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Forebygging av ototoksisitet hos NTM-pasienter behandlet med IV Amikacin

28. september 2026 oppdatert av: Kevin Winthrop

Fase 2-studie av effektiviteten og sikkerheten til ORC-13661 for forebygging av legemiddelindusert hørselstap hos pasienter som får intravenøs amikacin for behandling av ikke-tuberkuløs mykobakteriesykdom

The goal of this clinical trial is to test the effectiveness of the study drug, ORC-13361, in preventing hearing loss in patients with NTM infection who are undergoing treatment with IV amikacin therapy. The main question this study aims to answer is:

  • Is ORC-13661 effective for preventing or lessening hearing loss induced by amikacin treatment?
  • Is ORC-13661 effective for preventing or lessening other measures of hearing impairment?

Participants will be asked to take a study drug while they are being treated with IV amikacin. Participants will take study drug for 90 days or until the end of their amikacin treatment, whichever comes first. During this time, researchers will gather clinical data on the participants' health.

Researchers will compare three groups - two groups taking different doses of the study drug and one group taking a placebo drug - to see if dose of drug has any effect on preventing hearing loss. A placebo is a look-alike substance that contains no active drug.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Nontuberculous mycobacteria (NTM) are environmental bacteria that can cause chronic, debilitating pulmonary disease, primarily affecting those over age 60. In more severe cases of NTM infection, patients are given a therapy with parenteral aminoglycoside antibiotics (AGs), to achieve control or cure. Amikacin is the most commonly used aminoglycoside for treatment in this setting, however it is limited by in its use by its tendency to cause ototoxicity including hearing loss and/or vestibular dysfunction. Ototoxicity refers to substances (i.e. medications) which are damaging to the inner ear sensory cells and may result in functional hearing loss and other negative effects.

This main goal of this study is to test the effectiveness of the study drug, ORC-13661, a small molecule compound being developed as an adjunct therapy to be administered during AG use in order to prevent associated ototoxicity. This study is a randomized, double-blind, placebo-controlled, multicenter, dose-ranging clinical trial to compare the effects and safety of ORC-13661 in preventing or mitigating hearing in patients taking amikacin.

105 participants will be enrolled across 5 enrolling sites over the course of the study. Participants will be randomized in equal numbers between three different study arms: high-dose ORC-13661, low-dose ORC-13661, and placebo. Participants will take study drug for 90 days from the start of their amikacin treatment or until their amikacin treatment ends, whichever comes first.

The primary outcome of this study is prevention or mitigation of amikacin-induced ototoxicity. Secondary outcomes include changes in speech perception, auditory and balance effects, and quality of hearing.

Studietype

Intervensjonell

Registrering (Antatt)

105

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Forente stater
    • California
      • San Francisco, California, Forente stater, 94143
        • Rekruttering
        • University of California, San Francisco
        • Underetterforsker:
          • Shoshana Zha, MD, PhD
        • Hovedetterforsker:
          • Catherine DeVoe, MD
        • Ta kontakt med:
    • Colorado
      • Denver, Colorado, Forente stater, 80206
        • Rekruttering
        • National Jewish Health
        • Hovedetterforsker:
          • Charles L Daley, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • Maryland
      • Baltimore, Maryland, Forente stater, 21224
        • Rekruttering
        • Johns Hopkins University
        • Ta kontakt med:
        • Hovedetterforsker:
          • Elisa Ignatius, MD, MSc
        • Ta kontakt med:
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55905
        • Tilbaketrukket
        • Mayo Clinic
    • New York
      • Manhasset, New York, Forente stater, 11030
        • Rekruttering
        • Northwell Health
        • Hovedetterforsker:
          • Lisa Hayes, MD
        • Underetterforsker:
          • Marcia Epstein, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • Oregon
      • Portland, Oregon, Forente stater, 97239
        • Rekruttering
        • Oregon Health & Science University
        • Hovedetterforsker:
          • Kevin Winthrop, MD, MPH
        • Ta kontakt med:
        • Ta kontakt med:
    • South Carolina
      • Charleston, South Carolina, Forente stater, 29425
        • Rekruttering
        • Medical University of South Carolina
        • Hovedetterforsker:
          • Patrick Flume, MD
        • Ta kontakt med:
        • Ta kontakt med:
    • Texas
      • Tyler, Texas, Forente stater, 75708
        • Rekruttering
        • University of Texas Health Science Center
        • Ta kontakt med:
        • Hovedetterforsker:
          • Devanshi Mehta, MD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Providing informed consent, documented by signing and dating the currently valid informed consent form.
  2. Considered by the Investigator to have unimpaired consent capacity, without reliance on a legally authorized representative.
  3. Stated willingness and ability to comply with study procedures and availability for the duration of the study.
  4. Aged > 18 and < 80.
  5. NTM infection meeting current Pulmonary NTM guidelines from the American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA) for systemic (IV) aminoglycoside therapy.
  6. Anticipated duration of IV amikacin treatment of at least 30 days at time of study entry.
  7. Statement of ability to take oral medication and adhere to the daily dosing regimen.
  8. For females of reproductive potential: If they are of childbearing potential, they must agree in writing to practice an effective double barrier method of contraception from the signing of the informed consent form until 1 month following discontinuation of study drug treatment or agree to practice true abstinence, when this is consistent with the preferred and usual lifestyle of the subject.
  9. For males of reproductive potential: Agree to practice effective barrier contraception from the signing of the informed consent form until 3 months (one spermatogenesis cycle) following the last dose of study drug or agree to practice true abstinence.

Exclusion Criteria:

  1. Received a systemic aminoglycoside antibiotic within 6 months prior to planned first dose of amikacin.
  2. ECG at Screening or prior to randomization (mean of triplicate values) with QT interval corrected using Fridericia's formula (QTcF interval) ≥ 450 msec.
  3. ECG at Screening or prior to randomization with abnormalities that, in the Investigator's judgment, might predispose patient to clinically significant arrhythmia.
  4. Patients taking strong CYP3A4 inducers such as rifampin and rifabutin in the 7 days prior to randomization or have the need for ongoing treatment with concomitant oral or intravenous therapy with strong CYP3A4 inducers during the study. If an additional antibiotic is needed, then azithromycin will be used.
  5. Patients taking strong CYP3A4 inhibitors such as clarithromycin in the 7 days prior to randomization or the need for ongoing treatment with concomitant oral or intravenous therapy with strong CYP3A4 inhibitors during the study. If an additional antibiotic is needed, then azithromycin will be used.
  6. Patients taking clofazimine or bedaquiline AND who also have congestive heart failure, significant ventricular arrhythmia, uncorrected hypokalemia, or ECG (single at Screening, mean of triplicate prior to randomization) showing QRS > 120 msec or heart rate < 50 bpm.
  7. Patients with amikacin exposure within the 6 months prior to randomization.
  8. Patients with known amikacin resistance (MIC >64)
  9. Progressive liver disease (Child-Pugh B or C) which would affect or invalidate interpretation of change from the baseline liver function tests over the course of the study.
  10. Signs of disturbed integrity of the tympanic membrane, determined by otoscopy or tympanometry, including chronic perforation or middle ear or ear canal inflammation or effusion.
  11. History of congenital hearing loss, otological surgery (excluding myringotomy tubes or simple tympanoplasty healed and currently intact), sudden hearing loss, or Meniere's disease.
  12. Bilateral profound hearing loss (>90 Decibels [dB] HL) at all test frequencies.
  13. Conductive hearing loss evidenced by average air-bone-gaps >15 dB HL for 0.25-4.0 kilohertz (kHz)
  14. History of active malignancy, either untreated or under active treatment.
  15. History of risk factors for Torsades des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  16. Venous access not adequate for performance of study procedures.
  17. Presence of any circumstance, condition, ECG or laboratory finding that, based on investigator judgment, would interfere with study procedures or assessments or present to the patient an unreasonable risk from participation in this study.
  18. Current or anticipated use of excluded concomitant medications as specified in Section 6.5.
  19. Pregnant or lactating.
  20. Female of childbearing potential who does not have a negative serum pregnancy test and does not agree in writing to using a double barrier method of contraception.
  21. Female relying on menopausal status for contraception who does not have Follicle-Stimulating Hormone (FSH) level consistent with that condition and who does not agree in writing to using a double barrier method of contraception.
  22. Currently under correctional supervision (imprisoned, on probation or parole).

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: High Dose ORC-13661

This arm is a daily treatment regimen of study drug (ORC-13661) with a loading dose of 150mg followed by a daily dose of 30mg. Treatment regimen will run concurrently with treatment with IV amikacin. Study drug treatment will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.
Legemiddel: ORC-13661

High-dose intervention (30mg daily)

Legemiddel: ORC-13661

Low-dose intervention (12mg daily)
Eksperimentell: Low Dose ORC-13661

This arm is a daily treatment regimen of study drug (ORC-13661) with a loading dose of 60mg capsules followed by a daily dose of 12mg capsules. Treatment regimen will run concurrently with treatment with IV amikacin. Study drug treatment will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.
Legemiddel: ORC-13661

High-dose intervention (30mg daily)

Legemiddel: ORC-13661

Low-dose intervention (12mg daily)
Placebo komparator: Placebo

This arm is a daily treatment regimen of a placebo with a loading dose and a daily dose of placebo capsules to match the treatment arms. Placebo regimen will run concurrently with treatment with IV amikacin. Placebo regimen will continue until treatment with IV amikacin ends or 90 days, whichever is earlier.
Legemiddel: Placebo

Placebo intervention

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Mitigation or Prevention of Ototoxicity
Tidsramme: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Outcome is measured by changes from baseline using the American Speech-Language-Hearing Association (ASHA) shift criterion in patients with NTM disease undergoing treatment with IV amikacin therapy
Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Mitigation or Prevention of hearing impairment with regards to speech perceptions
Tidsramme: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Outcome is measured by changes to patient's speech perceptions using the High Frequency Digits-in-Noise (HF-DIN) test
Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.
Mitigation or Prevention of hearing impairment with regards to perceived auditory and balance effects
Tidsramme: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Outcome is measured by changes to patient's tinnitus using the Modified-Tinnitus Ototoxicity Monitoring Interview (TOMI)
Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.
Mitigation or Prevention of hearing impairment with regards to speech, spatial and quality of hearing
Tidsramme: Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Outcome is measured by changes to patient's Speech, Spatial and Quality of Hearing Scale (SSQ12)
Baseline to 28 (±5) days after study treatment discontinuation or 28 days after 90 days of study treatment, whichever comes first.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Kevin Winthrop

Samarbeidspartnere

Medical University of South Carolina
Johns Hopkins University
Mayo Clinic
Northwell Health
University of Washington
University of California, San Francisco
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Center for Advancing Translational Sciences (NCATS)
The University of Texas Health Science Center at Tyler
National Jewish Health
Oricula Therapeutics

Etterforskere

  • Hovedetterforsker: Kevin L Winthrop, MD, MPH, Oregon Health and Science University
  • Hovedetterforsker: Edwin Rubel, PhD, Oricula Therapeutics

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

2. juni 2025

Primær fullføring (Antatt)

29. februar 2028

Studiet fullført (Antatt)

29. februar 2028

Datoer for studieregistrering

Først innsendt

7. februar 2023

Først innsendt som oppfylte QC-kriteriene

7. februar 2023

Først lagt ut (Faktiske)

15. februar 2023

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

1. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

28. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • SOUNDS Trial
  • U01DC020175 (U.S. NIH-stipend/kontrakt)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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