Alport Syndrome, Autosomal Recessive, Alport Syndrome, X-Linked
Conditions
Keywords
Nonsense Mutation, Translational read through
Brief summary
This is a randomized, double-Blind, placebo-controlled study to evaluate the efficacy and safety of exaluren in Alport Syndrome patients with nonsense mutations in COL4A3/4/5 genes. Targeted 24 patients aged 12 and older will be enrolled in the trial. The study will be comprised of the following periods for each participant: * a Screening period of up to 6 weeks (42 days) * a total Treatment Period of exaluren 0.75 mg/kg or placebo administered daily subcutaneously for 32 weeks: Part 1: patients are randomized to either exaluren or placebo for 16 weeks. Part 2: all patients across both randomized arms receive exaluren for 16 additional weeks. * a safety/efficacy Follow-up Period of 4 weeks after the last treatment
Interventions
DRUGExaluren
Exaluren is a synthetic Eukaryotic Ribosome Selective Glycoside (ERSG)
Sponsors
Eloxx Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A confirmed diagnosis of X-linked or autosomal recessive Alport Syndrome with a documented nonsense mutation of COL4A5 in a male or nonsense mutation of COL4A3 or COL4A4 (male or female) * eGFR\>45 ml/min/1.73 m2 * Urinary protein based on two spot urine collections \[urine protein/creatinine ratio (UPCR) ≥ 500 mg/g\] * Stable regimen of ACEi/ARB for at least 12 weeks before Day 1
Exclusion criteria
* History of any organ transplantation * Liver disease characterized by cirrhosis or portal hypertension. Participants with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or a total bilirubin 1.5 times the upper limit of normal (ULN) will be excluded * History of dialysis * Acute kidney injury within 4 weeks before screening * Active dizziness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in the degree of podocyte foot process effacement | Baseline to Week 16 | Measured in kidney biopsies by the change in the Filtration Slit Density (FSD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The percentage change in Urine Protein Creatinine Ratio (UPCR) | Baseline to Week 16 | Calculated from geometric mean of 3 consecutive days of first void urine collection |
Countries
United Kingdom, United States
Outcome results
None listed