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IV アミカシンで治療された NTM 患者における耳毒性の予防

2026年9月28日 更新者：Kevin Winthrop

非結核性抗酸菌症の治療のために静脈内アミカシンを投与されている患者における薬物誘発性難聴の予防のための ORC-13661 の有効性と安全性に関する第 2 相試験

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.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

105

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

  • 名前：Violet Tiffee
  • 電話番号：503-494-1433
  • メール：tiffee@ohsu.edu

研究場所

  • アメリカ
    • California
      • San Francisco、California、アメリカ、94143
        • 募集
        • University of California, San Francisco
        • 副調査官：
          • Shoshana Zha, MD, PhD
        • 主任研究者：
          • Catherine DeVoe, MD
        • コンタクト：
    • Colorado
      • Denver、Colorado、アメリカ、80206
        • 募集
        • National Jewish Health
        • 主任研究者：
          • Charles L Daley, MD
        • コンタクト：
        • コンタクト：
    • Maryland
      • Baltimore、Maryland、アメリカ、21224
        • 募集
        • Johns Hopkins University
        • コンタクト：
        • 主任研究者：
          • Elisa Ignatius, MD, MSc
        • コンタクト：
    • Minnesota
      • Rochester、Minnesota、アメリカ、55905
        • 引きこもった
        • Mayo Clinic
    • New York
      • Manhasset、New York、アメリカ、11030
        • 募集
        • Northwell Health
        • 主任研究者：
          • Lisa Hayes, MD
        • 副調査官：
          • Marcia Epstein, MD
        • コンタクト：
        • コンタクト：
    • Oregon
      • Portland、Oregon、アメリカ、97239
        • 募集
        • Oregon Health & Science University
        • 主任研究者：
          • Kevin Winthrop, MD, MPH
        • コンタクト：
        • コンタクト：
    • South Carolina
      • Charleston、South Carolina、アメリカ、29425
        • 募集
        • Medical University of South Carolina
        • 主任研究者：
          • Patrick Flume, MD
        • コンタクト：
        • コンタクト：
    • Texas
      • Tyler、Texas、アメリカ、75708
        • 募集
        • University of Texas Health Science Center
        • コンタクト：
        • 主任研究者：
          • Devanshi Mehta, MD

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～80年 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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).

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：防止
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：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.
薬：ORC-13661

High-dose intervention (30mg daily)

薬：ORC-13661

Low-dose intervention (12mg daily)
実験的：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.
薬：ORC-13661

High-dose intervention (30mg daily)

薬：ORC-13661

Low-dose intervention (12mg daily)
プラセボコンパレーター：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.
薬：Placebo

Placebo intervention

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Mitigation or Prevention of Ototoxicity
時間枠：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.

二次結果の測定

結果測定
メジャーの説明
時間枠
Mitigation or Prevention of hearing impairment with regards to speech perceptions
時間枠：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
時間枠：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
時間枠：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.

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Kevin Winthrop

協力者

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

捜査官

  • 主任研究者：Kevin L Winthrop, MD, MPH、Oregon Health and Science University
  • 主任研究者：Edwin Rubel, PhD、Oricula Therapeutics

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2025年6月2日

一次修了 (推定)

2028年2月29日

研究の完了 (推定)

2028年2月29日

試験登録日

最初に提出

2023年2月7日

QC基準を満たした最初の提出物

2023年2月7日

最初の投稿 (実際)

2023年2月15日

学習記録の更新

投稿された最後の更新 (実際)

2026年10月1日

QC基準を満たした最後の更新が送信されました

2026年9月28日

最終確認日

2026年9月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • SOUNDS Trial
  • U01DC020175 (米国 NIH グラント/契約)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

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