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
Overview
- Phase
- Phase 2
- Intervention
- ELX-02
- Conditions
- Cystic Fibrosis
- Sponsor
- Eloxx Pharmaceuticals, Inc.
- Enrollment
- 17
- Locations
- 9
- Primary Endpoint
- Peak observed plasma concentration (Cpeak) over time
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
ELX-02
Eukaryotic ribosomal selective glycoside (ERSG)
Intervention: ELX-02
ELX-02
Eukaryotic ribosomal selective glycoside (ERSG)
Intervention: Ivacaftor
Outcomes
Primary Outcomes
Peak observed plasma concentration (Cpeak) over time
Time Frame: 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
AEs associated with different dose levels of ELX-02
Time Frame: From 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)
Time Frame: 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 1
Time Frame: Day 1 of treatment periods 1, 2, 3, and 4
Full PK profile 8 blood samples over 24 hours
Trough observed plasma concentrations (Cpredose) over time
Time Frame: 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
- Changes from baseline in sweat chloride concentration(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 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)