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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02193074
Other study ID # ISIS 396443-CS3B
Secondary ID 2013-004422-29
Status Terminated
Phase Phase 3
First received
Last updated
Start date August 19, 2014
Est. completion date November 21, 2016

Study information

Verified date February 2021
Source Biogen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of the study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally (IT) to participants with infantile-onset with infantile-onset spinal muscular atrophy (SMA). The secondary objective of the study is to examine the safety and tolerability of nusinersen administered intrathecally to participants with infantile-onset SMA.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 122
Est. completion date November 21, 2016
Est. primary completion date November 21, 2016
Accepts healthy volunteers No
Gender All
Age group N/A to 210 Days
Eligibility 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.

Study Design


Intervention

Drug:
nusinersen
Administered by intrathecal (IT) injection as specified in the treatment arm.
Procedure:
Sham procedure
Small needle prick on the lower back at the location where the IT injection is normally made

Locations

Country Name City State
Australia Royal Children's Hospital, Children's Neuroscience Centre Parkville Victoria
Australia Sydney Children's Hospital Sydney New South Wales
Belgium Hôpital Universitaire des Enfants Reine FABIOLA (HUDERF) Brussels
Canada Hospital for Sick Children Toronto Ontario
Canada British Columbia Children's Hospital/UBC Vancouver British Columbia
France Institut de Myologie Paris
Germany Universitatsklinikum Essen Essen
Germany Universtatsklinikum Freiburg, Zentrum fur Kinder-und Jugendmedizin , Abteilung Neuropadiatrie und Muskelerkrankungen Freiburg
Italy Istituto Giannina Gaslini, Centro Traslazionale di Miologia e Patologie Neurodegenerative Genova
Italy Pediatric Neurology Unit, Catholic University Rome
Japan Hyogo College of Medicine Nishinomiya Hyogo
Japan Tokyo Women's Medical University Tokyo
Korea, Republic of Seoul National University Hospital Seoul
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Hospital Universitario La Paz, Pediatric Neurology Department Madrid
Sweden University of Gothenburg, The Queen Silvia Children's Hospital Gothenburg
Turkey Hacettepe Children's Hospital Ankara
United Kingdom UCL Institute of Child Health/Great Ormond Street London
United Kingdom MRC Centre for Neuromuscular Diseases at Newcastle, Institute of Genetic Medicine Newcastle University Newcastle
United States Children's Hospital Colorado Aurora Colorado
United States Boston Children's Hospital Boston Massachusetts
United States Ann and Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States UT Southwestern Medical Center/Children's Medical Center Dallas Dallas Texas
United States Duke Children's Hospital Durham North Carolina
United States UCLA Medical Center Los Angeles California
United States Columbia University Medical Center New York New York
United States Nemours Children's Hospital Orlando Florida
United States Children's Hospital of Philadelphia - Neurology Philadelphia Pennsylvania
United States Doernbecher Children's Hospital Portland Oregon
United States Washington University School of Medicine Saint Louis Missouri
United States Primary Children's Medical Center (University of Utah) Salt Lake City Utah

Sponsors (1)

Lead Sponsor Collaborator
Biogen

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Motor Milestones Responders The definition of a motor milestones responder was based on improvement in the motor milestones categories in Section 2 of the Hammersmith Infant Neurological Examination (HINE), with the exclusion of voluntary grasp, as follows:
(i) subject demonstrates = 2-point increase in the motor milestones category of ability to kick or achievement of maximal score on that category (touching toes), or a 1-point increase in the motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and (ii) among the motor milestone categories, with the exclusion of voluntary grasp, there are more categories where there is improvement as defined in (i) than worsening. (For the category of ability to kick, worsening is defined as = 2-point decrease or decrease to the lowest possible score of no kicking. For the other categories, worsening is defined as = 1-point decrease.) The lowest possible score for the HINE is 0 (zero), and the highest possible score for the HINE is 28.
assessed at the later of the Day 183, Day 302, or Day 394 study visits
Primary Time to Death or Permanent Ventilation Estimated proportion of participants who died or required permanent ventilation by a given study day, based on the Kaplan-Meier product-limit method. Time to death or permanent ventilation was defined as either tracheostomy or = 16 hours ventilation/day continuously for > 21 days in the absence of an acute reversible event. This endpoint was adjudicated by a blinded, independent group of experienced clinicians, the Event Adjudication Committee (EAC), based on review of clinical study data and supporting information. Results are based on all available data. Day 91, Day 182, Day 273, Day 364, Day 394
Secondary Percentage of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) Responders A participants was considered a CHOP-INTEND responder if the change from baseline in CHOP-INTEND total score is = 4 points based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. 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). Total scores range from 0 to 64, with higher scores indicating better movement functioning. Results are based on all available data. assessed at Baseline and the later of the Day 183, Day 302, or Day 394 study visits
Secondary Summary of Time to Death Estimated proportion of participants who died by given duration thresholds, based on the Kaplan-Meier product-limit method. Day 91, Day 182, Day 273, Day 364, Day 394
Secondary Percentage of Participants Not Requiring Permanent Ventilation Up to Day 394
Secondary Percentage of Compound Muscular Action Potential (CMAP) Responders CMAP is an electrophysiological technique that can be used to determine the approximate number of motor neurons in a muscle or group of muscles. A participant was defined as a CMAP responder if the CMAP amplitude at the peroneal nerve was increasing to or maintained at = 1 mV (comparing to the baseline) based on assessment at the later of the Day 183, Day 302, or Day 394 study visits. Results are based on all available data. assessed at the later of the Day 183, Day 302, or Day 394 study visits
Secondary Time to Death or Permanent Ventilation in the Subgroup of Participants Below the Study Median Disease Duration Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants below the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method. Day 91, Day 182, Day 273, Day 364, Day 394
Secondary Time to Death or Permanent Ventilation in the Subgroup of Participants Above the Study Median Disease Duration Estimated proportion of participants who died or required permanent ventilation (EAC-adjudicated events) among participants above the study median disease duration (13.1 weeks), by given duration thresholds, based on the Kaplan-Meier product-limit method. Day 91, Day 182, Day 273, Day 364, Day 394
Secondary Number of Participants Experiencing Adverse Events (AEs), Serious AEs (SAEs) and Discontinuations Due to AEs AE: any unfavorable and unintended sign, symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product. SAE: any AE that in the view of either the Investigator or Sponsor, meets any of the following criteria: results in death; is life threatening: that is, poses an immediate risk of death at the time of the event; requires in-patient hospitalization or prolongation of existing hospitalization; results in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect in the offspring of the participant (whether male or female); is an important medical event in the opinion of the Investigator or Sponsor. Screening through Day 394 (± 7 days) or early termination
Secondary Number of Participants With AEs Corresponding to Changes in Hematology Values up to Day 394 (± 7 days) or early termination
Secondary Number of Participants With AEs Corresponding to Changes in Blood Chemistry Values up to Day 394 (± 7 days) or early termination
Secondary Number of Participants Meeting Selected Vital Sign Criteria Post-Baseline up to Day 394 (± 7 days) or early termination
Secondary Summary of Shifts in 12-lead Electrocardiogram (ECG) Results Shift to 'abnormal, not clinically significant' includes 'unknown' or 'normal' to 'abnormal, not clinically significant'. Shift to 'abnormal, clinically significant' includes 'unknown' or 'normal' to 'abnormal, clinically significant'. up to Day 394 (± 7 days) or early termination
Secondary Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Values up to Day 394 (± 7 days) or early termination
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