A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
- Registration Number
- NCT02386553
- Lead Sponsor
- Biogen
- Brief Summary
The primary objective of the study is to examine the efficacy of multiple doses of Nusinersen administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA). Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic SMA.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
- Age ≤ 6 weeks at first dose.
- Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound heterozygous mutation.
- Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).
- Ulnar compound muscle action potential (CMAP) ≥ 1 mV at Baseline.
- Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42 weeks for twins.
- Meet additional study related criteria.
Key
- Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support).
- Any clinical signs or symptoms at Screening or immediately prior to the first dosing (Day 1) that are, in the opinion of the Investigator, strongly suggestive of SMA.
- Clinically significant abnormalities in hematology or clinical chemistry parameters.
- Treatment with an investigational drug given for the treatment of SMA biological agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.
- Meet additional study related criteria.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nusinersen Nusinersen Nusinersen administered as an intrathecal injection
- Primary Outcome Measures
Name Time Method Time to death or respiratory intervention Up to Day 2891 The time will be the age of the participant at the first occurrence of either a respiratory intervention or death. Respiratory intervention is defined as invasive or noninvasive ventilation for ≥6 hours/day continuously for 7 or more days OR tracheostomy.
- Secondary Outcome Measures
Name Time Method Percentage of participants developing clinically manifested spinal muscular atrophy (SMA) At 13 and 24 months of age Percentage of participants alive At 13 months, and 2, 3, 4, 5, 6, 7 and 8 years of age Change from Baseline in neurological examinations Up to Day 2891 Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE) At 13 and 24 months of age Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria Up to Day 2891 Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale Up to Day 2891 Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Up to Day 2891 Change from Baseline in weight for age/length Up to Day 2891 Change from Baseline in head circumference Up to Day 2891 Change from Baseline in chest circumference ratio Up to Day 2891 Change from Baseline in head to chest circumference ratio Up to Day 2891 Change from Baseline in arm circumference ratio Up to Day 2891 Incidence of adverse events (AEs) and/or serious adverse events (SAEs) Up to Day 2891 Change from Baseline in clinical laboratory parameters Up to Day 2891 Assessed by the following laboratory tests: Hematology: red blood cells, hemoglobin, hematocrit, platelets, white blood cells, white blood cell differential, Blood chemistry: total protein, albumin, creatinine, cystatin C, creatine phosphokinase, blood urea nitrogen, total bilirubin (direct and indirect), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glucose, calcium, phosphorous, chloride, sodium, potassium. Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, red blood cells, white blood cells, epithelial cells, bacteria, casts, crystals
Change from Baseline in electrocardiograms (ECGs) Up to Day 2891 Change from Baseline in vital signs Up to Day 2891 Vital sign will be assessed by: temperature, pulse rate, resting systolic and diastolic blood pressure, and respiratory rate.
Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations Up to Day 2801
Trial Locations
- Locations (25)
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Nemours Children's Hospital, Orlando
🇺🇸Orlando, Florida, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Queensland Children's Hospital
🇦🇺South Brisbane, Queensland, Australia
University of Calgary - Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Fondazione Serena Onlus - Centro Clinico Nemo
🇮🇹Milano, Italy
Hamad General Hospital
🇶🇦Doha, Qatar
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Yeditepe University Medical School Hospital
🇹🇷Istanbul, Turkey
Hospital de Pediatria Dr. J. P. Garrahan
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
University of California Davis Health System
🇺🇸Sacramento, California, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Columbia University
🇺🇸New York, New York, United States
Seattle Children's Research Institute
🇺🇸Seattle, Washington, United States
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Baden-Württemberg, Germany
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Great Ormond Street Hospital for Children
🇬🇧London, Greater London, United Kingdom
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Lazio, Italy