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Genetic DiseasePhase 1NCT03309605

Phase 1 Study of ELX-02 in Healthy Adult Subjects

A Phase 1 study testing ELX-02 in people with Genetic Disease and Nonsense Mutation, run by Eloxx Pharmaceuticals, Inc. at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase 1 Multiple Ascending Dose Study in Normal Healthy Volunteers Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Genetic Disease, Nonsense Mutation
What is being tested?
ELX-02
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
62 participants
Where
1 siteBelgium
Study dates
11 Oct 2017to 17 Jul 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

  1. Be able and willing to provide written Informed Consent indicating that the subject has been informed of all pertinent aspects of the study.
  2. 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.
  3. 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.
  1. 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.
  2. 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.
  3. 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.
  4. 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).
  5. 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).
  6. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) serology tests at screening.
  7. No history of alcohol or DOA. Negative urine test for DOA and alcohol breath test at screening and Day -1.
  8. No personal history (or current) or hereditary hearing loss, persistent tinnitus, persistent vertigo, persistent imbalance and persistent unsteadiness.
  9. Body Mass Index (BMI) of 19.0 to 30.0 kg/m2 (inclusive); and a total body weight >50.0 kg (110 lbs) and <100.0 kg.

Exclusion criteria: Subjects with any of the following characteristics/conditions will not be included in the study:

  1. 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.
  2. 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.
  3. 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.
  4. Presence of mitochondrial mutations making subject susceptible to aminoglycoside toxicity.
  5. Subjects with any history of ear disease or surgeries, persistent dizziness or persistent tinnitus.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Pregnant or breastfeeding female subjects.
  12. Subjects who donated blood or received blood or plasma derivatives in the three months preceding study drug administration.
  13. Unwilling or unable to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures and the restrictions described in this protocol.
  14. Known relevant allergy to any drug and/or aminoglycosides.
  15. Subjects with an inability to communicate well with the Investigators and CPU staff (e.g., language problem, poor mental development).
  16. Subjects with visual impairment or inability to read and comprehend the DHI and THI scales.
  17. Subjects with any acute medical situation (e.g., acute infection) within 48 hours of study start, which is considered of significance by the Investigator.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • SGS Life Sciences, Clinical Pharmacology Unit

    Antwerp

Other trials in Belgium

About this study

Official title: A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Third Party Open, Multiple Dose Escalation, Single Center Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Subcutaneously Administered ELX-02 in Independent Consecutive Cohorts of Healthy Subjects

Phase 1 Multiple Ascending Dose Study in Normal Healthy Volunteers

Read the detailed description

This is a study in humans of ELX-02, an advanced synthetic aminoglycoside optimized as a translational read-through drug (TRID) for the treatment of genetic conditions caused by nonsense mutations. This is a classical Phase 1b study designed as a randomized, double-blinded, placebo-controlled, multiple dose escalation to evaluate the safety, tolerability, and pharmacokinetics of ELX-02 in healthy adult volunteers.

Being tested
ELX-02, Placebo
Keywords
Translational read through
Medical subject headings
Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ELX-02Drug

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

  • PlaceboDrug

    Placebo

Study groups in NCT03309605
Study groupRoleWhat they receive
Placebo Comparator ArmPlacebo comparatorPlacebo
Receives: Drug: Placebo
ELX-02ExperimentalELX-02
Receives: Drug: ELX-02

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

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

  3. 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

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

  4. 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

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

  5. 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

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

  6. 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

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

  7. Pharmacokinetic Parameter - Plasma Tmax

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

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

  8. Pharmacokinetic Parameter Plasma - Tmax

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

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

  9. Pharmacokinetic Parameter - Plasma Rac(AUC24h)

    Accumulation ratio, calculated as AUC24h Day29/AUC24h Day 1

    Measured: Day 1 and Day 24 hr

  10. Pharmacokinetic Parameter - Plasma RAC(Cmax)

    Accumulation ratio, calculated as Cmax Day29/Cmax Day 1

    Measured: Day 1 and Day 29

  11. 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

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

  12. 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

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

  13. 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

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

  14. 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

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

  15. Urine Pharmacokinetics Parameter - Fe12h Day 1

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

    Measured: 12 hours

  16. Urine Pharmacokinetics Parameter - Fe 12h on Day 29

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

    Measured: 12 h on Day 29

  17. Urine Pharmacokinetics Parameter - CLR24h on Day 1

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

    Measured: 24 hours

  18. Urine Pharmacokinetics Parameter - CLR24h

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

    Measured: 24 h

Secondary outcomes (1)

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

    TEAEs are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the study treatment

    Measured: Day 1-29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2017
  2. Study start11 Oct 2017
  3. Primary completion17 Jun 2019
  4. Study completion17 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
* 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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03309605
Sponsor's protocol ID
EL-002
Status last verified
Feb 2021
First submitted
10 Oct 2017
Last updated
16 Mar 2021
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 33465285

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ELX-02 in people with Genetic Disease and Nonsense Mutation, run by Eloxx Pharmaceuticals, Inc. at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic Parameters - Plasma AUC0-24 (time frame: Day 1: pre-dose, 15 min, 30 min, 45 min, 1h, 3h, 6h, 12h, 24h, post-dose). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03309605, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2021.

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