Overview

This trial is active, not recruiting.

Condition spinal muscular atrophy
Treatments nusinersen, sham procedure
Phase phase 2
Sponsor Biogen
Collaborator Ionis Pharmaceuticals, Inc.
Start date June 2015
End date January 2018
Trial size 21 participants
Trial identifier NCT02462759, 2014-003657-33, 232SM202

Summary

The primary objective of Part 1 of this study is to assess the safety and tolerability of Nusinersen in participants with SMA who are not eligible to participate in the clinical studies ISIS 396443-CS3B (NCT02193074) or ISIS 396443-CS4 (NCT02292537). The secondary objective of Part 1 of this study is to examine the pharmacokinetics (PK) of Nusinersen in participants with SMA. The primary objective of Part 2 of this study is to assess the long-term safety and tolerability of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments. The secondary objective of Part 2 of this study is to examine the PK of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Administered by intrathecal injection.
nusinersen BIIB058
Administered by intrathecal injection.
(Sham Comparator)
Small needle prick on the lower back at the location where the IT injection is normally made.
sham procedure
Small needle prick on the lower back at the location where the IT injection is normally made.

Primary Outcomes

Measure
Number of participants with adverse events and serious adverse events
time frame: Up to 44 months
Change from Baseline in clinical laboratory parameters
time frame: Baseline and 14 months (Part 1) and 30 months (Part 2)
Change from Baseline in electrocardiograms (ECGs)
time frame: Baseline and 14 months (Part 1) and 30 months (Part 2)
Change from Baseline in vital signs
time frame: Baseline and 14 months (Part 1) and 30 months (Part 2)
Change from Baseline in neurological examination outcomes
time frame: Baseline and 14 months (Part 1) and 30 months (Part 2)

Secondary Outcomes

Measure
Nusinersen plasma concentration
time frame: Up to Day 897
Nusinersen cerebrospinal fluid (CSF) concentration
time frame: Up to Day 897

Eligibility Criteria

Male or female participants of any age.

Key Inclusion Criteria: - Genetic documentation of 5q SMA homozygous gene deletion, mutation, or compound heterozygote. - Onset of clinical signs and symptoms consistent with SMA at ≤6 months of age and have documentation of 3 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at ≤6 months of age, >7 months of age (211 days) at screening, and have documentation of 2 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at >6 months of age, are ≤18 months of age at screening, and have documentation of 2 or 3 SMN2 copies. - Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures. - Medical care, such as routine immunizations meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA, in the opinion of the Investigator. - Participants with 2 SMN2 copies must reside within approximately 9 hours' ground-travel distance from a participating study site for the duration of the study. Key Exclusion Criteria: - Meets additional study related criteria. - Any previous exposure to ISIS 396443; previous dosing in this study or previous studies with ISIS 396443. - Signs or symptoms of SMA present at birth or within the first week after birth. - Ventilation for ≥16 hours per day continuously for >21 days at screening. - Permanent tracheostomy, implanted shunt for CSF drainage, or implanted central nervous system (CNS) catheter at screening. - History of brain or spinal cord disease that would interfere with the LP procedure, CSF circulation, or safety assessments. - Hospitalization for surgery (e.g., scoliosis surgery), pulmonary event, or nutritional support within 2 months prior to screening, or hospitalization for surgery planned during the study. - Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Investigator. - Treatment with an investigational drug for SMA (e.g., albuterol/salbutamol, riluzole, carnitine, sodium phenylbutyrate, valproate, hydroxyurea), biological agent, or device within 30 days prior to screening. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation. For Part 2 only: To be eligible to participate in Part 2 of this study, participants must meet the following eligibility criteria at the time of consent to participate in Part 2: Participation in Part 1 and completion of the End of Part 1 Evaluation assessments. Ability of parent(s) or legal guardian(s) to understand the purpose and risks of the study and to provide signed and dated informed consent on the Part 2 informed consent form (ICF) and authorization to use confidential health information in accordance with national and local participant privacy regulations. Able to complete all study procedures, measurements, and visits, and parent or legal guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the Investigator. Participants will be excluded from the Part 2 if they meet the following exclusion criterion at the time of consent into Part 2 of the study: Any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in Part 2. The Investigator must reassess the subject's medical fitness for participation and consider any diseases that would preclude treatment. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Additional Information

Official title A Phase 2, Randomized, Double-blind, Sham-procedure Controlled Study to Assess the Safety and Tolerability and Explore the Efficacy of ISIS 396443 (BIIB058) Administered Intrathecally in Subjects With Spinal Muscular Atrophy Who Are Not Eligible to Participate in the Clinical Studies ISIS 396443-CS3B or ISIS 396443-CS4
Description Part 2 is an Open Label extension phase.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Biogen.