Cystic fibrosis (CF) MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: ELX-02
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Not Assigned
CAS Number: 1375073-94-1
Current Sponsor code: ELX-02
Concentration unit: mg milligr
Sponsors
Eloxx Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial 2. Understands, and is willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures 3. Males and females age 18 years and above; in countries where permitted, males and females age 16 and above 4. 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 a G542X or phenotypically similar nonsense mutation, and the second mutation should be any 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. 5. Documented SCC = 60 mEq 6. FEV1 = 40% predicted normal for age, gender and height at Screening (Knudson Equation) 7. Stable regimen of oral CF medications, inhaled antibiotics, dornase alfa, and hypertonic saline, and physiotherapy for the period 28 days prior to Screening 8. Non-smokers for at least 180 days (6 months) prior to Screening 9. Must be willing to abstain from strenuous exercise during the 24 hours prior study visits 10. Females of childbearing potential and males capable of fathering a child must meet the contraception requirements outlined in Section ?6.4 11. Non-lactating females 12. Females on hormone replacement therapy (estrogen or progesterone) or contraceptive therapy must be stabilized on a product and dose for at least 30 days prior to Screening 13. Glomerular filtration rate (GFR) of > 60 mL/min/1.73m2 at Screening (GFR to be calculated using the Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula 14. Have not received systemic medications with potential to impair renal function on a frequent basis (e.g., non steroidal anti inflammatory drugs [NSAIDs]) or with ototoxic potential (e.g., quinine or salicylates), or any injectable aminoglycosides for a period of at least 14 days prior to dosing 15. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus antigen (HCV Ag) serology tests at Screening 16. No history of alcohol or drug abuse within the 6 months prior to Screening 17. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or patients who are Eloxx Pharmaceuticals employees directly involved in the conduct of the study 2. 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 3. Use of prohibited medications as defined in Section ?6.1 within the specified windows 4. History of any comorbidity which in the opinion of the investigator might confound the study or pose an additional risk in administering the study drug to the patient 5. History of any organ transplantation 6. Liver disease characterized by cirrhosis or portal hypertension. Patients with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or a total bilirubin 3.0 times the upper limit of normal (ULN) will be excluded 7. History of clinically significant adrenal disease needing hormone replacement therapy 8. History of congestive heart failure diagnosed clinically or with documented left ventricular ejection fraction (LVEF) = 40% 9. Evidence or history of clinically relevant psychiatric condition 10. A positive urine drug screen (amphetamines, benzodiazepines, cocaine and opiates) at Screening 11. Screening supine 12-lead electrocardiogram (ECG) demonstrating any clinically significant findings as judged by the Investigator 12. Patients with any abnormalities in clinical laboratory tests at Screening, considered by the study physician as clinically relevant 13. Major surgery within 180 days (6 months) of Screening 14. Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides 15. Known allergy to any aminoglycoside 16. Patients with any acute medical situation not related to CF (e.g., gastroenteritis) unresolved within 14 days of first dose that is considered of significance by the Investigator 17. Patients with any abnormality at ENT screening, that indicates the presence of a vestibular toxicity associated with prior exposure to aminoglycosides. 18. Dizziness Handicap Inventory (DHI)-H score at screening >16. 19. Patients receiving CFTR modulators or potentiators as defined in Section ?6.1 within 2 months of study enrollment 20. Patients unable to avoid foods or drinks that contain grapefruit or Seville oranges, as these may affect the amount of ivacaftor in the body. Patients who meet this exclusion criterion and have already started the study prior to Protocol Amendment 5.0 will not be allowed to proceed to Treatment Period 5 21. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. Patients who meet this exclusion criterion and have already started the study prior to Protocol Amendment 5.0 will not be allowed to proceed to Treatment Period 5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the safety and tolerability of different dose levels and exposures of ELX-02 administered subcutaneously (SC), as monotherapy and in combination with ivacaftor in patients with CF carrying at least one G542X CFTR or phenotypically similar nonsense allele. 2. To study the PK of multiple SC doses of ELX-02 as monotherapy and in combination with ivacaftor, in patients with CF. ;Secondary Objective: 1. To study the PD of multiple doses of ELX-02 as monotherapy and in combination with ivacaftor on sweat chloride concentration (SCC). 2. To study the PD of multiple doses of ELX-02 as monotherapy and in combination with ivacaftor on pulmonary function (forced expiratory volume [FEV], forced vital capacity [FVC], and forced expiratory flow at 25-75%] FEF). ;Primary end point(s): Primary Endpoints: 1. The incidence and characteristics of adverse events (AEs). Other safety assessments will include injection site reactions (DAIDS Grading Scale) and changes from baseline in vital signs, physical examination, electrocardiograms, blood and urine safety laboratory tests, audiometric testing (including high frequency audiometry) and Tinnitus Handicap Inventory (THI) and Dizziness Handicap Inventory (DHI) questionnaires. 2. Plasma and urine PK parameters of ELX-02 following the first dose and at steady state, at each dose level (Treatment Periods 1-5). 3. Plasma PK parameters of ivacaftor following the first dose and at steady state (Treatment Period 5);Timepoint(s) of evaluation of this end point: 1. From screening until End-of-Study (EOS) visit; 2. Blood PK parameters: D1, D2, D7 of treatment periods 1-3, Day 14 of treatment period 4, End-of-Study (EOS) visit. Urine PK parameters: D1, D2 of all treatment periods | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: 1. PD as assessed by changes from baseline in SCC following ELX-02 treatment 2. PD as assessed by changes from baseline in pulmonary function including FEV1, FVC, and FEF25-75, absolute values and percent predicted. 3. Dose and PK relationship. ;Timepoint(s) of evaluation of this end point: During treatment | — |
Countries
Australia, Germany, Israel
Contacts
Public ContactTim Kachmar
Eloxx Pharmaceuticals, Inc.
Outcome results
None listed