A Phase 2 Study of ELX-02 in Patients With Nephropathic Cystinosis

A Phase 2, Single Center, Open-Label, Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Daily Subcutaneously Administered ELX-02 in Patients With Nephropathic Cystinosis Bearing One or More CTNS Gene (Cystinosin) Nonsense Mutations

This is a Phase 2 open label study to evaluate the safety, tolerability, PK, and PD of multiple dose levels of SC administered ELX-02 in patients with cystinosis with nonsense mutation in at least one allele.

Six patients will be enrolled in the trial.

The study will comprise of the following periods for each patient:

• A screening period of up to 6 weeks
• A total treatment period of 4 weeks
• A safety follow-up period of 4 weeks after the last treatment

Each patient will receive three escalating doses as follows:

• Treatment period 1: ELX-02 0.5 mg/kg SC daily for 7 days (total dose not to exceed 3.5 mg/kg for this week; the daily dose will be individualized to achieve the target weekly exposure of about 47.5 µg*h/mL)
• Treatment period 2: ELX-02 1.0 mg/kg SC daily for 7 days (total dose not to exceed 7.0 mg/kg for this week; the daily dose will be individualized to achieve the target weekly exposure of about 95 µg*h/mL)
• Treatment period 3: ELX-02 2.0 mg/kg SC daily for 14 days (total dose not to exceed 14 mg/kg for these two weeks; the daily dose will be individualized to achieve the target weekly exposure of about 190 µg*h/mL)

Study Overview

• Status: Terminated
• Conditions: Genetic Disease; Cystinosis; Nonsense Mutation
• Intervention / Treatment: Drug: ELX-02

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3H 2R9
      • McGill University Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients must meet all of the following criteria to participate in this study:

1. Male or female patients who, at the time of screening, are 18 years of age or older (Cohort 1) or ≥12 years of age (Cohort 2)
2. A diagnosis of nephropathic cystinosis and biallelic CTNS mutations, including at least one nonsense mutation
3. Patients should have a mild to moderate disease estimated glomerular filtration rate ≥40 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula
4. Body mass index of 19.0 to 30.0 kg/m2. Patients with a lower BMI may be entered into the study at the discretion of the Investigator following consultation with the Sponsor
5. Renal transplant permitted with stable graft function (serum creatinine) for 3 months prior to Screening

Patients with any of the following characteristics/conditions will not be included in the study:

1. 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
2. Concomitant use of cysteamine bitartrate from 7 days prior to baseline until 7 days following final administration ELX-02
3. An average systolic blood pressure and/or diastolic blood pressure ≥95th percentile for sex, age, and height on 3 or more occasions during the screening period
4. Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides
5. Known relevant allergy or hypersensitivity to aminoglycosides

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ELX-02; Eukaryotic ribosomal selective glycoside (ERSG)	Drug: ELX-02; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs associated with different dose levels of ELX-02		From the time of first dosing through the follow-up visit, an average of approximately 10 weeks
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h)	Full PK profile 12 blood samples over 24 hours	Day 1 of treatment periods 1, 2, and 3
Maximum observed plasma concentration (Cmax)	Full PK profile 12 blood samples over 24 hours	Day 1 of treatment periods 1, 2, and 3
Observed plasma concentration at 1 hour post dose (C1h)	Sparse sampling, blood sampling only, pre-dose and 1 hour post dose	Days 1, 2, 5, and 7 of treatment periods 1-2; Days 1, 2, 5, 7, 10, and 14 of treatment period 3
Amount of ELX-02 excreted in urine from 0 to 24 hours (Ae24h)	6 urine collections over 24 hours	Day 1 of treatment periods 1, 2, and 3
Renal clearance on Day 1 (Ae24h/plasma AUC0-24h)	6 urine collections over 24 hours	Day 1 of treatment periods 1, 2, and 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes from baseline in WBC cystine levels	Screening; Days 1, 2, 5, and 7 of treatment periods 1-2; Days 1, 2, 5, 7, 10, and 14 of treatment period 3, and 4-week safety follow-up

Collaborators and Investigators

• Sponsor: Eloxx Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Paul Goodyer, MD, McGill University

Publications and helpful links

Helpful Links

• Eloxx Pharmaceuticals Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 2, 2019
• Primary Completion (ACTUAL): December 17, 2019
• Study Completion (ACTUAL): December 17, 2019

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (ACTUAL): August 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 27, 2020
• Last Update Submitted That Met QC Criteria: May 22, 2020
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: aminoglycoside; cystinosis; translational read-through; nonsense mutation
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Renal Tubular Transport, Inborn Errors; Fanconi Syndrome; Genetic Diseases, Inborn; Cystinosis
• Other Study ID Numbers: EL-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No