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A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD in Cystic Fibrosis Patients With at Least 1 G542X Allele

Phase 2
Completed
Conditions
Cystic Fibrosis
Interventions
Registration Number
NCT04126473
Lead Sponsor
Eloxx Pharmaceuticals, Inc.
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
17
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ELX-02ELX-02Eukaryotic ribosomal selective glycoside (ERSG)
ELX-02IvacaftorEukaryotic ribosomal selective glycoside (ERSG)
Primary Outcome Measures
NameTimeMethod
Peak observed plasma concentration (Cpeak) over timeDays 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
AEs associated with different dose levels of ELX-02From the time of first dosing through the follow-up visit, an average of approximately 9 weeks
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24)Day 1 of treatment periods 1, 2, 3, and 4

Full PK profile 8 blood samples up to 24 hours

Maximum observed plasma concentration (Cmax) on Day 1Day 1 of treatment periods 1, 2, 3, and 4

Full PK profile 8 blood samples over 24 hours

Trough observed plasma concentrations (Cpredose) over timeDays 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 Measures
NameTimeMethod
Changes from baseline in sweat chloride concentrationFrom baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Changes from baseline in percent predicted forced vital capacity (ppFVC)From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75)From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Changes from baseline in percent predicted forced expiratory volume (ppFEV1)From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4

Trial Locations

Locations (9)

Hadassah Medical Center

🇮🇱

Jerusalem, Israel

Universitätsklinikum Frankfurt

🇩🇪

Frankfurt, Germany

The Royal Prince Alfred Hospital

🇦🇺

Camperdown, New South Whales, Australia

Schneider Children's Medical Center

🇮🇱

Petach Tikvah, Israel

Carmel Medical Center

🇮🇱

Haifa, Israel

The Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

Safra Children's Hospital - Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Universitätsmedizin Essen Ruhrlandklinik

🇩🇪

Essen, North Rhine-Westphalia, Germany

The Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

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