Overview

This trial is active, not recruiting.

Condition spinal muscular atrophy
Treatment ionis-smnrx
Phase phase 2
Sponsor Ionis Pharmaceuticals, Inc.
Start date May 2013
End date August 2016
Trial size 20 participants
Trial identifier NCT01839656, ISIS 396443-CS3A

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Administered three times by intrathecal injection
ionis-smnrx ISIS 396443
Single intrathecal injection for each dose
(Experimental)
Administered three times by intrathecal injection
ionis-smnrx ISIS 396443
Single intrathecal injection for each dose

Primary Outcomes

Measure
Achievement of motor milestones
time frame: Up to 45 months

Secondary Outcomes

Measure
Plasma Pharmacokinetics
time frame: Up to 45 months
CSF Pharmacokinetics
time frame: Up to 42 months
Event-free survival
time frame: Up to 45 months
Improvement in muscle strength as measured by CHOP-INTEND
time frame: Up to 45 months
Improvement in neuromuscular electrophysiology
time frame: Up to 45 months
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

Eligibility Criteria

Male or female participants up to 210 days old.

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

Additional Information

Official title 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
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Ionis Pharmaceuticals, Inc..