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)

February 12, 2021 updated by: Biogen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Texas
      • Dallas, Texas, United States, 75207
        • UT Southwestern Medical Center - Children's Medical Center Dallas
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 15 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: nusinersen
Drug: nusinersen
Administered by intrathecal (IT) injection
Other Names:
  • ISIS 396443
  • BIIB058
  • IONIS-SMN Rx
  • Sprinraza

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants that experience Adverse Events (AEs) and Serious Adverse Events
Time Frame: Up to 24 Weeks
Up to 24 Weeks
Number of participants with clinically significant neurological examination abnormalities
Time Frame: Up tp 24 Weeks
Up tp 24 Weeks
Number of participants with clinically significant vital sign abnormalities
Time Frame: Up to 24 Weeks
Up to 24 Weeks
Number of participants with clinically significant physical examination abnormalities
Time Frame: Up to 24 Weeks
Up to 24 Weeks
Number of participants with clinically significant weight abnormalities
Time Frame: Up to 24 Weeks
Up to 24 Weeks
Number of participants with clinically significant laboratory parameters
Time Frame: Up to 24 Weeks
Up to 24 Weeks
Number of participants with clinically significant electrocardiograms (ECGs) abnormalities
Time Frame: Up to 24 Weeks
Up to 24 Weeks
Number of participants who use concomitant medications
Time Frame: Up to 24 Weeks
Up to 24 Weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 31, 2013

Primary Completion (ACTUAL)

February 28, 2014

Study Completion (ACTUAL)

February 28, 2014

Study Registration Dates

First Submitted

January 28, 2013

First Submitted That Met QC Criteria

January 28, 2013

First Posted (ESTIMATE)

January 31, 2013

Study Record Updates

Last Update Posted (ACTUAL)

February 16, 2021

Last Update Submitted That Met QC Criteria

February 12, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISIS 396443-CS10

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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