Clinical trial NCT04135495: A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With 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: cystic fibrosis
ELX-02
G542X allele
eukaryotic ribosomal selective glycoside
Lead sponsor: Eloxx Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-22
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: 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, 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


Eligibility criteria: 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

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 (AUC0-24h)
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 blood sampling at 30 min and 1 hour post dose
measure: Trough observed plasma concentration (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 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: Long Beach
country: United States
facility: Long Beach Memorial
state: California
city: Palo Alto
country: United States
facility: Stanford School of Medicine
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Calgary
country: Canada
facility: Foothills Hospital Calgary (University of Calgary)
state: Alberta
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: The University of Montreal Health Centre
state: Quebec
Study officials:
References: