Nusinersen for Spinal Muscular Atrophy

Inclusion criteria

• {"criterion_text":"- Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol"}

Exclusion criteria

• {"criterion_text":"- Treatment with another investigational therapy or enrollment in another interventional clinical study"}
• {"criterion_text":"- Treatment with an approved therapy for SMA after the Day 302 Visit of Study 232SM203 (NCT04089566). Note: Other protocol defined Inclusion/Exclusion criteria may apply."}

Primary endpoints

• {"endpoint_text":"- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; counts of participants experiencing AEs and SAEs as recorded during study follow-up."}
• {"endpoint_text":"- Change from Baseline in Growth Parameters [ Time Frame: Up to Day 1921 ]..","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in growth parameters (as measured at scheduled visits)."}
• {"endpoint_text":"- Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; assessment of shifts from baseline in clinical laboratory parameter results."}
• {"endpoint_text":"- Number of Participants With Shifts from Baseline in Electrocardiogram (ECG) [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; recording shifts from baseline in ECG findings."}
• {"endpoint_text":"- Number of Participants With Shifts from Baseline in Vital Signs [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; assessment of changes from baseline in vital sign measurements."}
• {"endpoint_text":"- Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in aPTT laboratory measurements."}
• {"endpoint_text":"- Change from Baseline in Prothrombin Time (PT) [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in PT laboratory measurements."}
• {"endpoint_text":"- Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in INR laboratory measurements."}
• {"endpoint_text":"- Change from Baseline in Urine Total Protein [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in urine total protein."}
• {"endpoint_text":"- Change from Baseline in Neurological Examination Outcomes for Participants ≤2 Years of Age [ Time Frame: Up to Day 1921].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in neurological exam outcomes for participants ≤2 years."}
• {"endpoint_text":"- Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in neurological exam outcomes for participants >2 years."}
• {"endpoint_text":"- Percentage of Participants With A Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; proportion of participants with platelet counts below LLN on ≥2 consecutive postbaseline measurements."}
• {"endpoint_text":"- Percentage of Participants With a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of >500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of >60 msec [ Time Frame: Up toDay 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; percentage of participants meeting QTcF safety thresholds (>500 ms and increase >60 ms from baseline) at any postbaseline timepoint."}

Secondary endpoints

• {"endpoint_text":"- Total Number of New World Health Organization (WHO) Motor Milestones [ Time Frame: Up to Day 1921]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; count of new WHO motor milestones achieved."}
• {"endpoint_text":"- Number of Participants Who Used Respiratory Support, by Type [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; number of participants using respiratory support categorized by type."}
• {"endpoint_text":"- Number of Hours Per Day of Respiratory Support [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; average/recorded hours per day of respiratory support use."}
• {"endpoint_text":"- Number of Days That Respiratory Support Is Used [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; number of days with respiratory support use."}
• {"endpoint_text":"- Time to Death (Overall Survival) [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; time-to-event analysis for overall survival."}
• {"endpoint_text":"- Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in CHOP INTEND total score."}
• {"endpoint_text":"- Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in HINE Section 2 motor milestone scores."}
• {"endpoint_text":"- Percentage of HINE Section 2 Motor Milestone Responders [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; proportion of participants meeting predefined response criteria on HINE Section 2."}
• {"endpoint_text":"- Percentage of Time Spent on Ventilation [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; percentage of time participants spend on mechanical ventilation."}
• {"endpoint_text":"- Time to Death or Permanent Ventilation [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; time-to-event for death or requirement for permanent ventilation."}
• {"endpoint_text":"- Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score [ Time Frame: Up to Day 1921 ].","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in HFMSE score."}
• {"endpoint_text":"- Change from Baseline in Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 1921 ]..","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in RULM score."}
• {"endpoint_text":"- Change From Baseline in Plasma Levels of Neurofilament (NF) [ Time Frame: Up to Day 1921 ]","definition_or_measurement_approach":"Time Frame: Up to Day 1921; change from baseline in plasma neurofilament levels measured by laboratory assay."}

Germany

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

70

Number Of Sites

2

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

29-07-2024

Processing Time Days

102

Number Of Sites

2

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

18-04-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

70

Number Of Sites

3

Number Of Participants

18

Primary sponsor

Full Name

Biogen Idec Research Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

IQVIA Limited

Responsibilities

Site Start-up & Management, Project & Vendor Management; various trial operational activities (codes 1,11,12,2,6,15 listed)

Name

Pharmaceutical Product Development LLC (PPD)

Responsibilities

Clinical trial services (entries listed with code 7 and code 8 for related PPD entities); responsibilities include trial operations and submissions (specific text not provided for some entries)

Name

PPD Development LP

Responsibilities

Pharmacokinetic sample testing

Name

Suvoda LLC

Responsibilities

IVRS30 - treatment randomisation

Name

Medidata Solutions Inc.

Third parties

• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"PT Assessment Tools & Video storage of videotaped physical assessments","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Pharmacokinetic sample testing","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long term storage of PK, Immunogenicity, and Biomarker/pNFH Plasma and CSF samples (EU and others)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"EAC endpoint adjudication committee for pulmonary assessment","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Site Start-up & Management, Project & Vendor Management","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Study equipment supply","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Drug labelling, packaging, shipping & import","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"PPD Global Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Serology/endocrinology, Analytical chemistry, Lab kit building, Sample storage","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Praxis Communications LLC","duties_or_roles":"Patient recruitment and retention materials","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Questionnaire licenses, PedsQL, scales and translations","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"Immunogenicity testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient travel costs reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long term storage of PK, Immunogenicity, and Biomarker/pNFH Plasma and CSF samples (ex EU)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"IVRS30 - treatment randomisation","organisation_type":"Non-Pharmaceutical company"}