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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Drug: nusinersen Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : January 2014
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Nusinersen

Arms and Interventions
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Arm Intervention/treatment
Experimental: nusinersen Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • Spinraza
  • BIIB058
  • IONIS SMN Rx
  • ISIS SMNRx


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants that experience Adverse Events (AEs) and Serious Adverse Events [ Time Frame: Up to 24 Months ]
  2. Number of participants with clinically significant neurological examination abnormalities [ Time Frame: Up to 24 Months ]
  3. Number of participants with clinically significant vital sign abnormalities [ Time Frame: Up to 24 Months ]
  4. Number of participants with clinically significant physical examination abnormalities [ Time Frame: Up to 24 Months ]
  5. Number of participants with clinically significant weight abnormalities [ Time Frame: Up to 24 Months ]
  6. Number of participants with clinically significant laboratory parameters [ Time Frame: Up to 24 Months ]
  7. Number or participants with clinically significant cerbrospinal fluid (CSF) laboratory parameters [ Time Frame: Up to Day 176 ]
  8. Number of participants with clinically significant electrocardiograms (ECGs) abnormalities [ Time Frame: Up to 24 Months ]
  9. Change from Baseline in concomitant medications [ Time Frame: Up to 24 Months ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02052791


Locations
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United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
UT Southwestern Medical Center - Children's Medical Center Dallas
Dallas, Texas, United States, 75207
United States, Utah
University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02052791    
Other Study ID Numbers: ISIS 396443-CS12
First Posted: February 3, 2014    Key Record Dates
Last Update Posted: March 24, 2017
Last Verified: March 2017
Keywords provided by Biogen:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
 ISIS 396443
IONIS-SMNRx
IONIS-SMN Rx
Spinraza
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
 Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases