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A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD in Cystic Fibrosis Patients With at Least 1 G542X Allele

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04126473
Recruitment Status : Recruiting
First Posted : October 15, 2019
Last Update Posted : March 3, 2022
Sponsor:
Information provided by (Responsible Party):
Eloxx Pharmaceuticals, Inc.

Study Description
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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 with and without ivacaftor in patients with CF with at least one G542X allele or phenotypically similar nonsense allele.

Up to 16 patients will be enrolled in the trial; up 4 patients will be homozygotes to G542X, and the remaining patients will be compound heterozygotes with G542X or phenotypically similar nonsense mutation and any Class 1 or Class 2 mutation.

Each patient will receive 5 escalating doses as follows:

  • 0.3 mg/kg per day SC
  • 0.75 mg/kg per day SC
  • 1.5 mg/kg per day SC
  • An individualized dose, as high as 3.0 mg/kg per day SC, based upon the patients observed safety and tolerability, PK at previous doses and the results of laboratory tests
  • ELX-02 1.5 mg/kg per day SC plus 150 mg ivacaftor every 12 bid

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: ELX-02 Drug: Ivacaftor Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Dose Levels of Subcutaneously Administered ELX-02 in Patients With Cystic Fibrosis With at Least One G542X Allele
Actual Study Start Date : November 5, 2019
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arms and Interventions
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Arm Intervention/treatment
Experimental: ELX-02
Eukaryotic ribosomal selective glycoside (ERSG)
 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).

Drug: Ivacaftor
CFTR potentiator


Outcome Measures
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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 9 weeks ]
  2. Area under the plasma concentration curve from time zero to 24 hours (AUC0-24) [ Time Frame: Day 1 of treatment periods 1, 2, 3, and 4 ]
    Full PK profile 8 blood samples up to 24 hours

  3. Maximum observed plasma concentration (Cmax) on Day 1 [ Time Frame: Day 1 of treatment periods 1, 2, 3, and 4 ]
    Full PK profile 8 blood samples over 24 hours

  4. Peak observed plasma concentration (Cpeak) over time [ Time Frame: Days 1, 2 and 7 of treatment periods 1-3, Days 1, 2, 7, and 14 of treatment period 4, sparse sampling, blood sampling at 30 min and 1 hour post-dose ]
  5. Trough observed plasma concentrations (Cpredose) over time [ Time Frame: Days 1, 2 and 7 of treatment periods 1-3, Days 1, 2, 7 and 14 of treatment period 4, sparse blood sampling at pre-dose ]

Secondary Outcome Measures :
  1. Changes from baseline in sweat chloride concentration [ Time Frame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4 ]
  2. Changes from baseline in percent predicted forced expiratory volume (ppFEV1) [ Time Frame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4 ]
  3. Changes from baseline in percent predicted forced vital capacity (ppFVC) [ Time Frame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4 ]
  4. Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75) [ Time Frame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  1. Males and females age 18 years and above in Germany and Israel; in countries where permitted, males and females age 16 years and above
  2. A confirmed diagnosis of nmCF with a documented G542X or phenotypically similar nonsense mutation, homozygote, or compound heterozygote with one of the specified mutations. For heterozygotes, one mutation has to be G542X or phenotypically similar nonsense mutation, and the second mutation could be and Class 1 or Class 2 mutation. Patients with one G542X or phenotypically similar nonsense allele and a second allele that is not in the above list may be potentially allowed but only after discussion on a case by case basis with and written approval from the Sponsor.
  3. Documented SCC ≥ 60 mEq/L
  4. FEV1 ≥ 40% predicted normal for age, gender and height at Screening (Knudson Equation)
  5. Body Mass Index (BMI) of 19.0 to 30.0 kg/m2 (inclusive).

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. History of any organ transplantation
  3. Major surgery within 180 days (6 months) of Screening
  4. Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides
  5. Known allergy to any aminoglycoside
  6. Patients with any abnormality at ENT screening, that indicates the presence of a vestibular toxicity associated with prior exposure to aminoglycosides.
  7. Dizziness Handicap Inventory (DHI)-H score at screening >16
  8. Patients receiving CFTR modulators within 2 months of study treatment
Contacts and Locations
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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): NCT04126473


Contacts
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Contact: Eloxx Pharmaceuticals 1-781-577-5300 CTI@eloxxpharma.com

Locations
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Australia, New South Whales
The Royal Prince Alfred Hospital Completed
Camperdown, New South Whales, Australia, 2050
Australia, South Australia
The Royal Adelaide Hospital Completed
Adelaide, South Australia, Australia
Australia, Victoria
The Alfred Hospital Completed
Melbourne, Victoria, Australia
Germany
Universitätsmedizin Essen Ruhrlandklinik Recruiting
Essen, North Rhine-Westphalia, Germany, 45239
Contact: Matthias Welsner, MD    0049 201 433 4501    Matthias.Welsner@rlk.uk-essen.de   
Contact: Gina Spangel    0049 201 433 4893    Gina.spangel@uk-essen.de   
Principal Investigator: Matthias Welsner, MD         
Universitätsklinikum Frankfurt Recruiting
Frankfurt, Germany
Contact: Wolfgang Gleiber, MD    0049 69 6301 6336    wolfgang.gleiber@kgu.de   
Contact: Tamara Metskhovrishvili    0049 69 6301 84301    tamara.metskhovrishvili@kgu.de   
Principal Investigator: Wolfgang Gleiber, MD         
Israel
Carmel Medical Center Recruiting
Haifa, Israel
Contact: Michal Shteinberg, MD    +972-4-8250419    MichalSh4@clalit.org.il   
Contact: Einat Ben Shoshan    +972-4-8250419    EinatBe2@clalit.org.il   
Principal Investigator: Michal Shteinberg, MD         
Hadassah Medical Center Recruiting
Jerusalem, Israel
Contact: Malena Cohen-Cymberknoh, MD    +972-508-573447    malena@hadassah.org.il   
Contact: Thea Pugatsch, MD    +972-2-5844702    Pthea@hadassah.org.il   
Principal Investigator: Malena Cohen-Cymberknoh, MD         
Schneider Children's Medical Center Recruiting
Petach Tikvah, Israel
Contact: Meir Mei-Zahav       meir_zahav@clalit.org.il   
Contact: Zvia Dekel    +972-03-925-3934    Zviade@clalit.org.il   
Safra Children's Hospital - Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel
Contact: Reut Ramon    972-54-5200846    Reut.Ramon@sheba.health.gov.il   
Principal Investigator: Ori Efrati, MD         
Sponsors and Collaborators
Eloxx Pharmaceuticals, Inc.
More Information
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Additional Information:

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Responsible Party: Eloxx Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04126473    
Other Study ID Numbers: EL-004
First Posted: October 15, 2019    Key Record Dates
Last Update Posted: March 3, 2022
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eloxx Pharmaceuticals, Inc.:
aminoglycoside
Nonsense Mutation
Translational read through
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
 Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action