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

NCT03921528 | Completed Phase 2 Results FDA Drug

• 1 other identifier: SRK-015-002
• Study Type: interventional
• Target: 58
• Locations: 4 countries
• Sites: 16

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.

Conditions

Spinal Muscular Atrophy; Spinal Muscular Atrophy Type 3; Spinal Muscular Atrophy Type 2; SMA; Neuromuscular Diseases; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal; Neuromuscular Manifestations

Outcome Measures

Primary Outcomes (2)

• Cohort 1: Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Day 364 (Visit 15) [Month 12]

  The Revised Hammersmith Scale (RHS) is a 36 item clinical assessment of physical abilities in patients with Type 2 SMA and ambulatory or nonambulatory patients with Type 3 SMA. For the ambulatory Type 3 patients 5-21 years of age in Cohort 1 (N=23), the primary endpoint was the change from baseline in RHS total score at month 12. The RHS has a minimum achievable score of 0 and a maximum achievable score of 69. The RHS includes 33 items that are graded on a scale of 0, 1, 2, where 0 denotes the lowest level and 2 denotes the highest level of ability/function. The remaining 3 items are scored 0 or 1, where 0 denotes an inability and 1 denotes an ability to achieve. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement.

  Baseline up to 12 months

• Cohort 2 and Cohort 3: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score at Day 364 (Visit 15) [Month 12]

  Cohort 2: For the nonambulatory Type 2 and Type 3 patients 5-21 years of age in Cohort 2 (N=15), the primary efficacy endpoint was the change from baseline in HFMSE total score at month 12. Cohort 3: For the nonambulatory Type 2 patients ≥2 years of age in Cohort 3 (N=20), the primary efficacy endpoint was the change from baseline in HFMSE total score at month 12. The Hammersmith Functional Motor Scale Expanded (HFMSE) assesses the physical abilities of patients with Type 2 and Type 3 SMA comprises 33 items graded on a scale of 0, 1, or 2, where 0 denotes unable, 1 denotes performed with modification or adaptation, and 2 denotes performed without modification or adaptation.

  Baseline up to 12 months

Secondary Outcomes (11)

• Cohort 1:Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Other Prespecified Timepoints

  Baseline to 12 months

• Cohort 1: Proportion of Patients Achieving Various Magnitudes of Change in RHS Score From Baseline

  Baseline to 12 months

• Cohort 1: Change From Baseline in 6-Minute Walk Test (6MWT)

  Baseline to 12 months

• Cohort 1: Change From Baseline in 30-Second Sit-to-Stand

  Baseline to 12 months

• Cohort 1: Change From Baseline in 10-Meter Walk/Run (From RHS)

  Baseline to 12 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

Ambulatory Type 3 SMA

Biological: SRK-015

Cohort 2

EXPERIMENTAL

Type 2 SMA / Non-Ambulatory Type 3 SMA

Biological: SRK-015

Cohort 3

EXPERIMENTAL

Type 2 SMA

Biological: SRK-015

Interventions

SRK-015 BIOLOGICAL

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.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Scholar Rock, Inc.: lead

Study Sites (16)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

The Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Childrens Medical Center Dallas

Dallas, Texas, 75235, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Centro Clinico Nemo Pediatrico Policlinico A. Gemelli-Università Cattolica Sacro Cuore

Roma, Italy

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584, Netherlands

Location

Hospital Sant Joan de Déu

Barcelona, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Publications (1)

• Crawford TO, Darras BT, Day JW, Dunaway Young S, Duong T, Nelson LL, Barrett D, Song G, Bilic S, Cote S, Sadanowicz M, Iarrobino R, Xu TJ, O'Neil J, Rossello J, Place A, Kertesz N, Nomikos G, Chyung Y. Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study. Neurology. 2024 Mar 12;102(5):e209151. doi: 10.1212/WNL.0000000000209151. Epub 2024 Feb 8.

  PMID: 38330285 DERIVED

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Neuromuscular Diseases; Muscular Atrophy; Atrophy; Neuromuscular Manifestations

Interventions

apitegromab

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Results Point of Contact

• Title: Clinical Trials Coordinator
• Organization: Scholar Rock

clinicaltrials@scholarrock.com

833-724-7625

Study Officials

• Thomas O. Crawford, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Active treatment, randomized, double-blind for Cohort 3
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 19, 2019
• Study Start: April 22, 2019
• Primary Completion: January 19, 2021
• Study Completion: February 28, 2024
• Last Updated: December 2, 2024
• Results First Posted: November 17, 2022

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); ES (2); US (11); NL (1)