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A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04135495
Recruitment Status : Completed
First Posted : October 22, 2019
Last Update Posted : November 22, 2022
Sponsor:
Information provided by (Responsible Party):
Eloxx Pharmaceuticals, Inc.

Brief Summary:

This is a Phase 2 open-label, dose-escalation 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.

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

Each patient will receive up to 5 escalating doses as follows:

  • ELX-02 0.3 mg/kg per day SC
  • ELX-02 0.75 mg/kg per day SC
  • ELX-02 1.5 mg/kg per day SC
  • An individualized dose of ELX-02, as high as 3.0 mg/kg per day SC, based on 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 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 25, 2019
Actual Primary Completion Date : October 3, 2022
Actual Study Completion Date : October 3, 2022

Resource links provided by the National Library of Medicine

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

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 eukaroyotic ribosomal selective glycoside (ERSG)

Drug: Ivacaftor
CFTR potentiator




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 (AUC0-24h) [ Time Frame: Day 1 of treatment periods 1, 2, 3, and 4 ]
    Full PK profile 8 blood samples over 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 blood sampling at 30 min and 1 hour post dose ]
  5. Trough observed plasma concentration (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 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females age 18 years and above
  2. A confirmed diagnosis of nmCF with a documented G542X mutation, homozygote, or compound heterozygote with one of the specified mutations. For heterozygotes, one mutation has to be G542X or phenotypically similar nonsense allele, and the second mutation has to be any Class 1 or Class 2 mutation. Patients with one G542X allele or phenotypically similar nonsense allele and a second allele that is not a Class 1 or Class 2 mutation 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
  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 a lower BMI may be entered into the study at the discretion of the investigator following consultation with the Sponsor.

Exclusion Criteria:

  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 must be >16.
  8. Patients receiving CFTR modulators within 2 months of study treatment

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): NCT04135495


Locations
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United States, California
Long Beach Memorial
Long Beach, California, United States, 90806
Stanford School of Medicine
Palo Alto, California, United States, 94305
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02451
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Canada, Alberta
Foothills Hospital Calgary (University of Calgary)
Calgary, Alberta, Canada, T2N 4N1
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada, M5B-1W8
Canada, Quebec
The University of Montreal Health Centre
Montreal, Quebec, Canada, H2X0A9
Sponsors and Collaborators
Eloxx Pharmaceuticals, Inc.
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Responsible Party: Eloxx Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04135495    
Other Study ID Numbers: EL-012
First Posted: October 22, 2019    Key Record Dates
Last Update Posted: November 22, 2022
Last Verified: February 2022

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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.:
cystic fibrosis
ELX-02
G542X allele
eukaryotic ribosomal selective glycoside
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