Alexander Disease MedDRA version: 22.1 Level: PT Classification code 10083059 Term: Alexander disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Ionis Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Clinical phenotype and brain imaging consistent with a diagnosis of Alexander disease 2.Documented genetic mutation in the GFAP gene 3.Aged = 2 to 65 years old at the time of informed consent (eligibility for main study) or aged =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Clinically significant abnormalities in medical history or physical examination 2.Platelet count or any other clinically significant laboratory abnormalities that would render a patient unsuitable for inclusion 3.Any contraindication or unwillingness to undergo MRI 4.Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer; concurrent participation in any other clinical study (including observational and non-interventional studies) 5.Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received or history of hypersensitivity to ION373 or its excipients or history of hypersensitivity to any ASO. This exclusion does not apply to vaccines (both mRNA and viral vector vaccines). 6.History of gene therapy or cell transplantation or any other experimental brain surgery 7.Current obstructive hydrocephalus 8.Presence of a functional ventriculoperitoneal shunt for the drainage of CSF or an implanted CNS catheter 9.known brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment. 10.Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study 11.Have any other conditions, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study 12. History of gene therapy or cell transplantation or any other experimental brain surgery 13. Current obstructive hydrocephalus 14. Presence of a functional ventriculoperitoneal shunt for the drainage of CSF or an implanted CNS catheter 15. Any condition that increases risk of meningitis unless patient is receiving appropriate prophylactic treatment 16. Known brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment, including tumors or abnormalities by MRI or computed tomography, subarachnoid hemorrhage, spinal stenosis or curvature, Chiari malformation, syringomyelia, tethered spinal cord syndrome and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome 17. History of severe post-LP headache and/or blood patch 18. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study 19. Recent history of, or current drug or alcohol abuse 20. Antiplatelet or anticoagulant therapy within the 14 days prior to Screening or anticipated use during the study, including but not limited to aspirin (unless = 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban 21. Have any other conditions, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study, such as the presence of a chronic condition which places the patient at higher risk from procedural sedation or anesthesia if this is deemed necessary by the Investigator for completion study procedures including the lumbar punctures and/or brain MRI scans
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ION373 in improving or stabilizing gross motor function in patients with Alexander disease ;Secondary Objective: To further evaluate the efficacy of ION373 in improving or stabilizing disease manifestations across the full range of affected domains (gross and fine motor, communication, swallowing, autonomic and/or other gastrointestinal functions, nutritional/growth status) in patients with Alexander disease;Primary end point(s): Percent change from Baseline to Week 61 in the 10MWT in patients who are in Stratum 1.;Timepoint(s) of evaluation of this end point: baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: Change from Baseline to Week 61 or value at Week 61 for the following: • Patients’ self-identified most bothersome symptom (based on a Likert scale for change; all patients) • PedsQL Generic Core Scales (all patients) • Patient Global Impression of Severity (PGIS; all patients) • Patient Global Impression of Change (PGIC; all patients) • Clinical Global Impression of Change (CGIC; all patients) Other Secondary Endpoints: Change from Baseline to Week 61 or value at Week 61 for the following: • Gross Motor Function Measure-88, Dimensions C, D and E (GMFM-88, Dimensions C-E; patients < 5 years old at Screening) or 10MWT (patients = 5 years old at Screening) • 9-Hole Peg Test (9HPT; patients = 8 years old at Screening) • Vineland-3 Motor Skills Domain (patients < 8 years old at Screening) • PedsQL Gastrointestinal Symptoms Scales (all patients) • Vineland-3 Adaptive Behavior Composite (ABC) Score (patients < 18 years old at Screening) • Composite Autonomic Symptom Score 31 (COMPASS-31; patients = 18 years old at Screening) • CSF GFAP levels (all patients) • Clinical Global Impression of Severity (CGIS; all patients) • Alexander Disease Patient Domain Impression of Severity (AxD-PDIS; all patients) •Alexander Disease Patient Domain Impression of Change (AxD-PDIC; all patients) • Body weight percentile (for patients < 18 years old at Screening) or body weight (for patients = 18 years old at Screening;Timepoint(s) of evaluation of this end point: baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121 | — |
Countries
Canada, Israel, Italy, Japan, Netherlands, United Kingdom, United States
Contacts
Public ContactIonis Clinical Trial Information
Ionis Pharmaceuticals, Inc.
Outcome results
None listed