An Open-label Safety, Tolerability and Dose-range Finding Study of Multiple Doses of ISIS SMNRx in Patient With Spinal Muscular Atrophy (SMNRx - CS2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01703988
First received: October 8, 2012
Last updated: April 4, 2014
Last verified: April 2014

October 8, 2012
April 4, 2014
October 2012
December 2014   (final data collection date for primary outcome measure)
The number of participants with adverse events [ Time Frame: Patricipants will be followed for the duration of the study; an expected 36 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01703988 on ClinicalTrials.gov Archive Site
Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4, 6 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)
Same as current
CSF Pharmacokinetics (See clarification.) [ Time Frame: CSF at Day 1, Day 29, and Day 85 ] [ Designated as safety issue: No ]
- The observed CSF drug concentration
Same as current
 
An Open-label Safety, Tolerability and Dose-range Finding Study of Multiple Doses of ISIS SMNRx in Patient With Spinal Muscular Atrophy
An Open-Label, Dose Escalation Study to Assess the Safety, Tolerability and Dose-Range Finding of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Spinal Muscular Atrophy

This study will test the safety, tolerability, and pharmacokinetics of escalating doses of ISIS-SMNRx administered into the spinal fluid either two or three times over the duration of the trial, in patients with Spinal Muscular Atrophy.

This study will test the safety, tolerability, and pharmacokinetics of escalating doses of ISIS-SMNRx administered multiple times over the duration of the trial, as intrathecal injections. Four dose levels will be evaluated sequentially. Each dose level will be studied in a cohort of 8 patients, where all patients will receive active drug.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Spinal Muscular Atrophy
Drug: ISIS-SMNRx
Single intrathecal injection for each dose
  • Experimental: ISIS-SMNRx Dose level 1
    Administered three times by intrathecal injection
    Intervention: Drug: ISIS-SMNRx
  • Experimental: ISIS-SMNRx: Dose level 2
    Administered three times by intrathecal injection
    Intervention: Drug: ISIS-SMNRx
  • Experimental: ISIS-SMNRx: Dose level 3
    Administered two times by intrathecal injection
    Intervention: Drug: ISIS-SMNRx
  • Experimental: Experimental: ISIS-SMNRx: Dose level 4
    Administered three times by intrathecal injection
    Intervention: Drug: ISIS-SMNRx
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
32
January 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Genetic documentation of 5q SMA (homozygous gene deletion or mutation)
  • Clinical signs attributable to Spinal Muscular Atrophy
  • Males and females 2 to 15 years of age
  • 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 medical necessity for invasive or non-invasive ventilation during a 24 hour period
  • Medical necessity for a gastric feeding tube, where the majority of feeds are given by this route, as assessed by the Site Investigator
  • Previous scoliosis surgery that would interfere with the lumbar puncture injection procedure
  • 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 at any time during the screening period
  • History of brain or spinal cord disease that would interfere with lumbar puncture procedures or CSF circulation
  • Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
  • History of bacterial meningitis
  • Dosing with ISIS 396443 in clinical study ISIS 396443-CS1 Cohorts 2, 3, or 4
  • Dosing with ISIS 396443 in clinical study ISIS 396443 - CS10
  • 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 3-months of screening. 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 compromise the ability of the patient to undergo study procedures.
Both
2 Years to 15 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01703988
ISIS 396443 - CS2
Yes
Isis Pharmaceuticals
Isis Pharmaceuticals
Not Provided
Not Provided
Isis Pharmaceuticals
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP