A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With G542X Allele

• Sponsor: Eloxx Pharmaceuticals, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04135495
• Collaborator: (none)
• Enrollment: 16
• Locations: 10
• Arm: 1
• Anticipated Duration (Months): 32.2
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: ELX-02; Drug: Ivacaftor	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 25, 2019
• Anticipated Primary Completion Date: Jul 31, 2022
• Anticipated Study Completion Date: Jul 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ELX-02 Eukaryotic ribosomal selective glycoside (ERSG)	Drug: ELX-02; ELX-02 is a small molecule, new chemical entity being developed for the treatment of genetic diseases caused by nonsense mutations. ELX-02 is a eukaroyotic ribosomal selective glycoside (ERSG); Drug: Ivacaftor; CFTR potentiator

Outcome Measures

Primary Outcome Measures

1. AEs associated with different dose levels of ELX-02 [From the time of first dosing through the follow-up visit, an average of approximately 9 weeks]

2. Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h) [Day 1 of treatment periods 1, 2, 3, and 4]

   Full PK profile 8 blood samples over 24 hours

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

   Full PK profile 8 blood samples over 24 hours

4. Peak observed plasma concentration (Cpeak) over time [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]

5. Trough observed plasma concentration (Cpredose) over time [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 Outcome Measures

1. 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]

2. 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]

3. 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]

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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial	Long Beach	California	United States	90806
2	Stanford School of Medicine	Palo Alto	California	United States	94305
3	National Jewish Health	Denver	Colorado	United States	80206
4	Johns Hopkins	Baltimore	Maryland	United States	21287
5	Boston Children's Hospital	Boston	Massachusetts	United States	02451
6	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
7	Baylor College of Medicine	Houston	Texas	United States	77030
8	Foothills Hospital Calgary (University of Calgary)	Calgary	Alberta	Canada	T2N 4N1
9	St. Michael's Hospital	Toronto	Ontario	Canada	M5B-1W8
10	The University of Montreal Health Centre	Montreal	Quebec	Canada	H2X0A9

Sponsors and Collaborators

• Eloxx Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eloxx Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04135495
• Other Study ID Numbers: EL-012
• First Posted: Oct 22, 2019
• Last Update Posted: Feb 16, 2022
• Last Verified: Feb 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eloxx Pharmaceuticals, Inc.: cystic fibrosis; ELX-02; G542X allele; eukaryotic ribosomal selective glycoside
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor

Study Results

No Results Posted as of Feb 16, 2022