Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
- Conditions
- Spinal Muscular AtrophyNeuromuscular DiseasesAtrophyMuscular Atrophy, SpinalAnti-myostatinSpinal Muscular Atrophy Type 3Spinal Muscular Atrophy Type 2SMAMuscular AtrophyNeuromuscular Manifestations
- Interventions
- Drug: Placebo
- Registration Number
- NCT05156320
- Lead Sponsor
- Scholar Rock, Inc.
- Brief Summary
This Phase 3 trial (Study SRK-015-003) was conducted in patients ≥2 years old at Screening, who were previously diagnosed with later-onset spinal muscular atrophy (SMA) (i.e., Type 2 and Type 3 SMA) and were receiving an approved survival motor neuron (SMN) upregulator therapy (i.e., either nusinersen or risdiplam), to confirm the efficacy and safety of apitegromab as an adjunctive therapy to nusinersen and evaluate the efficacy and safety of apitegromab as an adjunctive therapy to risdiplam.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 188
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Males and females 2 through 21 years old at Screening.
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Documented diagnosis of 5q SMA.
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Diagnosed with later-onset SMA (i.e., Type 2 and Type 3 SMA) before receiving an approved SMN upregulator therapy (i.e., either nusinersen or risdiplam).
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Must be Nonambulatory at Screening. Nonambulatory 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.
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Receiving one background therapy for SMA (i.e., either nusinersen or risdiplam) for the time period specified below and anticipated to remain on that same treatment throughout the trial:
- If receiving the SMN upregulator therapy nusinersen, must have completed at least 10 months of dosing (i.e., completed the loading regimen and at least 2 maintenance doses) before Screening;
- If receiving the SMN upregulator therapy risdiplam, must have completed at least 6 months of dosing before Screening.
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Motor Function Score (HFMSE) ≥10 and ≤45 at Screening.
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Have no physical limitations that would prevent the patient from undergoing motor function outcome measures throughout the duration of the study.
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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.
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Able to adhere to the requirements of the protocol, including travel to the study center and completing all study procedures and study visits.
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For patients who are expected to have reached reproductive maturity by the end of the study, adhere to study specific contraception requirements.
- Received ZOLGENSMA® (onasemnogene abeparvovec-xioi) at any time and previous treatment with apitegromab.
- Use of invasive ventilation and tracheostomy.
- 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 7 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), apitegromab, or excipients of apitegromab.
- 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 beta-agonist, botulinum toxin, or muscle relaxants or muscle-enhancing supplements) or potentially significant neuromuscular effects (such as acetylcholinesterase inhibitors) within 60 days prior to screening.
- Nutritional status not stable over the past 6 months and not anticipated to be stable throughout the duration of the study.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Main Efficacy Population (Apitegromab 10 mg/kg) Apitegromab Type 2 SMA and Nonambulatory Type 3 SMA, ages 2 through 12 years old at Screening. Participants were randomized to receive apitegromab 10 mg/kg for up to 52 weeks. Main Efficacy Population (Apitegromab 20 mg/kg) Apitegromab Type 2 SMA and Nonambulatory Type 3 SMA, ages 2 through 12 years old at Screening. Participants were randomized to receive apitegromab 20 mg/kg for up to 52 weeks. Main Efficacy Population (Placebo) Placebo Type 2 SMA and Nonambulatory Type 3 SMA, ages 2 through 12 years old at Screening. Participants were randomized to receive placebo for up to 52 weeks. Exploratory Subpopulation (Apitegromab) Apitegromab Type 2 SMA and Nonambulatory Type 3 SMA, ages 13 through 21 years old at Screening. Participants were randomized to receive apitegromab 20 mg/kg for up to 52 weeks. Exploratory Subpopulation (Placebo) Placebo Type 2 SMA and Nonambulatory Type 3 SMA, ages 13 through 21 years old at Screening. Participants were randomized to receive placebo for up to 52 weeks.
- Primary Outcome Measures
Name Time Method Main Efficacy Population: Change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) total score. Baseline up to 12 months. The HFMSE assesses the physical abilities of patients with Type 2 and Type 3 SMA. It comprises of 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. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function.
- Secondary Outcome Measures
Name Time Method Main Efficacy Population: Change from Baseline in Revised Upper Limb Module (RULM) total score. Baseline up to 12 months. 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. Higher scores increased great upper limb function.
Main Efficacy Population: Proportion of patients with ≥3-point change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) total score. Baseline up to 12 months. The HFMSE assesses the physical abilities of patients with Type 2 and Type 3 SMA. It comprises of 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. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate increased motor function.
Main Efficacy Population: Change from Baseline in number of WHO motor development milestones attained at 12 months. Baseline up to 12 months. Main Efficacy Population and Exploratory Subpopulation combined: Incidence of Treatment Emergent Adverse Events (TEAEs) and Severe Adverse Events (SAEs) by severity. Baseline up to 12 months. Main Efficacy Population and Exploratory Subpopulation combined: Apitegromab concentrations in serum from blood samples. Baseline up to 12 months. Main Efficacy Population and Exploratory Subpopulation combined: Circulating latent myostatin concentrations in blood samples. Baseline up to 12 months. Main Efficacy Population and Exploratory Subpopulation combined: Presence or absence of ADA against apitegromab in serum from blood samples. Baseline up to 12 months.
Trial Locations
- Locations (50)
Oregon Health & Sciences University
🇺🇸Portland, Oregon, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Children's Medical Center Dallas
🇺🇸Dallas, Texas, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
IRCCS Istituto Giannina Gaslini
🇮🇹Genoa, Italy
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
University of Wisconsin School of Medicine and Public Health
🇺🇸Madison, Wisconsin, United States
Centro Clinico Nemo Pediatrico Policlinico A. Gemelli-Università Cattolica Sacro Cuore
🇮🇹Roma, Italy
The Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milan, Italy
Uniwersyteckie Centrum Kliniczne w Gdańsku
🇵🇱Gdańsk, Poland
Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznań, Poland
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Gillette Children's Specialty Healthcare
🇺🇸Saint Paul, Minnesota, United States
Chr de La Citadelle
🇧🇪Liège, Belgium
Childrens Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
CHU Lille - Hôpital Jeanne de Flandre
🇫🇷Lille, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Dr. von Haunersches Kinderspital
🇩🇪Munich, Germany
Foundation I.R.C.C.S. Carlo Besta Neurological Institute
🇮🇹Milan, Italy
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Instytut Pomnik - Centrum Zdrowia Dziecka: CZD Warszawa
🇵🇱Warsaw, Poland
Hôpital Armand Trousseau, I-Motion
🇫🇷Paris, France
Rady's Children's Hospital/UCSD
🇺🇸San Diego, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
Columbia University, SMA Clinical Research Center
🇺🇸New York, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
CHU Toulouse - Hopital des Enfants
🇫🇷Toulouse, France
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
A.O.U Policlinico G. Martino
🇮🇹Messina, Italy
Hospital Sant Joan de Déu
🇪🇸Barcelona, Spain
Hospital Universitario y Politécnico La Fe
🇪🇸Valencia, Spain
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
🇬🇧London, United Kingdom
University of Oxford
🇬🇧Oxford, United Kingdom
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States