Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)
シスタチオニンβシンターゼ欠損症による古典的ホモシスチン尿症の参加者を対象に、標準治療に加えて皮下投与されるペグチバチナーゼの有効性と安全性を評価する第3相並行群治療、盲検、ランダム化、プラセボ対照試験（HARMONY）
Researchers are looking for a better way to treat people living with classical homocystinuria (HCU), a rare inherited condition. It is caused by changes in the cystathionine beta-synthase (or "CBS") gene and prevents an enzyme from working correctly in the body. This enzyme helps break down homocysteine, which is produced when the body processes methionine from protein-containing foods. This helps keep homocysteine and methionine at healthy levels. When this enzyme is not working, homocysteine and methionine build up in the blood and then spread into different tissues of the body and stop these body tissues from working normally.
People living with HCU can experience problems with their vision, bones, blood vessels, thinking, learning, and memory. Available treatments for HCU include a low-methionine diet (typically achieved by limiting protein-containing foods), a methionine-free protein supplement to help meet daily protein needs, and betaine (Cystadane®). These treatments are either not sufficient or are hard to take for many patients.
Pegtibatinase was designed by researchers to act like the CBS enzyme, which is missing or not working properly in people living with HCU. Researchers are studying whether adding pegtibatinase to standard treatment can lower homocysteine levels.
Researchers want to learn how safe and effective pegtibatinase is, how it moves through and affects the body, and how it may affect the daily lives of people with HCU.
The study plans to enroll participants from the US, Australia, Belgium, France, Germany, Ireland, Italy, Poland, Portugal, Qatar, Saudi Arabia, Spain, Turkey, and the United Kingdom. Many study visits may happen at home, depending on where you live and local regulations. Some visits may include a home nurse and telemedicine appointments with the study doctor.
調査の概要
詳細な説明
Primary Objective:
Researchers want to learn more about how pegtibatinase will affect homocysteine and methionine levels when it is injected under the skin in participants already receiving standard treatment.
Blood tests will be used to measure changes in these levels during the study.
Secondary Objectives:
Researchers also want to learn:
- Is pegtibatinase safe and tolerable (how does it make participants feel)?
- How does pegtibatinase move throughout the body?
- Does pegtibatinase produce antibodies (proteins the body makes that may stop pegtibatinase from working or cause side effects)?
- How does pegtibatinase affect daily lives of participants with HCU? Researchers will use blood tests, urine tests, physical examinations, and questionnaires to answer these questions.
Study Population and Treatments:
This is a global study will include children and adults from 12 to 65 years old. Participants in the study will take their standard of care treatment. Participants will be put into 1 of 2 groups at random (like the flip of a coin) to take either:
- pegtibatinase, or
- an injection that does not have any medicine in it (or "placebo"). These are given as injections under the skin 2 times a week for up to 24 weeks. Neither the researchers nor the participant knows which treatment they are getting until the study is complete.
Study Duration and Visits:
Participants may be in the study for up to 38 weeks, including the screening period of up to 4 weeks, a pre-treatment period of up to 6 weeks where the participants will discuss their current diet with a dietitian (a health professional specialized in nutrition), a blinded treatment period of up to 24 weeks, and a safety follow-up visit completed 4 weeks after the last dose of study medication. Participants who complete the blinded treatment period may qualify to join the ENSEMBLE study before finishing the safety follow-up visit.
Participants who meet all study requirements may have up to 58 study visits. Visits may take place at a study center, at home, or by telemedicine.
These visits can include:
- Blood and urine tests
- Physical examinations
- Questionnaires
- Injections
- Questions about how they are feeling or any problems they are having
Safety / Adverse Events:
Researchers will monitor participants for any medical problems that occur during the study. Participants will have regular laboratory tests, health checkups, and study visits to monitor their health and safety.
Benefit-risk Conclusion:
Researchers have worked to reduce risks to participants in this study. They believe the risks of taking pegtibatinase in this study are justified by the potential benefits that they think pegtibatinase may have for people with HCU.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Travere Call Center
- 電話番号：1-877-659-5518
- メール：medinfo@travere.com
研究場所
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Dublin、アイルランド
- 募集
- Children's Health Ireland (CHI) at Temple Street
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Arizona
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Phoenix、Arizona、アメリカ、85006
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- Phoenix Children's Hospital
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Connecticut
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New Haven、Connecticut、アメリカ、06519
- 募集
- Yale University School of Medicine
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Georgia
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Atlanta、Georgia、アメリカ、30322
- 募集
- Emory University
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Illinois
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Chicago、Illinois、アメリカ、60611
- 募集
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Maine
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Portland、Maine、アメリカ、04102
- 募集
- Maine Health - Maine Medical Center
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Maryland
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Chevy Chase、Maryland、アメリカ、20815
- 募集
- Uncommon Cures
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New York
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New York、New York、アメリカ、10029
- 募集
- The Mount Sinai Hospital
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North Carolina
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Morrisville、North Carolina、アメリカ、27560
- 募集
- Science 37 - Virtual Site
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Oregon
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Portland、Oregon、アメリカ、97239
- まだ募集していません
- Oregon Health and Science University
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
- 募集
- Children's Hospital of Philadelphia
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Pittsburgh、Pennsylvania、アメリカ、15224
- 募集
- University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
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Texas
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Dallas、Texas、アメリカ、75390
- 募集
- University of Texas Southwestern Medical Center
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Utah
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Salt Lake City、Utah、アメリカ、84113
- 募集
- Utah Health - The University of Utah Primary Children's Hospital
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Birmingham、イギリス
- 募集
- Birmingham Women's and Children's NHS Foundation Trust
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Birmingham、イギリス
- 募集
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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London、イギリス
- まだ募集していません
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Salford、イギリス
- 募集
- Salford Royal NHS Foundation Trust - Salford Royal Hospital
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Bari、イタリア
- まだ募集していません
- Ospedale Pediatrico Giovanni XXIII
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Genova、イタリア
- まだ募集していません
- IRCCS Istituto Giannina Gaslini
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Milan、イタリア
- まだ募集していません
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
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Monza、イタリア
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- Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
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Padova、イタリア
- まだ募集していません
- Azienda Ospedaliera di Padova
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Adelaide、オーストラリア
- 募集
- Royal Adelaide Hospital
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Parkville、オーストラリア
- 募集
- Royal Children's Hospital Melbourne
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Westmead、オーストラリア
- 募集
- Westmead Hospital
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Doha、カタール
- 募集
- Hamad General Hospital
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Doha、カタール
- 募集
- Sidra Hospital
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Riyadh、サウジアラビア
- 募集
- King Abdullah International Medical Research Center
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Riyadh、サウジアラビア
- 募集
- King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
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Barcelona、スペイン
- 募集
- Hospital Sant Joan de Déu
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Madrid、スペイン
- 募集
- Hospital Universitario 12 de Octubre
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Madrid、スペイン
- 募集
- Hospital Universitario Ramón y Cajal
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Santiago de Compostela、スペイン
- 募集
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Seville、スペイン
- 募集
- Hospital Universitario Virgen del Rocío
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Ankara、トルコ（Türkiye）
- 募集
- Gazi University Hospital
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Bornova、トルコ（Türkiye）
- まだ募集していません
- Ege Üniversitesi Hastanesi Bornova
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Istanbul、トルコ（Türkiye）
- まだ募集していません
- Istanbul University Cerrahpasa Hospital
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Hamburg、ドイツ
- まだ募集していません
- Universitätsklinikum Hamburg-Eppendorf
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Leipzig、ドイツ
- まだ募集していません
- Universitätsklinikum Leipzig
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Münster、ドイツ
- まだ募集していません
- Universitätsklinikum Münster
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Paris、フランス
- 募集
- Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
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Tours、フランス
- 募集
- CHRU Hôpitaux de Tours - Hôpital Bretonneau
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Vandœuvre-lès-Nancy、フランス
- 募集
- Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
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Brussels、ベルギー
- 募集
- Cliniques Universitaires Saint-Luc
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Edegem、ベルギー
- 募集
- Universitair Ziekenhuis Antwerpen (UZA)
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Coimbra、ポルトガル
- 募集
- Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
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Lisbon、ポルトガル
- 募集
- Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
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Porto、ポルトガル
- まだ募集していません
- Unidade Local de Saúde de São João, EPE - Hospital São João
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Krakow、ポーランド
- まだ募集していません
- SP ZOZ Szpital Uniwersytecki w Krakowie
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Warsaw、ポーランド
- 募集
- Instytut Pomnik-Centrum Zdrowia Dziecka
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Warsaw、ポーランド
- まだ募集していません
- Instytut Matki i Dziecka
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Must be ≥12 to ≤65 years of age, at the time of signing the informed consent
- Must have a diagnosis of classical HCU based on clinical, biochemical, and/or molecular genetic testing
- Plasma tHcy ≥80 µM at Screening visit, with allowance for up to 18 participants who may be enrolled with a Screening plasma tHcy ≥50 to <80 µM
- Participants who can become pregnant must have a negative pregnancy test before starting the study and must use a highly effective form of birth control (less than 1% risk of pregnancy per year) during the study and for at least 4 weeks after the last dose.
- Willing to maintain a generally stable diet for the duration of the study (unless changes are required based on medical/safety reasons)
- Willing to maintain generally stable intake and doses of betaine, pyridoxine, and medical food for the duration of the study (unless changes are required based on medical/safety reasons)
Exclusion Criteria:
- Diagnosis of Marfan syndrome, methylenetetrahydrofolate reductase (MTHFR) deficiency, or disorder of cobalamin metabolism
- Concurrent disease or condition (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease) that would interfere with study participation or safety (excluding complications of HCU).
- History of major thrombotic event (eg, cerebrovascular accident, myocardial infarction, pulmonary embolism) in the previous 6 months.
- Body weight ≥160 kg.
- Use or planned use of any injectable drugs containing PEG (excluding PEG-containing vaccines)
- Any previous exposure to pegtibatinase and/or previous participation in a clinical study that included administration of pegtibatinase or pegtarviliase
- Prior severe immune reaction to a PEG-containing product
研究計画
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：処理
- 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 |
|---|---|
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プラセボコンパレーター：プラセボ
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volume-matched saline SC BIW |
|
実験的：ペグチバチナーゼ
|
Pegtibatinase BIW
他の名前：
|
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 |
|---|---|---|
|
Change from baseline in plasma tHcy levels - Weeks 6 to 12
時間枠：Weeks 6 - 12
|
Change between baseline and average of 6 to 12 week (6, 8, 10, and 12 week) plasma tHcy levels in participants receiving pegtibatinase vs. placebo. Baseline tHcy level defined as average of Week -3, Week -1, and Day 1 pre-dose plasma tHcy |
Weeks 6 - 12
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change from baseline in plasma tHcy levels - Weeks 16 to 24
時間枠：Weeks 16 - 24
|
Change between baseline and average of 16 to 24 week (16, 20, and 24 week) plasma tHcy levels in participants receiving pegtibatinase vs. placebo. Baseline tHcy level defined as average of Week -3, Week -1, and Day 1 pre-dose plasma tHcy |
Weeks 16 - 24
|
協力者と研究者
捜査官
- スタディディレクター：Michael Imperiale, MD、Travere Therapeutics, Inc.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
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
- TVTX-TVT058-301
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?
IPD プランの説明
Requests for clinical trial data, including language stating its intended use, should be directed to datarequest@travere.com. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.
IPD 共有時間枠
Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication.
IPD 共有アクセス基準
Requires submission and approval of intended use and a data sharing agreement.
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米国FDA規制医薬品の研究
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