- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04135495
A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With G542X Allele
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
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
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alberta
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Calgary, Alberta, Canada, T2N 4N1
- Foothills Hospital Calgary (University of Calgary)
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Ontario
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Toronto, Ontario, Canada, M5B-1W8
- St. Michael's Hospital
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Quebec
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Montreal, Quebec, Canada, H2X0A9
- The University of Montreal Health Centre
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California
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Long Beach, California, United States, 90806
- Long Beach Memorial
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Palo Alto, California, United States, 94305
- Stanford School of Medicine
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Colorado
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Denver, Colorado, United States, 80206
- National Jewish Health
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins
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Massachusetts
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Boston, Massachusetts, United States, 02451
- Boston Children's Hospital
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Ohio
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Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Males and females age 18 years and above
- 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.
- Documented SCC ≥60 mEq
- FEV1 ≥40% predicted normal for age, gender and height at Screening (Knudson Equation)
- 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:
- 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
- History of any organ transplantation
- Major surgery within 180 days (6 months) of Screening
- Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides
- Known allergy to any aminoglycoside
- Patients with any abnormality at ENT screening, that indicates the presence of a vestibular toxicity associated with prior exposure to aminoglycosides.
- Dizziness Handicap Inventory (DHI)-H score at screening must be >16.
- Patients receiving CFTR modulators within 2 months of study treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: ELX-02
Eukaryotic ribosomal selective glycoside (ERSG)
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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)
CFTR potentiator
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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From the time of first dosing through the follow-up visit, an average of approximately 9 weeks
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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
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Full PK profile 8 blood samples over 24 hours
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Day 1 of treatment periods 1, 2, 3, and 4
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Maximum observed plasma concentration (Cmax) on Day 1
Time Frame: Day 1 of treatment periods 1, 2, 3, and 4
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Full PK profile 8 blood samples over 24 hours
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Day 1 of treatment periods 1, 2, 3, and 4
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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
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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
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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
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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
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
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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
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From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
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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
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From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
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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
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From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EL-012
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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