Trial record 1 of 1 for:    NCT01839656
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A Study to Assess the Efficacy, Safety and Pharmacokinetics of IONIS SMNRx in Infants With Spinal Muscular Atrophy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01839656
First received: April 22, 2013
Last updated: May 6, 2016
Last verified: May 2016

April 22, 2013
May 6, 2016
May 2013
August 2016   (final data collection date for primary outcome measure)
Achievement of motor milestones [ Time Frame: Up to 45 months ] [ Designated as safety issue: No ]
As evaluated by Module 2 of the Hammersmith Infant Neurological Examination
The number of participants with adverse events [ Time Frame: Patricipants will be followed for the duration of the study; an expected 52 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01839656 on ClinicalTrials.gov Archive Site
  • Plasma Pharmacokinetics [ Time Frame: Up to 45 months ] [ Designated as safety issue: No ]
    The observed plasma drug concentration
  • CSF Pharmacokinetics [ Time Frame: Up to 42 months ] [ Designated as safety issue: No ]
    The observed CSF drug concentration
  • Event-free survival [ Time Frame: Up to 45 months ] [ Designated as safety issue: No ]
    As determined by the proportion of subjects who are alive and do not require permanent ventilator support
  • Improvement in muscle strength as measured by CHOP-INTEND [ Time Frame: Up to 45 months ] [ Designated as safety issue: No ]
  • Improvement in neuromuscular electrophysiology [ Time Frame: Up to 45 months ] [ Designated as safety issue: No ]
    As measured by CMAP
  • Safety and tolerability as assessed by adverse events, neurological examinations, vital signs, physical examination and weight, clinical laboratory tests, ECGs, and use of concomitant medications [ Time Frame: Up to 45 months ] [ Designated as safety issue: Yes ]
Plasma Pharmacokinetics (See clarification.) [ Time Frame: Plasma at 1, 2, 4 and 24 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)
Not Provided
CSF Pharmacokinetics (See clarification.) [ Time Frame: CSF at Day 1, Day 15, and Day 85 ] [ Designated as safety issue: No ]
- The observed CSF drug concentration
 
A Study to Assess the Efficacy, Safety and Pharmacokinetics of IONIS SMNRx in Infants With Spinal Muscular Atrophy
A Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Infantile-Onset Spinal Muscular Atrophy
This study will test the efficacy, safety, tolerability, and pharmacokinetics of multiple doses of IONIS-SMNRx administered into the spinal fluid three times over the duration of the trial, in patients with Infantile-Onset Spinal Muscular Atrophy.
This study will test the efficacy, safety, tolerability, and pharmacokinetics of multiple doses of IONIS-SMNRx administered into the spinal fluid three times over the duration of the trial, in patients with Infantile-Onset Spinal Muscular Atrophy. Two dose levels will be evaluated sequentially. The lowest dose level will be studied in a cohort of 4 patients, and the highest dose level will be studied in a cohort of 4-16 patients. All patients will receive active drug.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Spinal Muscular Atrophy
Drug: IONIS-SMNRx
Single intrathecal injection for each dose
Other Name: ISIS 396443
  • Experimental: IONIS-SMNRx Dose level 1
    Administered three times by intrathecal injection
    Intervention: Drug: IONIS-SMNRx
  • Experimental: IONIS-SMNRx: Dose level 2
    Administered three times by intrathecal injection
    Intervention: Drug: IONIS-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
20
November 2016
August 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Genetic documentation of 5q SMA (homozygous gene deletion or mutation)
  • Onset of clinical signs and symptoms consistent with SMA at ≥ 21 days and <6 months (180 days) of age
  • At study entry, receiving adequate nutrition and hydration (with or without gastrostomy), in the opinion of the Site Investigator
  • Body weight >5th percentile for age using CDC guidelines
  • Medical care meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA (Wang et al. 2007), in the opinion of the Site Investigator
  • Gestational age of 35 to 42 weeks and gestation body weight ≥2 kg
  • Reside within approximately 9 hours ground-travel distance from a participating study center for the duration of the study. Residence >2 hours ground-travel distance from a study center must obtain clearance from the Site Investigator and the study Medical Monitor
  • Able to complete all study procedures, measurements and visits and parent or guardian/subject has adequately supportive psychosocial circumstances, in the opinion of the Site Investigator

Exclusion Criteria:

  • Hypoxemia (O2 saturation awake <96% or O2 saturation asleep <96%, without ventilation support)
  • 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 the LP procedures, CSF circulation, or safety assessments
  • Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
  • History of bacterial meningitis
  • Clinically significant abnormalities in hematology or clinical chemistry parameters, as assessed by the Site Investigator, at screening that would render the subject unsuitable for inclusion
  • Treatment with another investigational drug (e.g., albuterol, riluzole, carnitine, creatine, sodium phenylbutyrate, salbutamol, valproate, hydroxyurea etc), biological agent, or device within 90 days prior to enrollment or anytime during the study. Any history of gene therapy or cell transplantation
  • The subject's parent(s) or legal guardian(s) is unable to understand the nature, scope, and possible consequences of the study, or does not agree to comply with the protocol defined schedule of assessments
  • Ongoing medical condition that according to the Site Investigator would interfere with the conduct and assessments of the study. Examples are medical disability other than SMA that would interfere with the assessment of safety or would compromise the ability of the subject to undergo study procedures
Both
up to 210 Days   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01839656
ISIS 396443-CS3A
Yes
Not Provided
Not Provided
Ionis Pharmaceuticals, Inc.
Ionis Pharmaceuticals, Inc.
Not Provided
Not Provided
Ionis Pharmaceuticals, Inc.
May 2016

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