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

Genetic Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04069260
• Other study ID #: EL-003
• Status: Terminated
• Phase: Phase 2
• Start date: August 2, 2019
• Est. completion date: December 17, 2019

Study information

• Verified date: December 2019
• Source: Eloxx Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 17, 2019
• Est. primary completion date: December 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystinosis
• Fanconi Syndrome
• Genetic Disease
• Genetic Diseases, Inborn
• Nonsense Mutation

Intervention

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).

Locations

Country	Name	City	State
Canada	McGill University Health Center	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Eloxx Pharmaceuticals, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Maximum observed plasma concentration (Cmax)	Full PK profile 12 blood samples over 24 hours	Day 1 of treatment periods 1, 2, and 3
Primary	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
Primary	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
Primary	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	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

External Links

•   Eloxx Pharmaceuticals Website