Phase 1 Study of ELX-02 in Healthy Adult Subjects

NCT03309605 | Completed Phase 1 Results DMC

• 1 other identifier: EL-002
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 Multiple Ascending Dose Study in Normal Healthy Volunteers

Conditions

Genetic Disease; Nonsense Mutation

Keywords

Translational read through

Outcome Measures

Primary Outcomes (18)

• Pharmacokinetic Parameters - Plasma AUC0-24

  Day 1 Area under the curve (AUC0-24) of ELX-02 plasma concentration following the subcutaneous (SC) dose on Day 1 to 24 hours post-ose

  Day 1: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, post-dose

• Pharmacokinetic Parameters- Plasma AUC0-24

  Day 29 Area under the curve (AUC0-24) of ELX-02 plasma concentration following the subcutaneous (SC) dose on Day 29 to 24 hours post-dose

  Day 29: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, post-dose

• Pharmacokinetic Parameters - Plasma Cmax

  Day 1 Peak Plasma Concentration (Cmax) of ELX-02 following the subcutaneous (SC) dose on Day 1 to 72 hours post-dose

  Day 1: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, 36h, 48h, 72h, post-dose

• Pharmacokinetic Parameters - Plasma Cmax

  Day 29 Peak Plasma Concentration (Cmax) of ELX-02 following the subcutaneous (SC) dose on Day 29 to 72 hours post-dose

  Day 29: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, 36h, 48h, 72h post-dose

• Pharmacokinetic Parameter - Plasma AUC0-inf

  Day 1 Area under the curve (AUC0-inf) of ELX-02 plasma concentration following the subcutaneous (SC) dose on Day 1 extrapolated to infinity

  Day 1: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, 36h, 48h, 72h post dose

• Pharmacokinetic Parameter - Plasma AUC0-inf

  Day 29 Area under the curve (AUC0-inf) of ELX-02 plasma concentration following the subcutaneous (SC) dose on Day 29 extrapolated to infinity

  Day 29: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, 36h, 48h, 72h post dose

• Pharmacokinetic Parameter - Plasma Tmax

  Day 1 Time to maximum concentration (Tmax) of ELX-02 plasma concentrations following the subcutaneous (SC) dose on Day 1

  Day 1: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, 36h, 48h, 72h post-dose

• Pharmacokinetic Parameter Plasma - Tmax

  Day 29 Time to maximum concentration (Tmax) of ELX-02 plasma concentrations following the subcutaneous (SC) dose on Day 29

  Day 29: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, 36h, 48h, 72h post-dose

• Pharmacokinetic Parameter - Plasma Rac(AUC24h)

  Accumulation ratio, calculated as AUC24h Day29/AUC24h Day 1

  Day 1 and Day 24 hr

• Pharmacokinetic Parameter - Plasma RAC(Cmax)

  Accumulation ratio, calculated as Cmax Day29/Cmax Day 1

  Day 1 and Day 29

• Urine Pharmacokinetics Parameter - Ae72h

  Day 1 Cumulative amount of unchanged drug excreted into urine (Ae72h) of ELX-02 following the subcutaneous (SC) dose on Day 1

  Day 1: pre-dose and during 0-12h, 12-24h, 24-48h, and 48-72h post-dose

• Urine Pharmacokinetics Parameter - Ae72h

  Day 29 Cumulative amount of unchanged drug excreted into urine (Ae72h) of ELX-02 following the subcutaneous (SC) dose on Day 29

  Day 29: pre-dose and during 0-12h, 12-24h, 24-48h, and 48-72h post-dose

• Urine Pharmacokinetic Parameter - Rmax

  Day 1 Maximum rate of urinary extraction (Rmax) of EXL-02 in each collection time interval following the subcutaneous (SC) dose on Day 1

  Day 1: pre-dose and during 0-12h, 12-24h, 24-48h, and 48-72h post-dose

• Urine Pharmacokinetic Parameter - Rmax

  Day 29 Maximum rate of urinary extraction (Rmax) of ELX-02 in each collection time interval following the subcutaneous (SC) dose on Day 29

  Day 29: pre-dose and during 0-12h, 12-24h, 24-48h, and 48-72h post-dose

• Urine Pharmacokinetics Parameter - Fe12h Day 1

  Percent of dose excreted (Fe) in urine on Day 1

  12 hours

• Urine Pharmacokinetics Parameter - Fe 12h on Day 29

  Percent of dose excreted (Fe) in urine on Day 29

  12 h on Day 29

• Urine Pharmacokinetics Parameter - CLR24h on Day 1

  Renal clearance on Day 1 (CLR=Ae24h/plasmaAUC24h)

  24 hours

• Urine Pharmacokinetics Parameter - CLR24h

  Renal clearance on Day 29 (CLR=Ae24h/plasmaAUC24h)

  24 h

Secondary Outcomes (1)

• Number of Patients Experiencing at Least One Treatment-Emergent Adverse Events (TEAEs)

  Day 1-29

Study Arms (2)

Placebo Comparator Arm

PLACEBO COMPARATOR

Placebo

Drug: Placebo

ELX-02

EXPERIMENTAL

ELX-02

Drug: ELX-02

Interventions

ELX-02 DRUG

ELX-02 is a synthetic, designer eukaryotic ribosomal specific glycoside (ERSG) optimized as a translational read-through drug

ELX-02

Placebo DRUG

Placebo

Placebo Comparator Arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be able and willing to provide written Informed Consent indicating that the subject has been informed of all pertinent aspects of the study.
• Healthy female subjects and male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive.
• Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate measurement, 12-lead electrocardiogram (ECG), and clinical laboratory tests.
• Female subjects of non-childbearing potential must meet at least one of the following criteria:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; post-menopausal status will be confirmed by a serum follicle-stimulating hormone level;
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential and may be enrolled if they have negative pregnancy tests at screening and admission day and agree to use a highly effective method of contraception for 14 days before first study drug administration and 28 days after last study drug administration. Female subjects of childbearing potential must agree to undergo repeated pregnancy tests.
• Male subjects must be willing to use an effective method of contraception. They must agree to use a condom consistently and correctly, during the course of the study until 28 days after last study drug administration.
• Not using any prescription medication and dietary supplements within 30 days or 5 half lives (whichever is longer) prior to the first study drug administration, except for contraceptives - nor be taking any over-the-counter (OTC) herbal or medicinal products. As an exception, acetaminophen/paracetamol may be used at doses of ≤2 g/day.
• Non-smoking and no use of any tobacco or nicotine products (by declaration) for a period of at least 6 months prior to screening visit.
• Be on no medication with potential to impair renal function (e.g., non steroidal anti inflammatory \[NSAID\]s) or with ototoxic potential (e.g., quinine, salicylates, aminoglycosides).
• Normal renal function (glomular filtration rate \>60 mL/min) based on creatinine plasma concentration and the Modification of Diet in Renal Disease (MDRD) equation for estimated glomular filtration rate. Subjects with lower MDRD clearance can be included on the condition that they have a normal 24h creatinine clearance (determined by a 24h urine collection).
• Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) serology tests at screening.
• No history of alcohol or DOA. Negative urine test for DOA and alcohol breath test at screening and Day -1.
• No personal history (or current) or hereditary hearing loss, persistent tinnitus, persistent vertigo, persistent imbalance and persistent unsteadiness.

You may not qualify if:

• Subjects 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 subjects who are the Sponsor employees directly involved in the conduct of the study.
• Concurrent participation or participation in another clinical trial within at least 5 tissue half-lives prior to dosing (calculated from the previous study's last dosing day). If the previous trial involved agents with delayed effects or prolonged metabolism, a 12 months interval is required.
• Evidence or history of clinically relevant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies). This includes any acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
• Presence of mitochondrial mutations making subject susceptible to aminoglycoside toxicity.
• Subjects with any history of ear disease or surgeries, persistent dizziness or persistent tinnitus.
• Subjects with any abnormality at screening, that indicates the presence of a vestibular pathology, conductive hearing loss or balance problem (by an ENT).
• Subjects with abnormalities in audiometry results at screening as follows: any pure-tone threshold \>55 dB and/or inter-ear difference in any frequency of \>20 dB.
• Dizziness Handicap Inventory (DHI)-H score\>16. Tinnitus Handicap Inventory (THI)-H score \>14.
• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening.
• Screening supine BP ≥ 140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), following at least 5 min of supine rest. If BP is ≥ 140 mm Hg (systolic) or ≥ 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.
• Screening supine 12-lead ECG demonstrating QTc \>450 msec for men and \>470 msec for women, or a QRS interval \>120 msec. If QTc or QRS exceed these limits, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
• Subjects with ANY abnormalities in clinical laboratory tests at screening, considered by the study physician as clinically relevant. In particular, subjects with alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine and total bilirubin ≥ 1.5 upper limit of normal will be excluded.
• Pregnant or breastfeeding female subjects.
• Subjects who donated blood or received blood or plasma derivatives in the three months preceding study drug administration.
• Unwilling or unable to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures and the restrictions described in this protocol.

Sponsors & Collaborators

• Eloxx Pharmaceuticals, Inc.: lead
• SGS Life Sciences, a division of SGS Belgium NV: collaborator

Study Sites (1)

SGS Life Sciences, Clinical Pharmacology Unit

Antwerp, Belgium

Location

Related Publications (1)

• Leubitz A, Vanhoutte F, Hu MY, Porter K, Gordon E, Tencer K, Campbell K, Banks K, Haverty T. A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of ELX-02 in Healthy Subjects. Clin Pharmacol Drug Dev. 2021 Aug;10(8):859-869. doi: 10.1002/cpdd.914. Epub 2021 Jan 19.

  PMID: 33465285 RESULT

Related Links

• Eloxx Pharmaceuticals Website

MeSH Terms

Conditions

Genetic Diseases, Inborn

Interventions

ELX-02

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Executive Director Clinical Trials
• Organization: Eloxx Pharmaceuticals

CTI@eloxxpharma.com

1-781-577-5300

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Cohort 1: ELX-02 0.1 mg/kg or placebo SC twice a week for 9 doses; * Cohort 2: ELX-02 0.3 mg/kg or placebo SC twice a week for 9 doses; * Cohort 3: ELX-02 1.0 mg/kg or placebo SC twice a week for 9 doses; * Cohort 4: ELX-02 2.5 mg/kg or placebo SC twice a week for 9 doses; * Cohort 5: ELX-02 up to 2.5 mg/kg (50 mg/mL per injection) or placebo SC twice a week for 9 doses; * Cohort 6: ELX-02 2.5 to 5.0 mg/kg or placebo SC twice a week for 9 doses. Optional Cohort * Cohort 7: ELX-02 up to 5.0 mg/kg or placebo SC twice a week for 9 doses. Optional Cohort

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 13, 2017
• Study Start: October 11, 2017
• Primary Completion: June 17, 2019
• Study Completion: July 17, 2019
• Last Updated: March 16, 2021
• Results First Posted: March 16, 2021

Record last verified: 2021-02

Locations

BE (1)