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An Open-label Safety, Tolerability, and Dose-range Finding Study of ISIS SMNRx in Patients With Spinal Muscular Atrophy (SMNRx)

This study has been completed.
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc. Identifier:
First received: December 13, 2011
Last updated: April 23, 2013
Last verified: April 2013
This study will test the safety, tolerability, and pharmacokinetics of escalating doses of ISIS-SMNRx administered into the spinal fluid as a single injection in patients with Spinal Muscular Atrophy.

Condition Intervention Phase
Spinal Muscular Atrophy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Escalating Dose Study to Assess the Safety, Tolerability and Dose-range Finding of a Single Intrathecal Dose of ISIS 396443 in Patients With Spinal Muscular Atrophy

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 4 weeks for cohorts 1 and 2, and 12 weeks for cohorts 3 and 4 ]

Secondary Outcome Measures:
  • Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4 and 20 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 (20 hours after dosing)

Enrollment: 28
Study Start Date: November 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ISIS-SMNRx: Dose level 1 Drug: ISIS-SMNRx
Single intrathecal injection
Experimental: ISIS-SMNRx: Dose level 2 Drug: ISIS-SMNRx
Single intrathecal injection
Experimental: ISIS-SMNRx: Dose level 3 Drug: ISIS-SMNRx
Single intrathecal injection
Experimental: ISIS-SMNRx: Dose level 4 Drug: ISIS-SMNRx
Single intrathecal injection

Detailed Description:
This study will test the safety, tolerability, and pharmacokinetics of escalating doses of ISIS-SMNRx administered as a single intrathecal injection. Four dose levels will be evaluated sequentially. Each dose level will be studied in a cohort of 6 or 10 patients, where all patients will receive active drug.

Ages Eligible for Study:   2 Years to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Documented SMN1 homozygous gene deletion
  • Clinical signs attributable to Spinal Muscular Atrophy
  • Males and females 2 to 14 years of age at time of screening
  • 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:

  • Respiratory insufficiency defined by the need for invasive or non-invasive ventilation during a 24 hour period
  • Presence of a gastric feeding tube
  • Previous scoliosis surgery or scoliosis surgery planned during the duration of the study that would interfere with the LP injection procedure
  • Hospitalization for surgery or pulmonary event within the last 2 months or planned during the study
  • Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy
  • History of brain or spinal cord disease that would interfere with lumbar puncture procedures or CSF circulation
  • Presence of an implanted shunt for the draining of CSF or an implanted CNS catheter
  • History of bacterial meningitis
  • 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
  • Ongoing medical condition that would interfere with the conduct and assessments of the study. Examples are medical disability (e.g. wasting or cachexia, severe anemia, etc.) that would interfere with the assessment of safety or would compromised the ability of the patient to undergo study procedures
  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: NCT01494701

United States, Massachusetts
Children's Hospital Boston
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: NCT01494701     History of Changes
Other Study ID Numbers: ISIS 396443 - CS1
Study First Received: December 13, 2011
Last Updated: April 23, 2013

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

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Cord Diseases
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases processed this record on March 24, 2017