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An Open-label Safety and Tolerability Study of IONIS SMNRx in Patients With Spinal Muscular Atrophy Who Previously Participated in IONIS SMNRx-CS2 or IONIS SMNRx-CS10

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc. Identifier:
First received: January 30, 2014
Last updated: December 31, 2015
Last verified: December 2015
This study will test the safety and tolerability of multiple doses of IONIS-SMNRx administered into the spinal fluid in patients with Spinal Muscular Atrophy, who previously participated in IONIS 396443-CS2 or IONIS 396443-CS10.

Condition Intervention Phase
Spinal Muscular Atrophy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Ionis Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 24 months ]

Secondary Outcome Measures:
  • 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)

Estimated Enrollment: 52
Study Start Date: January 2014
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IONIS-SMNRx
Dose Level 1
Multiple doses by intrathecal injection
Other Name: ISIS 396443

Detailed Description:
This study will test the safety, tolerability, and pharmacokinetics of multiple doses of IONIS-SMNRx administered as an intrathecal injection. Multiple doses will be studied in patients with Spinal Muscular Atrophy, who previously participated in IONIS 396443-CS2 or IONIS 396443-CS10, and all patients will receive active drug.

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

Inclusion Criteria:

  • Clinical signs attributable to Spinal Muscular Atrophy
  • Satisfactory completion of dosing and all study visits in IONIS 396443-CS2 or IONIS 396443 CS10 with an acceptable safety profile, per Investigator judgement.
  • Able to complete all study procedures, measurements and visits and parent/patient 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

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 subject participating in or completing the study.
  • Dosing in IONIS 396443-CS2 or IONIS 396443-CS10 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02052791

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
Ionis Pharmaceuticals, Inc.
  More Information

Responsible Party: Ionis Pharmaceuticals, Inc. Identifier: NCT02052791     History of Changes
Other Study ID Numbers: ISIS 396443-CS12 
Study First Received: January 30, 2014
Last Updated: December 31, 2015

Keywords provided by Ionis Pharmaceuticals, Inc.:
Spinal Muscular Atrophy
ISIS 396443

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
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 processed this record on February 20, 2017