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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 February 2021
• Main ID: NCT02193074
• Date of registration: 14/07/2014
• Prospective Registration: Yes
• Primary sponsor: Biogen
• Public title: A Study to Assess the Efficacy and Safety of Nusinersen (ISIS 396443) in Infants With Spinal Muscular Atrophy ENDEAR
• Scientific 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
• Date of first enrolment: August 19, 2014
• Target sample size: 122
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02193074
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion 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.



Age minimum: N/A
Age maximum: 210 Days
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Procedure: Sham procedure

Drug: nusinersen

Primary Outcome(s)

Percentage of Motor Milestones Responders [Time Frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits]

Time to Death or Permanent Ventilation [Time Frame: Day 91, Day 182, Day 273, Day 364, Day 394]

Secondary Outcome(s)

Summary of Shifts in 12-lead Electrocardiogram (ECG) Results [Time Frame: up to Day 394 (± 7 days) or early termination]

Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline [Time Frame: up to Day 394 (± 7 days) or early termination]

Number of Participants With AEs Corresponding to Changes in Hematology Values [Time Frame: up to Day 394 (± 7 days) or early termination]

Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration [Time Frame: Day 91, Day 182, Day 273, Day 364, Day 394]

Summary of Time to Death [Time Frame: Day 91, Day 182, Day 273, Day 364, Day 394]

Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs [Time Frame: Screening through Day 394 (± 7 days) or early termination]

Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values [Time Frame: up to Day 394 (± 7 days) or early termination]

Percentage of Compound Muscular Action Potential (CMAP) Responders [Time Frame: assessed at the later of the Day 183, Day 302, or Day 394 study visits]

Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders [Time Frame: assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits]

Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values [Time Frame: up to Day 394 (± 7 days) or early termination]

Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration [Time Frame: Day 91, Day 182, Day 273, Day 364, Day 394]

Percentage of Participants Not Requiring Permanent Ventilation [Time Frame: Up to Day 394]

Secondary ID(s)

2013-004422-29

ISIS 396443-CS3B

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/07/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02193074