A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With 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, dose-escalation 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.

In total, up to 16 patients will be enrolled in the trial; up to 4 patients will be homozygotes for G542X, and the remaining patients will be compound heterozygotes with one G542X or phenotypically similar nonsense allele and any Class 1 or Class 2 mutation.

Each patient will receive up to 5 escalating doses as follows:

• ELX-02 0.3 mg/kg per day SC
• ELX-02 0.75 mg/kg per day SC
• ELX-02 1.5 mg/kg per day SC
• An individualized dose of ELX-02, as high as 3.0 mg/kg per day SC, based on 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

Inclusion Criteria:

1. Males and females age 18 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 or phenotypically similar nonsense allele, and the second mutation has to be any Class 1 or Class 2 mutation. Patients with one G542X allele or phenotypically similar nonsense allele and a second allele that is not a Class 1 or Class 2 mutation 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
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 a lower BMI may be entered into the study at the discretion of the investigator following consultation with the Sponsor.

Exclusion Criteria:

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 must be >16.
8. Patients receiving CFTR modulators within 2 months of study treatment