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

NCT04126473 | Completed Phase 2

• 1 other identifier: EL-004
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 9

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

Conditions

Cystic Fibrosis

Keywords

aminoglycoside; Nonsense Mutation; Translational read through

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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 Outcomes (4)

• 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

Study Arms (1)

ELX-02

EXPERIMENTAL

Eukaryotic ribosomal selective glycoside (ERSG)

Drug: ELX-02; Drug: Ivacaftor

Interventions

ELX-02 DRUG

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).

ELX-02

Ivacaftor DRUG

CFTR potentiator

ELX-02

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eloxx Pharmaceuticals, Inc.: lead

Study Sites (9)

The Royal Prince Alfred Hospital

Camperdown, New South Whales, 2050, Australia

Location

The Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

Universitätsmedizin Essen Ruhrlandklinik

Essen, North Rhine-Westphalia, 45239, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, Germany

Location

Carmel Medical Center

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Schneider Children's Medical Center

Petach Tikvah, Israel

Location

Safra Children's Hospital - Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Related Links

• Eloxx Pharmaceuticals Website

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ELX-02; ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2019
• First Posted: October 15, 2019
• Study Start: November 5, 2019
• Primary Completion: April 6, 2022
• Study Completion: April 6, 2022
• Last Updated: August 21, 2023

Record last verified: 2021-07

Locations

IL (4); AU (3); DE (2)