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

Primary Purpose

Genetic Disease, Nonsense Mutation, Cystinosis

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

ELX-02

About this trial

This is an interventional treatment trial for Genetic Disease focused on measuring aminoglycoside, translational read-through, cystinosis, nonsense mutation

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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)
A diagnosis of nephropathic cystinosis and biallelic CTNS mutations, including at least one nonsense mutation
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
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
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:

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
Concomitant use of cysteamine bitartrate from 7 days prior to baseline until 7 days following final administration ELX-02
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
Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides
Known relevant allergy or hypersensitivity to aminoglycosides

Sites / Locations

McGill University Health Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ELX-02

Arm Description

Eukaryotic ribosomal selective glycoside (ERSG)

Outcomes

Primary Outcome Measures

AEs associated with different dose levels of ELX-02

Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h)

Full PK profile 12 blood samples over 24 hours

Maximum observed plasma concentration (Cmax)

Full PK profile 12 blood samples over 24 hours

Observed plasma concentration at 1 hour post dose (C1h)

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)

6 urine collections over 24 hours

Renal clearance on Day 1 (Ae24h/plasma AUC0-24h)

6 urine collections over 24 hours

Secondary Outcome Measures

Changes from baseline in WBC cystine levels

Full Information

NCT ID

NCT04069260

First Posted

August 16, 2019

Last Updated

May 22, 2020

Sponsor

Eloxx Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04069260

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Terminated

Why Stopped

Due to study design limitations, this study has been discontinued and will not proceed with the 2nd cohort as contemplated in the original protocol.

Study Start Date

August 2, 2019 (Actual)

Primary Completion Date

December 17, 2019 (Actual)

Study Completion Date

December 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eloxx Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Genetic Disease, Nonsense Mutation, Cystinosis

Keywords

aminoglycoside, translational read-through, cystinosis, nonsense mutation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ELX-02

Arm Type

Experimental

Arm Description

Eukaryotic ribosomal selective glycoside (ERSG)

Intervention Type

Drug

Intervention Name(s)

ELX-02

Intervention Description

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).

Primary Outcome Measure Information:

Title

AEs associated with different dose levels of ELX-02

Time Frame

From the time of first dosing through the follow-up visit, an average of approximately 10 weeks

Title

Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h)

Description

Full PK profile 12 blood samples over 24 hours

Time Frame

Day 1 of treatment periods 1, 2, and 3

Title

Maximum observed plasma concentration (Cmax)

Description

Full PK profile 12 blood samples over 24 hours

Time Frame

Day 1 of treatment periods 1, 2, and 3

Title

Observed plasma concentration at 1 hour post dose (C1h)

Description

Sparse sampling, blood sampling only, pre-dose and 1 hour post dose

Time Frame

Days 1, 2, 5, and 7 of treatment periods 1-2; Days 1, 2, 5, 7, 10, and 14 of treatment period 3

Title

Amount of ELX-02 excreted in urine from 0 to 24 hours (Ae24h)

Description

6 urine collections over 24 hours

Time Frame

Day 1 of treatment periods 1, 2, and 3

Title

Renal clearance on Day 1 (Ae24h/plasma AUC0-24h)

Description

6 urine collections over 24 hours

Time Frame

Day 1 of treatment periods 1, 2, and 3

Secondary Outcome Measure Information:

Title

Changes from baseline in WBC cystine levels

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Patients must meet all of the following criteria to participate in this study: 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) A diagnosis of nephropathic cystinosis and biallelic CTNS mutations, including at least one nonsense mutation 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 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 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: 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 Concomitant use of cysteamine bitartrate from 7 days prior to baseline until 7 days following final administration ELX-02 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 Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides Known relevant allergy or hypersensitivity to aminoglycosides

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul Goodyer, MD

Organizational Affiliation

McGill University

Official's Role

Principal Investigator

Facility Information:

Facility Name

McGill University Health Center

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H3H 2R9

Country

Canada

12. IPD Sharing Statement

Links:

URL

http://www.eloxxpharma.com

Description

Eloxx Pharmaceuticals Website

Learn more about this trial

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

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