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

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ivacaftor; Drug: ELX-02

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eloxx Pharmaceuticals; Phone Number: 1-781-577-5300; Email: CTI@eloxxpharma.com

Study Locations

• Australia
  • New South Whales
    • Camperdown, New South Whales, Australia, 2050
      • The Royal Prince Alfred Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • The Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia
      • The Alfred Hospital
• Germany
  • Frankfurt, Germany
    • Universitatsklinikum Frankfurt
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45239
      • Universitätsmedizin Essen Ruhrlandklinik
• Israel
  • Haifa, Israel
    • Carmel Medical Center
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Petach Tikvah, Israel
    • Schneider Children's Medical Center
  • Ramat Gan, Israel
    • Safra Children's Hospital - Chaim Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ELX-02; Eukaryotic ribosomal selective glycoside (ERSG)	Drug: Ivacaftor; CFTR potentiator; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs associated with different dose levels of ELX-02		From the time of first dosing through the follow-up visit, an average of approximately 9 weeks
Maximum observed plasma concentration (Cmax) on Day 1	Full PK profile 8 blood samples over 24 hours	Day 1 of treatment periods 1, 2, 3, and 4
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24)	Full PK profile 8 blood samples up to 24 hours	Day 1 of treatment periods 1, 2, 3, and 4
Peak observed plasma concentration (Cpeak) over time		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
Trough observed plasma concentrations (Cpredose) over time		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

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

Collaborators and Investigators

• Sponsor: Eloxx Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Eloxx Pharmaceuticals Website

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): April 6, 2022
• Study Completion (Actual): April 6, 2022

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: aminoglycoside; Translational read through; Nonsense Mutation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: EL-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No