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

NCT04069260 | Terminated Phase 2 FDA Drug

• 1 other identifier: EL-003
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Genetic Disease; Nonsense Mutation; Cystinosis

Keywords

aminoglycoside; translational read-through; cystinosis; nonsense mutation

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• 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

Study Arms (1)

ELX-02

EXPERIMENTAL

Eukaryotic ribosomal selective glycoside (ERSG)

Drug: ELX-02

Interventions

ELX-02 DRUG

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).

ELX-02

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eloxx Pharmaceuticals, Inc.: lead

Study Sites (1)

McGill University Health Center

Montreal, Quebec, H3H 2R9, Canada

Location

Related Links

• Eloxx Pharmaceuticals Website

MeSH Terms

Conditions

Genetic Diseases, Inborn; Cystinosis

Interventions

ELX-02

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Paul Goodyer, MD

  McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2019
• First Posted: August 28, 2019
• Study Start: August 2, 2019
• Primary Completion: December 17, 2019
• Study Completion: December 17, 2019
• Last Updated: May 27, 2020

Record last verified: 2019-12

Locations

CA (1)