NUSINERSEN for Spinal Muscular Atrophy

Inclusion criteria

• {"criterion_text":"- Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation"}
• {"criterion_text":"- Willing to stop risdiplam treatment"}
• {"criterion_text":"- Willing and able to start treatment with HD nusinersen"}
• {"criterion_text":"- Diagnosis of later-onset SMA with symptom onset at age >6 months."}
• {"criterion_text":"- Aged ≥15 to ≤50 years at the time of informed consent"}
• {"criterion_text":"- Body weight >20 kg"}
• {"criterion_text":"- Received oral risdiplam per the approved label or per the managed access program as follows 1.\tNusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment 2.\tNusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment"}
• {"criterion_text":"- Able to perform the age-appropriate functional assessments in the study"}
• {"criterion_text":"- RULM entry item A score ≥3"}
• {"criterion_text":"- RULM total score ≥5 and ≤30 at Screening"}
• {"criterion_text":"- Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support"}

Exclusion criteria

• {"criterion_text":"- Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration"}
• {"criterion_text":"- Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period"}
• {"criterion_text":"- Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter"}
• {"criterion_text":"- Permanent tracheostomy or permanent ventilation at Screening"}
• {"criterion_text":"- The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening"}
• {"criterion_text":"- History of bacterial meningitis, viral encephalitis, or hydrocephalus"}
• {"criterion_text":"- Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures."}
• {"criterion_text":"- Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study"}
• {"criterion_text":"- Treatment with an investigational drug, biological agent, or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA. Note: Other protocol defined Inclusion/Exclusion criteria may apply."}

Primary endpoints

• {"endpoint_text":"- Change in Total Revised Upper Limb Module (RULM) Score [ Time Frame: Up to Day 855 ]","definition_or_measurement_approach":"Change in the total Revised Upper Limb Module (RULM) score measured up to Day 855 (assessment of motor function using the RULM instrument)."}

Secondary endpoints

• {"endpoint_text":"- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 1695 ]","definition_or_measurement_approach":"Count of participants experiencing AEs and SAEs recorded up to Day 1695."}
• {"endpoint_text":"- Number of Participants With Change in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry from Baseline [ Time Frame: Up to Day 1695 ]","definition_or_measurement_approach":"Count of participants with changes from baseline in clinical laboratory parameters, ECG, vital signs and pulse oximetry, assessed up to Day 1695."}

Methods

• Posters and patient recruitment materials (K2_OUS Poster documents and other recruitment arrangement documents)
• Site-based recruitment through participating hospitals/clinics/universities (contacts listed at trial sites)

Germany

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

591

Number Of Sites

4

Number Of Participants

14

Hungary

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

12-01-2026

Processing Time Days

581

Number Of Sites

1

Number Of Participants

3

Italy

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

14-01-2026

Processing Time Days

583

Number Of Sites

4

Number Of Participants

5

Primary sponsor

Full Name

Biogen Idec Research Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

PPD Development LP

Responsibilities

Pharmacokinetic sample testing

Name

Pharmaceutical Product Development LLC

Third parties

• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"ECG & PFT","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":"Azenta US Inc.","duties_or_roles":"Sample long storage ex Europe","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Pharmacokinetic sample testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Blueprint Genetics Inc.","duties_or_roles":"SMA gene testing and SMN count (for eligibility confirmation)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","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":"Q Squared Solutions LLC","duties_or_roles":"Risdeplam pharmacokinetic sample testing). Lab testing/Kit building/sample storage - Americas only","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Study equipment supply","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"Video storage of videotaped physical assessments","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 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":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Lab kit building, sample storage for ex-US countries","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Questionnaire licenses, scales and translations","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient travel and reimbursement","organisation_type":"Non-Pharmaceutical company"}