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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04126473
• Other study ID #: EL-004
• Status: Completed
• Phase: Phase 2
• Start date: November 5, 2019
• Est. completion date: April 6, 2022

Study information

• Verified date: July 2021
• Source: Eloxx Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: April 6, 2022
• Est. primary completion date: April 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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).
• Ivacaftor
CFTR potentiator

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eloxx Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Australia,  Germany,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Eloxx Pharmaceuticals Website