Virginia
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507
Italy
ASST Grande Ospedale Metropolitano Niguarda
Milano, Italy, 20162
Centro Clinico Nemo Pediatrico Policlinico A. Gemelli-Università Cattolica Sacro Cuore
Roma, Italy
Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584
Spain
Hospital Sant Joan de Déu
Barcelona, Spain
Hospital Universitari i Politecnic La Fe
Valencia, Spain, 46026
Sponsors and Collaborators
Scholar Rock, Inc.
Investigators
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Principal Investigator: Thomas O. Crawford, MD Johns Hopkins University
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Responsible Party: Scholar Rock, Inc.
ClinicalTrials.gov Identifier: NCT03921528    
Other Study ID Numbers: SRK-015-002
First Posted: April 19, 2019    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Neuromuscular Diseases
Neuromuscular Manifestations
Spinal Muscular Atrophies of Childhood
Atrophy
Pathological Conditions, Anatomical
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn