A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 15 May 2023
• Main ID: NCT02386553
• Date of registration: 27/02/2015
• Prospective Registration: Yes
• Primary sponsor: Biogen
• Public title: A Study of Multiple Doses of Nusinersen (ISIS 396443) Delivered to Infants With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy NURTURE
• Scientific title: An Open-Label Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Subjects With Genetically Diagnosed and Presymptomatic Spinal Muscular Atrophy
• Date of first enrolment: May 18, 2015
• Target sample size: 25
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02386553
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Prevention. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Canada, Germany, Israel, Italy, Qatar, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- Age = 6 weeks at first dose.

- Genetic documentation of 5q SMA homozygous gene deletion or mutation or compound
heterozygous mutation.

- Genetic documentation of 2 or 3 copies of survival motor neuron 2 (SMN2).

- Ulnar compound muscle action potential (CMAP) = 1 mV at Baseline.

- Gestational age of 37 to 42 weeks for singleton births; gestational age of 34 to 42
weeks for twins.

- Meet additional study related criteria.

Key Exclusion Criteria:

- Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or
respiratory support).

- Any clinical signs or symptoms at Screening or immediately prior to the first dosing
(Day 1) that are, in the opinion of the Investigator, strongly suggestive of SMA.

- Clinically significant abnormalities in hematology or clinical chemistry parameters.

- Treatment with an investigational drug given for the treatment of SMA biological
agent, or device. Any history of gene therapy, prior antisense oligonucleotide (ASO)
treatment, or cell transplantation.

- Meet additional study related criteria.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.



Age minimum: N/A
Age maximum: 6 Weeks
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Drug: Nusinersen

Primary Outcome(s)

Time to death or respiratory intervention [Time Frame: Up to Day 2891]

Secondary Outcome(s)

Change from Baseline in clinical laboratory parameters [Time Frame: Up to Day 2891]

Change from Baseline in electrocardiograms (ECGs) [Time Frame: Up to Day 2891]

Change from Baseline in chest circumference ratio [Time Frame: Up to Day 2891]

Percentage of participants alive [Time Frame: At 13 months, and 2, 3, 4, 5, 6, 7 and 8 years of age]

Percentage of participants who attained motor milestones assessed as part of the Hammersmith Infant Neurological Examination (HINE) [Time Frame: At 13 and 24 months of age]

Change from Baseline in head circumference [Time Frame: Up to Day 2891]

Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) [Time Frame: Up to Day 2891]

Change from Baseline in neurological examinations [Time Frame: Up to Day 2891]

Change from Baseline in head to chest circumference ratio [Time Frame: Up to Day 2891]

Percentage of participants developing clinically manifested spinal muscular atrophy (SMA) [Time Frame: At 13 and 24 months of age]

Percentage of participants who attained motor milestones as assessed by World Health Organization (WHO) criteria [Time Frame: Up to Day 2891]

Change from Baseline in vital signs [Time Frame: Up to Day 2891]

Change from Baseline in weight for age/length [Time Frame: Up to Day 2891]

Cerebrospinal fluid (CSF) and plasma Nusinersen concentrations [Time Frame: Up to Day 2801]

Change from Baseline in arm circumference ratio [Time Frame: Up to Day 2891]

Change from Baseline in the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) motor function scale [Time Frame: Up to Day 2891]

Incidence of adverse events (AEs) and/or serious adverse events (SAEs) [Time Frame: Up to Day 2891]

Secondary ID(s)

232SM201

2014-002098-12

Source(s) of Monetary Support

Please refer to primary and secondary sponsors