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

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ClinicalTrials.gov Identifier: NCT04069260
Recruitment Status : Recruiting
First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Eloxx Pharmaceuticals, Inc.

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)

Condition or disease Intervention/treatment Phase
Genetic Disease Nonsense Mutation Cystinosis Drug: ELX-02 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
Experimental: ELX-02
Synthetic aminoglycoside
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).




Primary Outcome Measures :
  1. 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 ]
  2. Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h) [ Time Frame: Day 1 of treatment periods 1, 2, and 3 ]
    Full PK profile 12 blood samples over 24 hours

  3. Maximum observed plasma concentration (Cmax) [ Time Frame: Day 1 of treatment periods 1, 2, and 3 ]
    Full PK profile 12 blood samples over 24 hours

  4. Observed plasma concentration at 1 hour post dose (C1h) [ 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 ]
    Sparse sampling, blood sampling only, pre-dose and 1 hour post dose

  5. Amount of ELX-02 excreted in urine from 0 to 24 hours (Ae24h) [ Time Frame: Day 1 of treatment periods 1, 2, and 3 ]
    6 urine collections over 24 hours

  6. Renal clearance on Day 1 (Ae24h/plasma AUC0-24h) [ Time Frame: Day 1 of treatment periods 1, 2, and 3 ]
    6 urine collections over 24 hours


Secondary Outcome Measures :
  1. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04069260


Contacts
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Contact: Andi Leubitz 1-781-577-5300 andi@eloxxpharma.com

Locations
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Canada, Quebec
McGill University Health Center Recruiting
Montréal, Quebec, Canada, H3H 2R9
Contact: Paul Goodyer, MD    1-514-412-4400 ext 22584    paul.goodyer@mcgill.ca   
Contact: Murielle Akpa, PhD    1-514-412-4400 ext 22953    murielle.akpa@mcgill.ca   
Sponsors and Collaborators
Eloxx Pharmaceuticals, Inc.
Investigators
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Principal Investigator: Paul Goodyer, MD McGill University

Additional Information:
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Responsible Party: Eloxx Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04069260     History of Changes
Other Study ID Numbers: EL-003
First Posted: August 26, 2019    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eloxx Pharmaceuticals, Inc.:
aminoglycoside
translational read-through
cystinosis
nonsense mutation
Additional relevant MeSH terms:
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Fanconi Syndrome
Genetic Diseases, Inborn
Cystinosis
Lysosomal Storage Diseases
Metabolism, Inborn Errors
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases