Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy (ENDEAR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT02193074
First received: July 14, 2014
Last updated: March 24, 2017
Last verified: March 2017
  Purpose
The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset SMA. The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.

Condition Intervention Phase
Spinal Muscular Atrophy
Drug: nusinersen
Procedure: Sham procedure
Phase 3

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile-onset Spinal Muscular Atrophy

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Percentage of participants who attained motor milestones as assessed by Section 2 of Hammersmith Infant Neurological Examination (HINE) [ Time Frame: Up to Day 402 ]
  • Time to death or respiratory intervention [ Time Frame: Up to Day 402 ]

Secondary Outcome Measures:
  • Percentage of participants who attained Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) [ Time Frame: Up to Day 402 ]
    CHOP-INTEND tests includes 16 items structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.

  • Overall Survival Rate [ Time Frame: Up to Day 402 ]
  • Percentage of participants not requiring permanent ventilation [ Time Frame: Up to Day 402 ]
  • Percentage of participants who attained Compound Muscular Action Potential (CMAP) [ Time Frame: Up to Day 402 ]
    CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. Participants with peroneal CMAP amplitude increasing to or maintained at ≥ 1 mV.

  • Time to death or respiratory intervention in the subgroups of participants below the study median disease duration [ Time Frame: Up to Day 402 ]
  • Time to death or respiratory intervention in the subgroups of participants above the study median disease duration [ Time Frame: Up to Day 402 ]
  • Number of participants experiencing Adverse events (AEs) [ Time Frame: Up to Day 402 ]
  • Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to Day 402 ]
  • Number of participants with clinically significant weight abnormalities [ Time Frame: Up to Day 402 ]
  • Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to Day 402 ]
  • Number of participants with clinically significant physical examination abnormalities [ Time Frame: Up to Day 402 ]
  • Number of participants with clinically significant laboratory assessment abnormalities [ Time Frame: Up to Day 402 ]
  • Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities [ Time Frame: Up to Day 402 ]
  • Change from Baseline in concomitant medications [ Time Frame: Up to Day 402 ]

Enrollment: 122
Study Start Date: July 2014
Study Completion Date: November 2016
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nusinersen Drug: nusinersen
Administered by intrathecal (IT) injection as specified in the treatment arm.
Other Names:
  • ISIS 396443
  • BIIB058
  • Spinraza
  • IONIS-SMN Rx
  • ISIS SMNRx
Sham Comparator: Sham procedure Procedure: Sham procedure
Small needle prick on the lower back at the location where the IT injection is normally made

Detailed Description:

This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc..

In August 2016, sponsorship of the trial was transferred to Biogen.

  Eligibility

Ages Eligible for Study:   up to 210 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Be born (gestational age) between 37 and 42 weeks
  • Be medically diagnosed with spinal muscular atrophy (SMA)
  • Have Survival Motor Neuron2 (SMN2) Copy number = 2
  • Body weight equal to or greater than 3rd percentile for age using appropriate country-specific guidelines
  • Be able to follow all study procedures
  • Reside within approximately 9 hours ground-travel distance from a participating study center, for the duration of the study

Key Exclusion Criteria:

  • Hypoxemia Oxygen (O2) saturation awake less than 96% or O2 saturation asleep less than 96%, without ventilation support) during screening evaluation
  • Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Site Investigator, at the Screening visit that would render the participant unsuitable for participation in the study
  • Participant's parent or legal guardian is not willing to meet standard of care guidelines (including vaccinations and respiratory syncytial virus prophylaxis if available), nor provide nutritional and respiratory support throughout the study

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: NCT02193074

  Show 31 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Additional Information:
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02193074     History of Changes
Other Study ID Numbers: ISIS 396443-CS3B
2013-004422-29 ( EudraCT Number )
Study First Received: July 14, 2014
Last Updated: March 24, 2017

Keywords provided by Biogen:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
ISIS-SMN Rx
ISIS 396443
IONIS-SMNRx
IONIS-SMN Rx
Spinraza
ENDEAR

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 May 24, 2017