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Spinal Muscular AtrophyPhase 2TOPAZNCT03921528

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

A Phase 2 study testing SRK-015 in people with Spinal Muscular Atrophy and Spinal Muscular Atrophy Type 3, run by Scholar Rock, Inc. at 16 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 21 years
What is being tested?
SRK-015
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
16 sitesin 4 countries
Study dates
22 Apr 2019to 28 Feb 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

16 sites in 4 countries.

16 sites in 4 countries

United States11 sites
  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • The Johns Hopkins University

    Baltimore, Maryland, 21287

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Childrens Medical Center Dallas

    Dallas, Texas, 75235

  • Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Columbia University

    New York, New York, 10032

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Stanford University

    Palo Alto, California, 94304

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Wake Forest School of Medicine

    Winston-Salem, North Carolina, 27157

Other trials in United States

Italy2 sites
  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, 20162

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

    Roma

Other trials in Italy

Spain2 sites
  • Hospital Sant Joan de Déu

    Barcelona

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

Other trials in Spain

Netherlands1 site
  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584

Other trials in Netherlands

About this study

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)

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.

Being tested
SRK-015
Medical subject headings
Muscular Atrophy, Spinal, Spinal Muscular Atrophies of Childhood, Neuromuscular Diseases, Muscular Atrophy, Atrophy, Neuromuscular Manifestations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SRK-015Biological

    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.

Study groups in NCT03921528
Study groupRoleWhat they receive
Cohort 1ExperimentalAmbulatory Type 3 SMA
Receives: Biological: SRK-015
Cohort 2ExperimentalType 2 SMA / Non-Ambulatory Type 3 SMA
Receives: Biological: SRK-015
Cohort 3ExperimentalType 2 SMA
Receives: Biological: SRK-015

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to 12 months

  2. 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.

    Measured: Baseline up to 12 months

Secondary outcomes (11)
  1. Cohort 1:Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Other Prespecified Timepoints

    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; it has 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.

    Measured: Baseline to 12 months

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

    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; it has 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.

    Measured: Baseline to 12 months

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

    6-Minute Walk Test The 6-Minute Walk Test (6MWT) is an assessment of exercise capacity and fatigue used for ambulatory patients with later-onset SMA who are directed to walk along a 25 meter course as fast as possible over 6 minutes.

    Measured: Baseline to 12 months

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

    The 30-Second Sit-to-Stand Test is an assessment of functional lower-limb strength that measures the maximal number of times a patient can transition from sitting to standing in 30 seconds.

    Measured: Baseline to 12 months

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

    The 10 Meter Walk/Run test is an enhanced function of the RHS used for ambulatory patients with Type 3 SMA. It is a measure of the time taken to walk/run 10 meters. The time to perform is summarized only for patients able to complete the RHS 10-meter walk/run item.

    Measured: Baseline to 12 months

  6. Cohort 1: Change From Baseline in Timed Rise From Floor (From RHS)

    The timed rise from floor test is an enhanced function of the RHS used for ambulatory patients with Type 3 SMA. It is a measure of the time taken to rise to standing from the floor. The time to rise from floor is summarized only for patients able to complete the RHS rise from floor item.

    Measured: Baseline to 12 months

  7. Cohort 2 &3: Change From Baseline in HFMSE Total Score at Other Prespecified Timepoints

    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.

    Measured: Baseline to 12 months

  8. Cohort 2 & 3: Proportion of Patients Achieving Various Magnitudes of Change in HFMSE Score From Baseline

    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.

    Measured: Baseline to 12 months

  9. Cohort 2 & 3: Change in Baseline in Revised Upper Limb Module (RULM) Total Score

    The RULM is a 20 item assessment of upper limb function in nonambulatory patients with SMA that was performed for patients who were 30 months of age or older at baseline. The 19 scored items assess functions that relate to everyday life, such as pressing a button and picking up a token; these items are scored 0, 1, or 2, where 0 denotes unable, 1 denotes able with modification, and 2 denotes able with no modification. The maximum score achievable is 37.

    Measured: Baseline to 12 months

  10. Cohort 2 & 3: Proportion of Patients Achieving a New WHO Motor Development Milestones Relative to Baseline

    The WHO Multicenter Growth Reference Study performance criteria is being utilized to assess the World Health Organization (WHO) motor development milestones of patients with Type 2 and nonambulatory Type 3 SMA enrolled in Cohort 2 and Cohort 3 relative to baseline. The WHO milestone assessment consists of six items which were selected because they have been considered to be universal, fundamental, and simple to test and evaluate, they include 1) sitting without support, 2) hands and knees crawling, 3) standing with assistance, 4) walking with assistance, 5) standing alone, and 6) walking without assistance. Each item is recorded as 1 (unable), 2 (refusal), 3 (Yes) or 9 (did not test). The number of 3s was counted as the final score. The minimum was 0, which means no motor milestones were achieved; the maximum was 6, which means all 6 milestones were achieved.

    Measured: Baseline to 12 months

  11. Cohort 2 & 3: Proportion of Patients Achieving Various Magnitudes of Change in RULM Score From Baseline

    The RULM is a 20 item assessment of upper limb function in nonambulatory patients with SMA that was performed for patients who were 30 months of age or older at baseline. The 19 scored items assess functions that relate to everyday life, such as pressing a button and picking up a token; these items are scored 0, 1, or 2, where 0 denotes unable, 1 denotes able with modification, and 2 denotes able with no modification. The maximum score achievable is 37.

    Measured: Baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2019
  2. Study start22 Apr 2019
  3. Primary completion19 Jan 2021
  4. Study completion28 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03921528
Sponsor's protocol ID
SRK-015-002
Acronym
TOPAZ
Status last verified
Nov 2024
First submitted
16 Apr 2019
Last updated
2 Dec 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38330285

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SRK-015 in people with Spinal Muscular Atrophy and Spinal Muscular Atrophy Type 3, run by Scholar Rock, Inc. at 16 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Italy, Spain, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1: Change From Baseline in the Revised Hammersmith Scale (RHS) Total Score at Day 364 (Visit 15) [Month 12] (time frame: Baseline up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03921528, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2024.

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