Alport syndrome Genetic Diseases Other specified congenital malformation syndromes, not elsewhere classified
Conditions
Interventions
Patients will receive a treatment of ELX-02 0.75 mg/kg subcutaneously administered once a day for 8 weeks. After their last treatment, patients will be followed up for 12 weeks.
Sponsors
Eloxx Pharmaceuticals (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or their parent/legal guardian) has been informed of all pertinent aspects of the trial 2. Understands, and is willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures 3. Male and female participants 4. Aged between 6 and 30 years 5. 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) 6. The nonsense mutation should be UAG or UGA 7. eGFR >60 ml/min/1.73 m² (based on Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] for ages =18 years and Schwartz formula for participants <18 years) 8. Urinary protein based on two spot urine collections [urine protein/creatinine ratio (UPCR) =500 mg/g] 9. Stable regimen of ACEi/ARB for 4 weeks before screening (unless there is a contraindication) 10. Must be willing to abstain from strenuous exercise during the 48 h prior to study visits 11. Females of childbearing potential and males capable of fathering a child must meet the contraception requirements (outlined in protocol section 6.3) 12. Non-lactating females 13. Females on hormone replacement therapy (estrogen or progesterone) or contraceptive therapy must be stabilized on a product and dose for at least 30 days prior to Screening 14. Have not received systemic medications with the potential to impair renal function on a frequent basis (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs]) or with ototoxic potential (e.g., quinine or salicylates), or any injectable aminoglycosides for a period of at least 14 days prior to dosing 15. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus antigen (HCV Ag) serology tests at Screening 16. No history of alcohol or drug abuse within the 6 months prior to Screening 17. Body Mass Index (BMI) of 19.0 to 30.0 kg/m² (inclusive). Participants with a lower BMI may be entered into the study at the discretion of the investigator following consultation with the Sponsor
Exclusion criteria
Exclusion criteria: 1. Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or participants who are Eloxx Pharmaceuticals employees directly involved in the conduct of the study 2. Participation in clinical study including administration of any investigational drug or device in the last 30 days or 5 half-lives (whichever is longer) prior to investigational product dosing in the current study 3. Use of prohibited medications as defined in (protocol) section 6.1 within the specified windows 4. History of any comorbidity which in the opinion of the investigator might confound the study or pose an additional risk in administering the study drug to the participant 5. History of any organ transplantation 6. Mutation consistent with autosomal dominant Alport syndrome 7. 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 8. History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) =40% 9. Evidence or history of clinically relevant psychiatric condition 10. A positive urine drug screen (amphetamines, benzodiazepines, cocaine and opiates) at Screening 11. Screening supine 12-lead electrocardiogram (ECG) demonstrating any clinically significant findings as judged by the Investigator 12. Participants with any abnormalities in clinical laboratory tests at Screening, considered by the study Investigator as clinically relevant 13. Major surgery within 180 days (6 months) of Screening 14. History of dialysis 15. Known allergy to any aminoglycoside 16. Participants with any acute medical situation unresolved within 14 days of first dose that is considered of significance by the Investigator 17. Participants with >10 dB change in threshold between audiometric Initial test to baseline test for the frequencies from 0.5 -12.5 kHz 18. Dizziness Handicap Inventory (DHI) score at screening =16 for adults, and active dizziness reported for pediatric participants.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Incidence and characteristics of adverse events (AEs) collected using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 from signing the informed consent form until the day 150/End of Study (EOS) visit 2. Injection site reactions classified and graded as per Division of AIDS (DAIDS) guidelines at the days 1, 15, 30, 45 and 60/End of Treatment (EOT) visits 3. Vital signs and physical examination performed at the initial, baseline, days 1, 15, 30, 45 and 60/EOT visits 4. Audiometric testing (including high-frequency audiometry) and tinnitus and dizziness status assessed at the initial, baseline, days 30, 60/EOT, 90, 120 and 150/EOS visits 5. 12-lead ECG performed at the initial and day 60/EOT visits 6. Clinical laboratory evaluations (haematology, chemistry, urinalysis) performed at the initial, days 1, 15, 30, 45, 60/EOT, 90, 120 and 150/EOS visits | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proteinuria measured via the urine protein/creatinine ratio (UPCR) procedure at the initial, baseline, days 1, 15, 30, 60/EOT, 90, 120 and 150/EOS visits 2. Col IV protein expression measured using a renal biopsy collected at the initial and day 60/EOT visits 3. Hematuria measured microscopically at the initial, baseline, days 1, 15, 30, 60/EOT, 90, 120 and 150/EOS visits | — |
Countries
Australia, England, United Kingdom
Outcome results
None listed