A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With G542X Allele

• ClinicalTrials.gov Identifier: NCT04135495
• Recruitment Status: Completed
• First Posted: October 22, 2019
• Last Update Posted: November 22, 2022
• Sponsor: Eloxx Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Eloxx Pharmaceuticals, Inc.

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

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.

More Information

• Responsible Party: Eloxx Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04135495
• Other Study ID Numbers: EL-012
• First Posted: October 22, 2019
• Last Update Posted: November 22, 2022
• Last Verified: February 2022

• 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:

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