A Study of ELX-02 in Patients With Alport Syndrome

Study Overview
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Brief Summary
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This is a Phase 2 open label pilot study to evaluate the safety and efficacy of subcutaneously administered ELX-02 in patients with X-linked or autosomal recessive Alport Syndrome with Col4A5 and Col4A3/4 nonsense mutation. In total, up to 8 participants, with a minimum of 3 adults, 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 8 weeks (60 days) a safety/efficacy Follow-up Period of 12 weeks (90 days) after the last treatment The Treatment Period will be a treatment of ELX-02 0.75 mg/kg SC QD for 8 weeks.

Official Title
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A Phase 2 Open Label Pilot Study to Evaluate the Safety and Efficacy of Subcutaneously Administered ELX-02 in Patients With Alport Syndrome With Col4A5 and Col4A3/4 Nonsense Mutation

Conditions
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Alport Syndrome

Intervention / Treatment
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* Drug: ELX-02


Participation Criteria
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Eligibility Criteria
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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) The nonsense mutation should be UAG or UGA eGFR>60 ml/min/1.73 m2 (based on CKD-EPI for ages ≥18 and Schwartz formula for participants <18) Urinary protein based on two spot urine collections [urine protein/creatinine ratio (UPCR) ≥ 500 mg/g] Stable regimen of ACEi/ARB for at least 4 weeks before screening (unless there is a contraindication) Exclusion Criteria: History of any organ transplantation Mutation consistent with autosomal dominant Alport Syndrome Liver disease characterized by cirrhosis or portal hypertension. Participants with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or a total bilirubin 3.0 times the upper limit of normal (ULN) will be excluded History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) ≤ 40% History of dialysis

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label study drug treatment<br> | Drug: ELX-02<br>* ELX-02 is a small molecule, new chemical entity being developed for the treatment of genetic diseases caused by nonsense mutations. ELX-02 is a eukaryotic ribosomal selective glycoside (ERSG).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and characteristics of adverse events |  | From the time of first dosing through the end of the follow-up period, a total of 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in proteinuria |  | From screening assessment to end of study treatment and end of follow up period, two and five months respectively | 
| Change in Col IV expression in renal biopsy |  | From biopsy collected at screening to the biopsy collected at the end of study treatment, a two months interval | 
| Change in hematuria |  | From screening assessment to end of study treatment and end of follow up period, two and five months respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aminoglycoside, Nonsense Mutation, Translational read through