A Study to Assess the Efficacy, Safety and Pharmacokinetics of IONIS SMNRx in Infants With Spinal Muscular Atrophy
- Conditions
- Spinal Muscular Atrophy (SMA)Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2017-000621-12-Outside-EU/EEA
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 20
1. Signed informed consent of parent(s) or guardian(s)
2. Genetic documentation of 5q SMA homozygous gene deletion or mutation
3. Onset of clinical signs and symptoms consistent with SMA at = 21 days and = 6 months (180 days) of age
4. Males and females between = 21 days and = 7 months (210 days) of age at Screening
5. At study entry, receiving adequate nutrition and hydration (with or without gastrostomy), in the opinion of the Site Investigator
6. Body weight > 5th percentile for age using CDC guidelines
7. 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
8. Gestational age of 35 to 42 weeks and gestation body weight = 2 kg
9. 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
10. 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Hypoxemia (O2 saturation awake < 96% or O2 saturation asleep < 96%, without ventilation support)
2. Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period
3. History of brain or spinal cord disease that would interfere with the LP procedures, CSF circulation, or safety assessments
4. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
5. History of bacterial meningitis
6. 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
7. 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
8. 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
9. 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To examine the clinical efficacy of multiple doses of ISIS 396443 administered intrathecally to patients with Infantile-Onset SMA.;Secondary Objective: To examine the safety and tolerability of multiple doses of ISIS 396443 administered intrathecally to patients with infantile-onset SMA.<br>To examine the cerebral spinal fluid (CSF) and plasma PK of multiple doses of ISIS 396443 administered intrathecally to patients with infantile-onset SMA.;Primary end point(s): -Achieve improvement of motor milestones ;Timepoint(s) of evaluation of this end point: Up to 45 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -Plasma and CSF Pharmacokinetics <br>-Event-free survival <br>-Improvement in muscle strength as measured by CHOP-INTEND <br>-Improvement in neuromuscular electrophysiology <br>-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<br>;Timepoint(s) of evaluation of this end point: Up to 45 months