EXACT Study: A Blinded Study in Patients With Alport Syndrome to Evaluate Exaluren Efficacy and Safety

A Randomized, Double-Blind, Placebo-Controlled, Delayed-Start Study to Evaluate the Efficacy and Safety of Exaluren in Alport Syndrome Patients With Nonsense Mutations in COL4A3/4/5 Genes

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

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