Clinical trial NCT04126473: A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD in Cystic Fibrosis Patients With at Least 1 G542X Allele
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: aminoglycoside
Nonsense Mutation
Translational read through
Lead sponsor: Eloxx Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-15
Enrollment: 17
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: AEs associated with different dose levels of ELX-02
timeFrame: From the time of first dosing through the follow-up visit, an average of approximately 9 weeks
measure: Area under the plasma concentration curve from time zero to 24 hours (AUC0-24)
timeFrame: Day 1 of treatment periods 1, 2, 3, and 4
measure: Maximum observed plasma concentration (Cmax) on Day 1
timeFrame: Day 1 of treatment periods 1, 2, 3, and 4
measure: Peak observed plasma concentration (Cpeak) over time
timeFrame: 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
measure: Trough observed plasma concentrations (Cpredose) over time
timeFrame: 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:
measure: Changes from baseline in sweat chloride concentration
timeFrame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
measure: Changes from baseline in percent predicted forced expiratory volume (ppFEV1)
timeFrame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
measure: Changes from baseline in percent predicted forced vital capacity (ppFVC)
timeFrame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
measure: Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75)
timeFrame: From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: The Royal Prince Alfred Hospital
state: New South Whales
city: Adelaide
country: Australia
facility: The Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Essen
country: Germany
facility: Universitätsmedizin Essen Ruhrlandklinik
state: North Rhine-Westphalia
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikvah
country: Israel
facility: Schneider Children's Medical Center
city: Ramat Gan
country: Israel
facility: Safra Children's Hospital - Chaim Sheba Medical Center
Study officials:
References: