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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04126473




Registration number
NCT04126473
Ethics application status
Date submitted
16/08/2019
Date registered
15/10/2019
Date last updated
21/08/2023

Titles & IDs
Public title
A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD in Cystic Fibrosis Patients With at Least 1 G542X Allele
Scientific 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
Secondary ID [1] 0 0
EL-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ELX-02
Treatment: Drugs - Ivacaftor

Experimental: ELX-02 - Eukaryotic ribosomal selective glycoside (ERSG)


Treatment: Drugs: 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).

Treatment: Drugs: Ivacaftor
CFTR potentiator
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AEs associated with different dose levels of ELX-02
Timepoint [1] 0 0
From the time of first dosing through the follow-up visit, an average of approximately 9 weeks
Primary outcome [2] 0 0
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24)
Timepoint [2] 0 0
Day 1 of treatment periods 1, 2, 3, and 4
Primary outcome [3] 0 0
Maximum observed plasma concentration (Cmax) on Day 1
Timepoint [3] 0 0
Day 1 of treatment periods 1, 2, 3, and 4
Primary outcome [4] 0 0
Peak observed plasma concentration (Cpeak) over time
Timepoint [4] 0 0
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 outcome [5] 0 0
Trough observed plasma concentrations (Cpredose) over time
Timepoint [5] 0 0
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 [1] 0 0
Changes from baseline in sweat chloride concentration
Timepoint [1] 0 0
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Secondary outcome [2] 0 0
Changes from baseline in percent predicted forced expiratory volume (ppFEV1)
Timepoint [2] 0 0
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Secondary outcome [3] 0 0
Changes from baseline in percent predicted forced vital capacity (ppFVC)
Timepoint [3] 0 0
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Secondary outcome [4] 0 0
Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75)
Timepoint [4] 0 0
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4

Eligibility
Key inclusion criteria
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
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/04/2022
Sample size
Target
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
New South WhalesSA,VIC
Recruitment hospital [1] 0 0
The Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
North Rhine-Westphalia
Country [2] 0 0
Germany
State/province [2] 0 0
Frankfurt
Country [3] 0 0
Israel
State/province [3] 0 0
Haifa
Country [4] 0 0
Israel
State/province [4] 0 0
Jerusalem
Country [5] 0 0
Israel
State/province [5] 0 0
Petach Tikvah
Country [6] 0 0
Israel
State/province [6] 0 0
Ramat Gan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eloxx Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT04126473
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04126473