A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

Spinal Muscular Atrophy Clinical Trial

— NURTURE  

Official title:

An Open-Label Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Subjects With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02386553
• Other study ID #: 232SM201
• Secondary ID: 2014-002098-12
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 18, 2015
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Weeks to 6 Weeks

Eligibility

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Intervention

Drug:
• Nusinersen
Solution for intrathecal injection

Locations

Country	Name	City	State
Argentina	Hospital de Pediatria Dr. J. P. Garrahan	Ciudad Autonoma Buenos Aires
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Queensland Children's Hospital	South Brisbane	Queensland
Canada	University of Calgary - Alberta Children's Hospital	Calgary	Alberta
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden-Württemberg
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Fondazione Serena Onlus - Centro Clinico Nemo	Milano
Italy	Ospedale Pediatrico Bambino Gesù	Roma	Lazio
Qatar	Hamad General Hospital	Doha
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Yeditepe University Medical School Hospital	Istanbul
United Kingdom	Great Ormond Street Hospital for Children	London	Greater London
United States	Children's Hospital Colorado	Aurora	Colorado
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	David Geffen School of Medicine	Los Angeles	California
United States	Columbia University	New York	New York
United States	Nemours Children's Hospital, Orlando	Orlando	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of California Davis Health System	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Children's Research Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Germany,  Israel,  Italy,  Qatar,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to death or respiratory intervention	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.	Up to Day 2891
Secondary	Percentage of participants developing clinically manifested spinal muscular atrophy (SMA)		At 13 and 24 months of age
Secondary	Percentage of participants alive		At 13 months, and 2, 3, 4, 5, 6, 7 and 8 years of age
Secondary	Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE)		At 13 and 24 months of age
Secondary	Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria		Up to Day 2891
Secondary	Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale		Up to Day 2891
Secondary	Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE)		Up to Day 2891
Secondary	Change from Baseline in weight for age/length		Up to Day 2891
Secondary	Change from Baseline in head circumference		Up to Day 2891
Secondary	Change from Baseline in chest circumference ratio		Up to Day 2891
Secondary	Change from Baseline in head to chest circumference ratio		Up to Day 2891
Secondary	Change from Baseline in arm circumference ratio		Up to Day 2891
Secondary	Incidence of adverse events (AEs) and/or serious adverse events (SAEs)		Up to Day 2891
Secondary	Change from Baseline in clinical laboratory parameters	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	Up to Day 2891
Secondary	Change from Baseline in electrocardiograms (ECGs)		Up to Day 2891
Secondary	Change from Baseline in vital signs	Vital sign will be assessed by: temperature, pulse rate, resting systolic and diastolic blood pressure, and respiratory rate.	Up to Day 2891
Secondary	Change from Baseline in neurological examinations		Up to Day 2891
Secondary	Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations		Up to Day 2801