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Active, not recruitingNCT05626855ONYXUpdated Sep 1, 2026

Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab

A Phase 3 interventional study of Apitegromab in Spinal Muscular Atrophy, Spinal Muscular Atrophy Type 3 and Spinal Muscular Atrophy Type 2, sponsored by Scholar Rock, Inc.. Active, not recruiting at 49 sites in 9 countries. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2026-09-01.

Sponsored by Scholar Rock, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
238
Allocation
Not applicable
Ages
2 Years and older
Sex
All
01

Study summary

The ONYX study is an Open-Label, Multicenter, Extension study that will evaluate the long-term safety and efficacy of Apitegromab in Patients with Type 2 and Type 3 SMA who have completed TOPAZ or SAPPHIRE.

02

Conditions studied

  • Spinal Muscular Atrophy
  • Spinal Muscular Atrophy Type 3
  • Spinal Muscular Atrophy Type 2
  • SMA
  • Neuromuscular Diseases
  • Muscular Atrophy
  • Atrophy
  • Muscular Atrophy, Spinal
  • Neuromuscular Manifestations
  • Anti-myostatin
03

Who can participate

Ages eligible
2 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial. (For TOPAZ, completed is defined as completion of Visit EC14 in Extension Period C or participating in TOPAZ at the time the trial is ended. For SAPPHIRE, completed is defined as completion of Visit 14 or participating in SAPPHIRE at the time the trial is ended)
  • Estimated life expectancy >2 years from the Baseline Visit (Day 1)
  • 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
  • Able to adhere to the requirements of the protocol, including travel to the trial site and completing all trial procedures and trial visits
  • Females of childbearing potential must have a negative pregnancy test at the Baseline Visit and agree to use at least 1 highly effective method of contraception throughout the trial and for 20 weeks after the last dose of apitegromab

Exclusion criteria

Exclusion Criteria:

  • Patient permanently discontinued study treatment during the feeder trial (i.e., TOPAZ or SAPPHIRE)
  • 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
  • Patient is currently enrolled in any investigational drug trial other than TOPAZ or SAPPHIRE
  • Prior history of severe hypersensitivity reaction or intolerance to SMN-targeted therapies
  • Prior history of severe hypersensitivity reaction or intolerance to apitegromab
  • 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
  • Any acute or comorbid condition interfering with the well-being of the patient at the patient's last visit in TOPAZ or SAPPHIRE, (including active systemic infection, the need for acute treatment, or inpatient observation due to any reason). After resolution of the condition, the patient can be enrolled in the trial if they meet all the other eligibility criteria.
  • Pregnant or breastfeeding
  • 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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
238 participants (actual)

Study arms

  • Experimental
    Treatment Period

    Patients who are ≥2 years of age with Type 2 and Type 3 SMA will receive apitegromab 20 mg/kg every 4 weeks by intravenous (IV) infusion during the 104-week Treatment Period

    Drug: Apitegromab

Interventions

  • DrugApitegromab

    Apitegromab (SRK-015) is an investigational, fully human immunoglobulin G4 monoclonal antibody that specifically binds to human proforms (i.e., inactive precursor forms) of myostatin, pro- and latent- myostatin, with high affinity, inhibiting activation of myostatin, a negative regulator of muscle growth and strength.

05

What researchers measure

Primary outcomes

  1. Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA

    Incidence of TEAEs and SAEs by severity

    Time frame: Up to 6 years

Secondary outcomes

  1. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

    Hammersmith Functional Motor Scale Expanded (HFMSE) total score at prespecified time points (excludes ambulatory patients)

    Time frame: Up to 6 years

  2. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

    Revised Upper Limb Module (RULM) total score at prespecified time points (excludes ambulatory patients)

    Time frame: Up to 6 years

  3. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

    Number of World Health Organization (WHO) motor development milestones attained at prespecified time points (excludes ambulatory patients)

    Time frame: Up to 6 years

  4. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

    Revised Hammersmith Scale (RHS) total score

    Time frame: Up to 6 years

  5. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

    Results for 6-Minute Walk Test

    Time frame: Up to 6 years

  6. Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

    30-Second Sit-to-Stand

    Time frame: Up to 6 years

  7. Further evaluate the immunogenicity of apitegromab

    Presence or absence of antidrug antibody (ADA) against apitegromab in serum from blood samples

    Time frame: Up to 6 years

Other outcomes

  1. Further characterize the PK of apitegromab

    Apitegromab concentrations in serum from blood samples at prespecified time points

    Time frame: Up to 6 years

  2. Further evaluate the pharmacodynamic (PD) effects of apitegromab

    Total latent myostatin concentrations in blood samples at prespecified time points

    Time frame: Up to 6 years

  3. To further evaluate the effect of apitegromab on patient/caregiver-reported disability, and fatigability.

    Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) at prespecified time points

    Time frame: Up to 6 years

  4. To further evaluate the effect of apitegromab on patient/caregiver-reported disability, and fatigability.

    Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue Questionnaire at prespecified time points

    Time frame: Up to 6 years

  5. To further evaluate the effect of apitegromab on patient/caregiver-reported disability, and fatigability.

    Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) at prespecified time points

    Time frame: Up to 6 years

06

Study locations

49 sites
  • Phoenix Childrens Hospital
    Phoenix, Arizona 85016, United States
  • UCSD Altman Clinical and Translational Research
    La Jolla, California 92037, United States
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
  • Stanford Neuroscience Health Center
    Palo Alto, California 94304, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • Nemours Biomedical Research
    Orlando, Florida 32827, United States
  • Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
  • University of Iowa
    Iowa City, Iowa 52242, United States
  • University of Kansas Medical Center
    Fairway, Kansas 66205, United States
  • Johns Hopkins Hospital
    Baltimore, Maryland 21287, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • Helen DeVos Children's Hospital
    Grand Rapids, Michigan 49503, United States
  • Gillette Children's Specialty Healthcare
    Saint Paul, Minnesota 55101, United States
  • Washington University Medical Campus
    St Louis, Missouri 63110, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • Wake Forest University School of Medicine
    Winston-Salem, North Carolina 27157, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43215, United States
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
  • The Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • St. Jude Children's Research Hospital
    Memphis, Tennessee 38105, United States
  • University of Texas Southwestern - Pediatric Neurology
    Dallas, Texas 75207, United States
  • University of Utah
    Salt Lake City, Utah 84112, United States
  • Children's Specialty Group PLLC (Children's Hospital of The King's Daughters)
    Newport News, Virginia 23606, United States
  • Seattle Children's Hospital
    Seattle, Washington 98115, United States
  • University of Wisconsin Hospital
    Madison, Wisconsin 53792, United States
  • UZ Gent
    Ghent, 9000, Belgium
  • UZ Leuven
    Leuven, 3000, Belgium
  • CHR Citadelle
    Liège, 4000, Belgium
  • CHRU de Lille - Hpital Jeanne de Flandre
    Lille, 59037, France
  • Hopital Trousseau - I-Motion
    Paris, 75012, France
  • CHU Toulouse Hopital des Enfants
    Toulouse, 31059, France
  • Universitätskinderklinik Bonn, Abteilung für Neuropädiatrie und SPZ
    Bonn, 53127, Germany
  • Universitatsklinikum Essen
    Essen, 45147, Germany
  • Universitatsklinikum Freiburg
    Freiburg im Breisgau, 79106, Germany
  • Klinikum der Universitat Munchen, Dr. von Haunersches Kinderspital, Abteilung fur Kinderneurologie und Entwicklungsneurologie
    Munchen, Bayern, 80337, Germany
  • Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative
    Genova, 16147, Italy
  • UOC NEUROLOGIA E MALATTIE NEUROMUSCOLARI A.O.U Policlinico G. Martino
    Messina, 98125, Italy
  • Carlo Besta Neurological Research Institute
    Milan, 20133, Italy
  • NeuroMuscular Omnicentre
    Milan, 20162, Italy
  • Fondazione Policlinico Universitario A. Gemelli
    Roma, 106, Italy
  • UMC Utrecht
    Utrecht, 3508, Netherlands
  • Uniwersyteckie Centrum Kliniczne
    Gdansk, 80-211, Poland
  • Uniwersytecki Szpital Kliniczny w Poznaniu, Oddział Kliniczny Neurologii Dzieci i Młodzieży
    Poznan, 60-355, Poland
  • Instytut Pomnik - Centrum Zdrowia Dziecka
    Warsaw, 04-730, Poland
  • Hospital Sant Joan de Deau
    Barcelona, 08950, Spain
  • Hospital Universitari i Politecnic La Fe
    Valencia, 46026, Spain
  • Leeds Children's Hospital Clinical Research
    Leeds, LS1 3EX, United Kingdom
  • Great Ormond Street Hospital for Children
    London, WC1N 1EH, United Kingdom
  • University of Oxford
    Oxford, OX3 0ER, United Kingdom
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05626855
Lead sponsor
Scholar Rock, Inc.
Responsible party
Sponsor
First posted
Nov 25, 2022
Start date
Apr 17, 2023
Primary completion
Nov 1, 2026 (estimated)
Completion
May 2, 2029 (estimated)
Last update
Sep 1, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.

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