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A Phase 2 Study to Evaluate the Safety, Tolerability, PK and PD of ELX-02 in Cystic Fibrosis Patients With 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 cystic fibrosis, ELX-02, G542X allele, eukaryotic ribosomal selective glycoside

Eligibility Criteria

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

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

Sites / Locations

  • Long Beach Memorial
  • Stanford School of Medicine
  • National Jewish Health
  • Johns Hopkins
  • Boston Children's Hospital
  • Nationwide Children's Hospital
  • Baylor College of Medicine
  • Foothills Hospital Calgary (University of Calgary)
  • St. Michael's Hospital
  • The University of Montreal Health Centre

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 (AUC0-24h)
Full PK profile 8 blood samples over 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 concentration (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
November 21, 2022
Sponsor
Eloxx Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04135495
Brief Title
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

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
November 25, 2019 (Actual)
Primary Completion Date
October 3, 2022 (Actual)
Study Completion Date
October 3, 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
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
cystic fibrosis, ELX-02, G542X allele, eukaryotic ribosomal selective glycoside

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 eukaroyotic 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 (AUC0-24h)
Description
Full PK profile 8 blood samples over 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 blood sampling at 30 min and 1 hour post dose
Title
Trough observed plasma concentration (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 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
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and females age 18 years and above 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. Documented SCC ≥60 mEq 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 a lower BMI may be entered into the study at the discretion of the investigator following consultation with the Sponsor. Exclusion Criteria: 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 must be >16. Patients receiving CFTR modulators within 2 months of study treatment
Facility Information:
Facility Name
Long Beach Memorial
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Stanford School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02451
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Foothills Hospital Calgary (University of Calgary)
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B-1W8
Country
Canada
Facility Name
The University of Montreal Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X0A9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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