Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients with Alexander Disease

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2020-000976-40-GB
• Date of registration: 28/07/2020
• Prospective Registration: Yes
• Primary sponsor: Ionis Pharmaceuticals, Inc
• Public title: Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients with Alexander Disease
• Scientific title: A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients with Alexander Disease
• Target sample size: 42
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000976-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Canada, Israel, Italy, Japan, Netherlands, United Kingdom, United States

Contacts

• Name: Ionis Clinical Trial Information
• Affiliation: Ionis Pharmaceuticals, Inc.

• Name: Ionis Clinical Trial Information
• Affiliation: Ionis Pharmaceuticals, Inc.

Key inclusion & exclusion 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
4.Able and willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits
5.Patients < 18 years old at Screening must have a trial partner (parent, caregiver or other)

Are the trial subjects under 18? yes
Number of subjects for this age range: 31
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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
6.History of gene therapy or cell transplantation or any other experimental brain surgery
7.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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alexander Disease
MedDRA version: 22.1 Level: PT Classification code 10083059 Term: Alexander disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: ION373
Product Code: ION373
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ION373
CAS Number: 2305355-56-8
Current Sponsor code: ION373
Other descriptive name: 2'-O-(2-METHOXYETHYL)-D-RIBOSE ANTISENSE OLIGONUCLEOTIDE TARGETING GLIAL FIBRILLARY ACIDIC PROTEIN MESSENGER RIBONUCLEIC ACID
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intrathecal use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121

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

Main Objective: To evaluate the efficacy of ION373 in improving or stabilizing gross motor function 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.

Secondary Outcome(s)

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

Secondary ID(s)

ION373-CS1

Source(s) of Monetary Support

Ionis Pharmaceuticals, Inc.