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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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ELX-02
Ivacaftor
Sponsored by
Eloxx Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring aminoglycoside, Nonsense Mutation, Translational read through

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Royal Prince Alfred Hospital
  • The Royal Adelaide Hospital
  • The Alfred Hospital
  • Universitätsmedizin Essen Ruhrlandklinik
  • Universitätsklinikum Frankfurt
  • Carmel Medical Center
  • Hadassah Medical Center
  • Schneider Children's Medical Center
  • Safra Children's Hospital - Chaim Sheba Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ELX-02

Arm Description

Eukaryotic ribosomal selective glycoside (ERSG)

Outcomes

Primary Outcome Measures

AEs associated with different dose levels of ELX-02
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24)
Full PK profile 8 blood samples up to 24 hours
Maximum observed plasma concentration (Cmax) on Day 1
Full PK profile 8 blood samples over 24 hours
Peak observed plasma concentration (Cpeak) over time
Trough observed plasma concentrations (Cpredose) over time

Secondary Outcome Measures

Changes from baseline in sweat chloride concentration
Changes from baseline in percent predicted forced expiratory volume (ppFEV1)
Changes from baseline in percent predicted forced vital capacity (ppFVC)
Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75)

Full Information

First Posted
August 16, 2019
Last Updated
August 17, 2023
Sponsor
Eloxx Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04126473
Brief Title
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

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
November 5, 2019 (Actual)
Primary Completion Date
April 6, 2022 (Actual)
Study Completion Date
April 6, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eloxx Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
aminoglycoside, Nonsense Mutation, Translational read through

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ELX-02
Arm Type
Experimental
Arm Description
Eukaryotic ribosomal selective glycoside (ERSG)
Intervention Type
Drug
Intervention Name(s)
ELX-02
Intervention Description
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 eukaryotic ribosomal selective glycoside (ERSG).
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Intervention Description
CFTR potentiator
Primary Outcome Measure Information:
Title
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
Title
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24)
Description
Full PK profile 8 blood samples up to 24 hours
Time Frame
Day 1 of treatment periods 1, 2, 3, and 4
Title
Maximum observed plasma concentration (Cmax) on Day 1
Description
Full PK profile 8 blood samples over 24 hours
Time Frame
Day 1 of treatment periods 1, 2, 3, and 4
Title
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
Title
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 Outcome Measure Information:
Title
Changes from baseline in sweat chloride concentration
Time Frame
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Title
Changes from baseline in percent predicted forced expiratory volume (ppFEV1)
Time Frame
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Title
Changes from baseline in percent predicted forced vital capacity (ppFVC)
Time Frame
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4
Title
Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75)
Time Frame
From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Patients must meet the following criteria to participate in this study: Males and females age 18 years and above in Germany and Israel; in countries where permitted, males and females age 16 years and above 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. Documented SCC ≥ 60 mEq/L FEV1 ≥ 40% predicted normal for age, gender and height at Screening (Knudson Equation) 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: 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 History of any organ transplantation Major surgery within 180 days (6 months) of Screening Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides Known allergy to any aminoglycoside Patients with any abnormality at ENT screening, that indicates the presence of a vestibular toxicity associated with prior exposure to aminoglycosides. Dizziness Handicap Inventory (DHI)-H score at screening >16 Patients receiving CFTR modulators within 2 months of study treatment
Facility Information:
Facility Name
The Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Whales
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Universitätsmedizin Essen Ruhrlandklinik
City
Essen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
45239
Country
Germany
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt
Country
Germany
Facility Name
Carmel Medical Center
City
Haifa
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
Country
Israel
Facility Name
Schneider Children's Medical Center
City
Petach Tikvah
Country
Israel
Facility Name
Safra Children's Hospital - Chaim Sheba Medical Center
City
Ramat Gan
Country
Israel

12. IPD Sharing Statement

Links:
URL
http://www.eloxxpharma.com
Description
Eloxx Pharmaceuticals Website

Learn more about this trial

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

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