A Study to Assess the Safety and Pharmacokinetics of ISIS SMNRx in Infants With Spinal Muscular Atrophy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Isis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01839656
First received: April 22, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Spinal Muscular Atrophy
Drug: ISIS-SMNRx
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Assess the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of ISIS 396443 Delivered Intrathecally to Patients With Infantile-Onset Spinal Muscular Atrophy

Resource links provided by NLM:


Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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)


Other Outcome Measures:
  • 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


Estimated Enrollment: 20
Study Start Date: May 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ISIS-SMNRx Dose level 1
Administered three times by intrathecal injection
Drug: ISIS-SMNRx
Single intrathecal injection for each dose
Experimental: ISIS-SMNRx: Dose level 2
Administered three times by intrathecal injection
Drug: ISIS-SMNRx
Single intrathecal injection for each dose

Detailed Description:

This study will test the safety, tolerability, and pharmacokinetics of multiple doses of ISIS-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.

  Eligibility

Ages Eligible for Study:   up to 210 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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 ClinicalTrials.gov identifier: NCT01839656

Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Florida
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Canada, Ontario
The Hospital for Sick Children (SickKids)
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Isis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Isis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01839656     History of Changes
Other Study ID Numbers: ISIS 396443-CS3A
Study First Received: April 22, 2013
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Isis Pharmaceuticals:
Spinal Muscular Atrophy
SMA
SMN
SMNRx
ISIS-SMNRx
ISIS 396443

Additional relevant MeSH terms:
Atrophy
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

ClinicalTrials.gov processed this record on September 18, 2014