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

NCT05626855 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: SRK-015-004
• Study Type: interventional
• Target: 238
• Locations: 9 countries
• Sites: 49

Brief 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.

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; Anti-myostatin

Outcome Measures

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

  Up to 6 years

Secondary Outcomes (7)

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

  Up to 6 years

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

  Up to 6 years

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

  Up to 6 years

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

  Up to 6 years

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

  Up to 6 years

Other Outcomes (5)

• Further characterize the PK of apitegromab

  Up to 6 years

• Further evaluate the pharmacodynamic (PD) effects of apitegromab

  Up to 6 years

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

  Up to 6 years

Study Arms (1)

Treatment Period

EXPERIMENTAL

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

Apitegromab DRUG

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.

Treatment Period

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Scholar Rock, Inc.: lead

Study Sites (49)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

UCSD Altman Clinical and Translational Research

La Jolla, California, 92037, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Stanford Neuroscience Health Center

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Biomedical Research

Orlando, Florida, 32827, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Johns HopkinsHospital

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

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Washington University Medical Campus

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43215, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern - Pediatric Neurology

Dallas, Texas, 75207, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Children's Specialty Group PLLC (Children's Hospital of The King's Daughters)

Newport News, Virginia, 23606, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98115, United States

Location

University of Wisconsin Hospital

Madison, Wisconsin, 53792, United States

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHR Citadelle

Liège, 4000, Belgium

Location

CHRU de Lille - Hpital Jeanne de Flandre

Lille, 59037, France

Location

Hopital Trousseau - I-Motion

Paris, 75012, France

Location

CHU Toulouse Hopital des Enfants

Toulouse, 31059, France

Location

Universitätskinderklinik Bonn, Abteilung für Neuropädiatrie und SPZ

Bonn, 53127, Germany

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Klinikum der Universitat Munchen, Dr. von Haunersches Kinderspital, Abteilung fur Kinderneurologie und Entwicklungsneurologie

Munchen, Bayern, 80337, Germany

Location

Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative

Genova, 16147, Italy

Location

UOC NEUROLOGIA E MALATTIE NEUROMUSCOLARI A.O.U Policlinico G. Martino

Messina, 98125, Italy

Location

Carlo Besta Neurological Research Institute

Milan, 20133, Italy

Location

NeuroMuscular Omnicentre

Milan, 20162, Italy

Location

Fondazione Policlinico Universitario A. Gemelli

Roma, 106, Italy

Location

UMC Utrecht

Utrecht, 3508, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-211, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu, Oddział Kliniczny Neurologii Dzieci i Młodzieży

Poznan, 60-355, Poland

Location

Instytut Pomnik - Centrum Zdrowia Dziecka

Warsaw, 04-730, Poland

Location

Hospital Sant Joan de Deau

Barcelona, 08950, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Leeds Children's Hospital Clinical Research

Leeds, LS1 3EX, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 1EH, United Kingdom

Location

University of Oxford

Oxford, OX3 0ER, United Kingdom

Location

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open Label Extension Study

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 25, 2022
• Study Start: April 17, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): May 2, 2029
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); IT (5); GB (3); US (25); BE (3); PL (3); FR (3); NL (1); ES (2)