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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Isis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01494701

First received: December 13, 2011

Last updated: April 23, 2013

Last verified: April 2013

History of Changes

Tracking Information
First Received Date ^ICMJE	December 13, 2011
Last Updated Date	April 23, 2013
Start Date ^ICMJE	November 2011
Primary Completion Date	January 2013 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: May 7, 2012)	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 ] [ Designated as safety issue: Yes ]
Original Primary Outcome Measures ^ICMJE (submitted: December 15, 2011)	The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 4 weeks ] [ Designated as safety issue: Yes ]
Change History	Complete list of historical versions of study NCT01494701 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: December 15, 2011)	Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4 and 20 hours after dosing ] [ Designated as safety issue: No ] 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)
Original Secondary Outcome Measures ^ICMJE	Same as current
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	An Open-label Safety, Tolerability, and Dose-range Finding Study of ISIS SMNRx in Patients With Spinal Muscular Atrophy
Official Title ^ICMJE	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
Brief Summary	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.
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.
Study Type ^ICMJE	Interventional
Study Phase	Phase 1
Study Design ^ICMJE	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Condition ^ICMJE	Spinal Muscular Atrophy
Intervention ^ICMJE	Drug: ISIS-SMNRx Single intrathecal injection
Study Arm (s)	Experimental: ISIS-SMNRx: Dose level 1 Intervention: Drug: ISIS-SMNRx Experimental: ISIS-SMNRx: Dose level 2 Intervention: Drug: ISIS-SMNRx Experimental: ISIS-SMNRx: Dose level 3 Intervention: Drug: ISIS-SMNRx Experimental: ISIS-SMNRx: Dose level 4 Intervention: Drug: ISIS-SMNRx
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	28
Completion Date	January 2013
Primary Completion Date	January 2013 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	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
Gender	Both
Ages	2 Years to 14 Years
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	United States

Administrative Information
NCT Number ^ICMJE	NCT01494701
Other Study ID Numbers ^ICMJE	ISIS 396443 - CS1
Has Data Monitoring Committee	Yes
Responsible Party	Isis Pharmaceuticals
Study Sponsor ^ICMJE	Isis Pharmaceuticals
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Isis Pharmaceuticals
Verification Date	April 2013
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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