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

NCT04135495 | Completed Phase 2 FDA Drug

• 1 other identifier: EL-012
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 10

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

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; ELX-02; G542X allele; eukaryotic ribosomal selective glycoside

Outcome Measures

Primary Outcomes (5)

• 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

• Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h)

  Full PK profile 8 blood samples over 24 hours

  Day 1 of treatment periods 1, 2, 3, and 4

• Maximum observed plasma concentration (Cmax) on Day 1

  Full PK profile 8 blood samples over 24 hours

  Day 1 of treatment periods 1, 2, 3, and 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

• 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 Outcomes (4)

• 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 expiratory volume (ppFEV1)

  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

Study Arms (1)

ELX-02

EXPERIMENTAL

Eukaryotic ribosomal selective glycoside (ERSG)

Drug: ELX-02; Drug: Ivacaftor

Interventions

ELX-02 DRUG

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)

ELX-02

Ivacaftor DRUG

CFTR potentiator

ELX-02

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eloxx Pharmaceuticals, Inc.: lead

Study Sites (10)

Long Beach Memorial

Long Beach, California, 90806, United States

Location

Stanford School of Medicine

Palo Alto, California, 94305, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02451, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Foothills Hospital Calgary (University of Calgary)

Calgary, Alberta, T2N 4N1, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B-1W8, Canada

Location

The University of Montreal Health Centre

Montreal, Quebec, H2X0A9, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ELX-02; ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2019
• First Posted: October 22, 2019
• Study Start: November 25, 2019
• Primary Completion: October 3, 2022
• Study Completion: October 3, 2022
• Last Updated: November 22, 2022

Record last verified: 2022-02

Locations

US (7); CA (3)