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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by Biogen
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT02386553
First received: February 27, 2015
Last updated: December 23, 2016
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Spinal Muscular Atrophy
Drug: Nusinersen
Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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.

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]
    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 868 ]
  • Change from Baseline in vital signs [ Time Frame: Up to Day 868 ]
    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. [ Time Frame: Up to Day 778 ]

Estimated Enrollment: 25
Study Start Date: May 2015
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nusinersen
Nusinersen administered as an intrathecal injection
Drug: Nusinersen
Solution for intrathecal injection
Other Names:
  • ISIS 396443
  • BIIB058
  • ISIS SMNRx

  Eligibility

Ages Eligible for Study:   up to 6 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02386553

Contacts
Contact: Biogen medinfo@biogen.com

  Show 20 Study Locations
Sponsors and Collaborators
Biogen
Ionis Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Biogen
  More Information

Additional Information:
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02386553     History of Changes
Other Study ID Numbers: 232SM201  2014-002098-12 
Study First Received: February 27, 2015
Last Updated: December 23, 2016

Keywords provided by Biogen:
NURTURE

Additional relevant MeSH terms:
Atrophy
Muscular Atrophy, Spinal
Muscular Atrophy
Pathological Conditions, Anatomical
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on January 19, 2017