Clinical trial NCT05448755: A Study of ELX-02 in Patients With Alport Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alport Syndrome
Keywords: Aminoglycoside
Nonsense Mutation
Translational read through
Lead sponsor: Eloxx Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-07
Enrollment: 8
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: The incidence and characteristics of adverse events
timeFrame: From the time of first dosing through the end of the follow-up period, a total of 5 months
Secondary outcomes:
measure: Change in proteinuria
timeFrame: From screening assessment to end of study treatment and end of follow up period, two and five months respectively
measure: Change in Col IV expression in renal biopsy
timeFrame: From biopsy collected at screening to the biopsy collected at the end of study treatment, a two months interval
measure: Change in hematuria
timeFrame: From screening assessment to end of study treatment and end of follow up period, two and five months respectively
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Monash Medical Center
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
References: