An Open-label Safety and Tolerability Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) Who Previously Participated in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246)

• Register: ClinicalTrials.gov
• Last refreshed on: 22 February 2021
• Main ID: NCT02052791
• Date of registration: 30/01/2014
• 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 (SMA) Who Previously Participated in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246)
• Scientific title: An Open-label Study to Assess the Safety and Tolerability of ISIS 396443 in Patients With Spinal Muscular Atrophy Who Previously Participated in 396443-CS2 or 396443-CS10
• Date of first enrolment: January 31, 2014
• Target sample size: 47
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02052791
• 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

Contacts

• Name: Medical Director
• Affiliation: Biogen

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-CS2
(NCT01703988) or ISIS 396443 CS10 (NCT01780246) 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 subject unsuitable for enrollment, or could interfere with
the participant participating in or completing the study.

- Dosing in ISIS 396443-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246) within 180
days (6 months) of screening, or longer ago than 396 days (13 months) from screening

- 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

- Clinically significant abnormalities in hematology or clinical chemistry parameters

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

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



Age minimum: N/A
Age maximum: N/A
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 electrocardiograms (ECGs) abnormalities [Time Frame: Up to 24 Months]

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

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

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

Number of participants with clinically significant physical examination abnormalities [Time Frame: Up to 24 Months]

Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters [Time Frame: Up to Day 176]

Change from Baseline in concomitant medications [Time Frame: Up to 24 Months]

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

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

Secondary Outcome(s)

PK parameters of nusinersen in CSF levels: Area under the plasma concentrations time curve from the time of the intrathecal (IT) dose to the last collected sample (AUCinf) [Time Frame: Pre-Dose Day 176, Day 358 and Day 540]

PK parameters of nusinersen (ISIS 396443) in CSF levels: Maximum observed plasma drug concentration (Cmax) [Time Frame: Pre-dose Day 176, Day 358 and Day 540]

PK parameters of nusinersen in CSF levels: Time to reach maximum observed concentration (Tmax) [Time Frame: Pre-Dose Day 176, Day 358 and Day 540]

Secondary ID(s)

ISIS 396443-CS12

Source(s) of Monetary Support

Please refer to primary and secondary sponsors