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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)

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ClinicalTrials.gov Identifier: NCT02052791
Recruitment Status : Completed
First Posted : February 3, 2014
Last Update Posted : March 24, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE January 30, 2014
First Posted Date  ICMJE February 3, 2014
Last Update Posted Date March 24, 2017
Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2017)
  • Number of participants that experience Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Up to 24 Months ]
  • Number of participants with clinically significant neurological examination 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 with clinically significant physical examination abnormalities [ 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 laboratory parameters [ Time Frame: Up to 24 Months ]
  • Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters [ Time Frame: Up to Day 176 ]
  • Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [ Time Frame: Up to 24 Months ]
  • Change from Baseline in concomitant medications [ Time Frame: Up to 24 Months ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2014)
The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 9 months ]
Change History Complete list of historical versions of study NCT02052791 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2017)
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2014)
Plasma Pharmacokinetics [ Time Frame: Plasma at 1, 2, 4 and 6 hours after dosing ]
  • The maximal observed plasma drug concentration (Cmax)
  • The time to reach Cmax in plasma (Tmax)
  • The area under the plasma concentrations time curve from the time of the intrathecal dose to the last collected sample (6 hours after dosing)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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-CS2 (NCT01703988) or ISIS 396443-CS10 (NCT01780246). The secondary objective is to examine the plasma and cerebrospinal fluid (CSF) pharmacokinetic(s) (PK) of nusinersen administered intrathecally to participants with SMA who previously participated in ISIS 396443-CS2 or ISIS 396443-CS10.
Detailed Description

This study was conducted and the protocol was registered by Ionis Pharmaceuticals, Inc.

In August 2016, sponsorship of the trial was transferred to Biogen.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Spinal Muscular Atrophy
Intervention  ICMJE Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx
Study Arms  ICMJE Experimental: nusinersen
Intervention: Drug: nusinersen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 22, 2017)
47
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2014)
52
Actual Study Completion Date  ICMJE January 2017
Actual Primary Completion Date January 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02052791
Other Study ID Numbers  ICMJE ISIS 396443-CS12
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP