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

NCT04069260 — Phase 2, Terminated, 3 participants, Eloxx Pharmaceuticals, Inc.

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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

Registry	NCT04069260
Status	Terminated - Due to study design limitations, this study has been discontinued and will not proceed with the 2nd cohort as contemplated in the original protocol.
Phase	Phase 2
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	3 (Actual)
Sponsor	Eloxx Pharmaceuticals, Inc. (Industry)
Conditions	Genetic Disease, Nonsense Mutation, Cystinosis
Interventions	ELX-02 (Drug)
Dates	start 2019-08-02, primary completion 2019-12-17, completion 2019-12-17, first posted 2019-08-28, last updated 2020-05-27
Locations	1 site in Canada

-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)

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+Arms and interventions

Arm	Type	Interventions	Description
ELX-02	Experimental	Drug: ELX-02	Eukaryotic ribosomal selective glycoside (ERSG)

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).

+Outcome measures

Primary outcomes

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) [Day 1 of treatment periods 1, 2, and 3]: Full PK profile 12 blood samples over 24 hours
Maximum observed plasma concentration (Cmax) [Day 1 of treatment periods 1, 2, and 3]: Full PK profile 12 blood samples over 24 hours
Observed plasma concentration at 1 hour post dose (C1h) [Days 1, 2, 5, and 7 of treatment periods 1-2; Days 1, 2, 5, 7, 10, and 14 of treatment period 3]: Sparse sampling, blood sampling only, pre-dose and 1 hour post dose
Amount of ELX-02 excreted in urine from 0 to 24 hours (Ae24h) [Day 1 of treatment periods 1, 2, and 3]: 6 urine collections over 24 hours
Renal clearance on Day 1 (Ae24h/plasma AUC0-24h) [Day 1 of treatment periods 1, 2, and 3]: 6 urine collections over 24 hours

Secondary outcomes

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]

+Eligibility

Sex: All, ages: 12 Years to any

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

+Locations (1)

Facility	City	Country	Status
McGill University Health Center	Montreal, Quebec	Canada

+Investigators

Paul Goodyer, MD, Principal investigator, McGill University