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 Study to Evaluate the Safety, Tolerability, PK and PD in Cystic Fibrosis Patients With at Least 1 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 in patients with CF with at least one G542X
 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 and any Class 1 or Class
 2 mutation excluding F508del.

 Each patient will receive 4 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
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 mutation, homozygote, or
 compound heterozygote with one of the specified mutations. For heterozygotes, one
 mutation has to be G542X, and the second mutation could be and Class 1 or Class 2
 mutation, excluding F508del. Patients with one G542X 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