An Open-label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01703988
• Date of registration: 08/10/2012
• Prospective Registration: No
• Primary sponsor: Biogen
• Public title: An Open-label Safety, Tolerability and Dose-Range Finding Study of Multiple Doses of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy
• Scientific title: An Open-Label, Dose Escalation Study to Assess the Safety, Tolerability and Dose-Range Finding of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Spinal Muscular Atrophy
• Date of first enrolment: October 2012
• Target sample size: 34
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01703988
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Medical Director
• Affiliation: Biogen

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- Genetic documentation of 5q SMA (homozygous gene deletion or mutation)

- Clinical signs attributable to SMA

- Able to complete all study procedures, measurements, and visits and parent/patient has
adequately supportive psychosocial circumstances, in the opinion of the Investigator

- Estimated life expectancy > 2 years from Screening

- Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is
planned for study procedure

Key Exclusion Criteria:

- Respiratory insufficiency defined by the medical necessity for invasive or
non-invasive ventilation during a 24-hour period

- Medical necessity for a gastric feeding tube, where the majority of feeds are given by
this route, as assessed by the Investigator

- Previous scoliosis surgery that would interfere with the lumbar puncture injection
procedure

- Hospitalization for surgery (e.g. scoliosis surgery) or pulmonary event within 2
months of screening or planned during the duration of the study

- Presence of an untreated or inadequately treated active infection requiring systemic
antiviral or antimicrobial therapy at any time during the screening period

- History of brain or spinal cord disease that would interfere with lumbar puncture
procedures or cerebrospinal fluid (CSF) circulation

- Presence of an implanted shunt for the drainage of CSF or an implanted central nervous
system catheter

- History of bacterial meningitis

- Dosing with ISIS 396443 in clinical study ISIS 396443-CS1 Cohorts 2, 3, or 4

- Dosing with ISIS 396443 in clinical study ISIS 396443-CS10

- Clinically significant abnormalities in hematology or clinical chemistry parameters or
electrocardiogram (ECG) at the Screening visit, as assessed by the Site Investigator
that would render the subject unsuitable for inclusion

- Treatment with investigational drug, biological agent, or device within 1-month of
Screening or 5 half-lives of study agent, whichever is longer. Treatment with
valproate or hydroxyurea within 3-months of screening. Any history of gene therapy or
cell transplantation

- Ongoing medical condition that would interfere with the conduct and assessments of the
study. Examples are medical disability (e.g. wasting or cachexia, severe anemia) that
would interfere with the assessment of safety or would compromise the ability of the
patient to undergo study procedures.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.



Age minimum: 2 Years
Age maximum: 15 Years
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy

Intervention(s)

Drug: Nusinersen

Primary Outcome(s)

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Discontinuations Due to AEs, and Highest Severity of AEs [Time Frame: Participants were followed for the duration of the study; mean (SD) duration of treatment was 82.9 (15.4) days]

Secondary Outcome(s)

Urine Pharmacokinetics: Renal Clearance, Cohort 4 [Time Frame: Day 1 and Day 85]

Plasma Pharmacokinetics: Plasma Pharmacokinetics: Area Under the Plasma Concentration Time Curve From the Time of the IT Dose to 6 Hours After Dosing (AUC0-6hr) [Time Frame: Day 1 and Day 85]

Cerebrospinal Fluid (CSF) Pharmacokinetics: Predose CSF Drug Concentrations [Time Frame: Day 1, Day 29, and Day 85]

Plasma Pharmacokinetics: Time to Reach Cmax in Plasma [Time Frame: Day 1 and Day 85]

Plasma Pharmacokinetics: Maximal Observed Plasma Drug Concentration (Cmax) [Time Frame: Day 1 and Day 85]

Secondary ID(s)

2017-000327-27

ISIS 396443 - CS2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/03/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01703988