An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1 (NCT01494701)

• Register: ClinicalTrials.gov
• Last refreshed on: 22 February 2021
• Main ID: NCT01780246
• Date of registration: 28/01/2013
• Prospective Registration: Yes
• Primary sponsor: Biogen
• Public title: An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1 (NCT01494701)
• Scientific title: An Open-label Study to Assess the Safety and Tolerability of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated in ISIS 396443-CS1
• Date of first enrolment: January 31, 2013
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01780246
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- Clinical signs attributable to Spinal Muscular Atrophy

- Satisfactory completion of dosing and all study visits in ISIS 396443-CS1
(NCT01494701) with an acceptable safety profile, per Investigator judgement.

- Able to complete all study procedures, measurements and visits and parent/participant
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:

- Have any new or worsening of existing condition which in the opinion of the
Investigator would make the participant unsuitable for enrollment, or could interfere
with the participant participating in or completing the study.

- Dosing in ISIS 396443-CS1 (NCT01494701) within 270 days (9 months) of screening, or
longer ago than 450 days (15 months)

- Dosing in ISIS 396443-CS2 (NCT01703988)

- Hospitalization for surgery (i.e. 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 any time during the screening period

- Clinically significant abnormalities in hematology or clinical chemistry parameters

- 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 1 months of screening. Any history of gene therapy or
cell transplantation

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 clinically significant physical examination abnormalities [Time Frame: Up to 24 Weeks]

Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [Time Frame: Up to 24 Weeks]

Number of participants with clinically significant laboratory parameters [Time Frame: Up to 24 Weeks]

Number of participants with clinically significant vital sign abnormalities [Time Frame: Up to 24 Weeks]

Number of participants that experience Adverse Events (AEs) and Serious Adverse Events [Time Frame: Up to 24 Weeks]

Number of participants with clinically significant neurological examination abnormalities [Time Frame: Up tp 24 Weeks]

Number of participants who use concomitant medications [Time Frame: Up to 24 Weeks]

Number of participants with clinically significant weight abnormalities [Time Frame: Up to 24 Weeks]

Secondary Outcome(s)

PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible [Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing]

PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax) [Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing]

PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax) [Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing]

PK parameters of nusinersen: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf) [Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing]

Secondary ID(s)

ISIS 396443-CS10

Source(s) of Monetary Support

Please refer to primary and secondary sponsors