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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01780246




Registration number
NCT01780246
Ethics application status
Date submitted
28/01/2013
Date registered
31/01/2013
Date last updated
16/02/2021

Titles & IDs
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
Secondary ID [1] 0 0
ISIS 396443-CS10
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Muscular Atrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - nusinersen

Experimental: nusinersen -


Treatment: Drugs: nusinersen
Administered by intrathecal (IT) injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Timepoint [1] 0 0
Up to 24 Weeks
Primary outcome [2] 0 0
Number of participants with clinically significant neurological examination abnormalities
Timepoint [2] 0 0
Up tp 24 Weeks
Primary outcome [3] 0 0
Number of participants with clinically significant vital sign abnormalities
Timepoint [3] 0 0
Up to 24 Weeks
Primary outcome [4] 0 0
Number of participants with clinically significant physical examination abnormalities
Timepoint [4] 0 0
Up to 24 Weeks
Primary outcome [5] 0 0
Number of participants with clinically significant weight abnormalities
Timepoint [5] 0 0
Up to 24 Weeks
Primary outcome [6] 0 0
Number of participants with clinically significant laboratory parameters
Timepoint [6] 0 0
Up to 24 Weeks
Primary outcome [7] 0 0
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Timepoint [7] 0 0
Up to 24 Weeks
Primary outcome [8] 0 0
Number of participants who use concomitant medications
Timepoint [8] 0 0
Up to 24 Weeks
Secondary outcome [1] 0 0
PK parameters of nusinersen (ISIS 396443): Maximum observed plasma drug concentration (Cmax)
Timepoint [1] 0 0
Plasma at 1, 2, 4 and 6 hours after dosing
Secondary outcome [2] 0 0
PK parameters of nusinersen: Time to reach maximum observed concentration (Tmax)
Timepoint [2] 0 0
Plasma at 1, 2, 4 and 6 hours after dosing
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
Plasma at 1, 2, 4 and 6 hours after dosing
Secondary outcome [4] 0 0
PK parameters of nusinersen (ISIS 396443): Apparent terminal elimination half-life (t1/2), if possible
Timepoint [4] 0 0
Plasma at 1, 2, 4 and 6 hours after dosing

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
2 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/02/2014
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Utah

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to examine the safety and tolerability of nusinersen
(ISIS 396443) administered intrathecally to participants with Spinal Muscular Atrophy (SMA)
who previously participated in ISIS 396443-CS1 (NCT02865109). The secondary objective was to
examine the plasma pharmacokinetics of a single dose of ISIS 396443 administered
intrathecally to participants with SMA who previously participated in ISIS 396443-CS1.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01780246
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries