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

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ClinicalTrials.gov Identifier: NCT02386553
Recruitment Status : Active, not recruiting
First Posted : March 12, 2015
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE February 27, 2015
First Posted Date  ICMJE March 12, 2015
Last Update Posted Date October 30, 2019
Actual Study Start Date  ICMJE May 20, 2015
Estimated Primary Completion Date February 25, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2019)
Time to death or respiratory intervention [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
Time to death or respiratory intervention [ Time Frame: Up to Day 868 ]
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.
Change History Complete list of historical versions of study NCT02386553 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2019)
  • Percentage of participants developing clinically manifested spinal muscular atrophy (SMA). [ Time Frame: At 13 and 24 months of age ]
  • Percentage of participants alive [ Time Frame: At 13 months, and 2, 3, 4, 5 and 8 years of age ]
  • Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE) [ Time Frame: At 13 and 24 months of age ]
  • Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in weight for age/length [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in head circumference [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in chest circumference ratio [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in head to chest circumference ratio [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in arm circumference ratio [ Time Frame: Up to Day 2891 ]
  • Incidence of adverse events (AEs) and/or serious adverse events (SAEs) [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in clinical laboratory parameters [ Time Frame: 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) [ Time Frame: Up to Day 2891 ]
  • Change from Baseline in vital signs [ Time Frame: Up to Day 2891 ]
    Vital sign will be assessed by: temperature, pulse rate, resting systolic and diastolic blood pressure, and respiratory rate.
  • Change from Baseline in neurological examinations [ Time Frame: Up to Day 2891 ]
  • Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations. [ Time Frame: Up to Day 2801 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
  • Percentage of participants developing clinically manifested spinal muscular atrophy (SMA). [ Time Frame: At 13 and 24 months of age ]
  • Percentage of participants alive [ Time Frame: At 13 and 24 months of age ]
  • Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE) [ Time Frame: At 13 and 24 months of age ]
  • Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in weight for age/length [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in head circumference [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in chest circumference [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in arm circumference [ Time Frame: At 13 and 24 months of age ]
  • Change from Baseline in head to chest circumference ratio [ Time Frame: At 13 and 24 months of age ]
  • Incidence of adverse events (AEs) and/or serious adverse events (SAEs) [ Time Frame: Up to Day 868 ]
  • Change from Baseline in clinical laboratory parameters [ Time Frame: Up to Day 868 ]
  • Change from Baseline in electrocardiograms (ECGs) [ Time Frame: Up to Day 868 ]
  • Change from Baseline in vital signs [ Time Frame: Up to Day 868 ]
  • Cerebrospinal fluid (CSF) and plasma ISIS SMNRx (ISIS 396443) concentrations. [ Time Frame: Up to Day 778 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
Official Title  ICMJE 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.
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE Drug: Nusinersen
Solution for intrathecal injection
Other Names:
  • ISIS 396443
  • BIIB058
  • ISIS SMNRx
  • Spinraza
Study Arms  ICMJE Experimental: Nusinersen
Nusinersen administered as an intrathecal injection
Intervention: Drug: Nusinersen
Publications * Finkel RS, Chiriboga CA, Vajsar J, Day JW, Montes J, De Vivo DC, Yamashita M, Rigo F, Hung G, Schneider E, Norris DA, Xia S, Bennett CF, Bishop KM. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016 Dec 17;388(10063):3017-3026. doi: 10.1016/S0140-6736(16)31408-8. Epub 2016 Dec 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 6, 2015)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 25, 2025
Estimated Primary Completion Date February 25, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 6 Weeks   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Germany,   Italy,   Qatar,   Taiwan,   Turkey,   United States
Removed Location Countries Argentina,   Israel,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT02386553
Other Study ID Numbers  ICMJE 232SM201
2014-002098-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP