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Prevenzione dell'ototossicità nei pazienti con NTM trattati con amikacina IV

28 settembre 2026 aggiornato da: Kevin Winthrop

Studio di fase 2 sull'efficacia e la sicurezza di ORC-13661 per la prevenzione della perdita dell'udito indotta da farmaci in pazienti che ricevono amikacina per via endovenosa per il trattamento della malattia da micobatterio non tubercolare

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

105

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

  • Nome: Violet Tiffee
  • Numero di telefono: 503-494-1433
  • Email: tiffee@ohsu.edu

Luoghi di studio

  • Stati Uniti
    • California
      • San Francisco, California, Stati Uniti, 94143
        • Reclutamento
        • University of California, San Francisco
        • Sub-investigatore:
          • Shoshana Zha, MD, PhD
        • Investigatore principale:
          • Catherine DeVoe, MD
        • Contatto:
    • Colorado
      • Denver, Colorado, Stati Uniti, 80206
        • Reclutamento
        • National Jewish Health
        • Investigatore principale:
          • Charles L Daley, MD
        • Contatto:
        • Contatto:
    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21224
        • Reclutamento
        • Johns Hopkins University
        • Contatto:
        • Investigatore principale:
          • Elisa Ignatius, MD, MSc
        • Contatto:
    • Minnesota
      • Rochester, Minnesota, Stati Uniti, 55905
        • Ritirato
        • Mayo Clinic
    • New York
      • Manhasset, New York, Stati Uniti, 11030
        • Reclutamento
        • Northwell Health
        • Investigatore principale:
          • Lisa Hayes, MD
        • Sub-investigatore:
          • Marcia Epstein, MD
        • Contatto:
        • Contatto:
    • Oregon
      • Portland, Oregon, Stati Uniti, 97239
        • Reclutamento
        • Oregon Health & Science University
        • Investigatore principale:
          • Kevin Winthrop, MD, MPH
        • Contatto:
        • Contatto:
    • South Carolina
      • Charleston, South Carolina, Stati Uniti, 29425
        • Reclutamento
        • Medical University of South Carolina
        • Investigatore principale:
          • Patrick Flume, MD
        • Contatto:
        • Contatto:
    • Texas
      • Tyler, Texas, Stati Uniti, 75708
        • Reclutamento
        • University of Texas Health Science Center
        • Contatto:
        • Investigatore principale:
          • Devanshi Mehta, MD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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).

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Prevenzione
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: ORC-13661

High-dose intervention (30mg daily)

Droga: ORC-13661

Low-dose intervention (12mg daily)
Sperimentale: 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.
Droga: ORC-13661

High-dose intervention (30mg daily)

Droga: ORC-13661

Low-dose intervention (12mg daily)
Comparatore placebo: 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.
Droga: Placebo

Placebo intervention

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Mitigation or Prevention of Ototoxicity
Lasso di tempo: 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.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Mitigation or Prevention of hearing impairment with regards to speech perceptions
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Kevin Winthrop

Collaboratori

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

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

2 giugno 2025

Completamento primario (Stimato)

29 febbraio 2028

Completamento dello studio (Stimato)

29 febbraio 2028

Date di iscrizione allo studio

Primo inviato

7 febbraio 2023

Primo inviato che soddisfa i criteri di controllo qualità

7 febbraio 2023

Primo Inserito (Effettivo)

15 febbraio 2023

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

1 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

28 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • SOUNDS Trial
  • U01DC020175 (Sovvenzione/contratto NIH degli Stati Uniti)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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