Pegtibatinase as a Treatment for Participants With Classical Homocystinuria (HCU) Receiving Standard of Care Treatment (HARMONY)
시스타티오닌 베타 신타제 결핍으로 인한 고전적 호모시스틴뇨증(HARMONY) 참가자의 표준 치료 외에 피하 투여되는 페그티바티나제의 효능과 안전성을 평가하기 위한 제3상 병렬군 치료, 맹검, 무작위, 위약 대조 연구(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.
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 3단계
연락처 및 위치
연구 연락처
- 이름: Travere Call Center
- 전화번호: 1-877-659-5518
- 이메일: medinfo@travere.com
연구 장소
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Hamburg, 독일
- 아직 모집하지 않음
- Universitätsklinikum Hamburg-Eppendorf
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Leipzig, 독일
- 아직 모집하지 않음
- Universitätsklinikum Leipzig
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Münster, 독일
- 아직 모집하지 않음
- Universitätsklinikum Münster
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Arizona
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Phoenix, Arizona, 미국, 85006
- 모병
- Phoenix Children's Hospital
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Connecticut
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New Haven, Connecticut, 미국, 06519
- 모병
- Yale University School of Medicine
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Georgia
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Atlanta, Georgia, 미국, 30322
- 모병
- Emory University
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Illinois
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Chicago, Illinois, 미국, 60611
- 모병
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Maine
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Portland, Maine, 미국, 04102
- 모병
- Maine Health - Maine Medical Center
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Maryland
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Chevy Chase, Maryland, 미국, 20815
- 모병
- Uncommon Cures
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New York
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New York, New York, 미국, 10029
- 모병
- The Mount Sinai Hospital
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North Carolina
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Morrisville, North Carolina, 미국, 27560
- 모병
- Science 37 - Virtual Site
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Oregon
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Portland, Oregon, 미국, 97239
- 아직 모집하지 않음
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104
- 모병
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, 미국, 15224
- 모병
- University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
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Texas
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Dallas, Texas, 미국, 75390
- 모병
- University of Texas Southwestern Medical Center
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Utah
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Salt Lake City, Utah, 미국, 84113
- 모병
- Utah Health - The University of Utah Primary Children's Hospital
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Brussels, 벨기에
- 모병
- Cliniques Universitaires Saint-Luc
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Edegem, 벨기에
- 모병
- Universitair Ziekenhuis Antwerpen (UZA)
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Riyadh, 사우디 아라비아
- 모병
- King Abdullah International Medical Research Center
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Riyadh, 사우디 아라비아
- 모병
- King Faisal Specialist Hospital and Research Centre (KFSHRC) - Riyadh
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Barcelona, 스페인
- 모병
- Hospital Sant Joan de Déu
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Madrid, 스페인
- 모병
- Hospital Universitario 12 de Octubre
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Madrid, 스페인
- 모병
- Hospital Universitario Ramón y Cajal
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Santiago de Compostela, 스페인
- 모병
- Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
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Seville, 스페인
- 모병
- Hospital Universitario Virgen del Rocío
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Dublin, 아일랜드
- 모병
- Children's Health Ireland (CHI) at Temple Street
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Birmingham, 영국
- 모병
- Birmingham Women's and Children's NHS Foundation Trust
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Birmingham, 영국
- 모병
- University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
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London, 영국
- 아직 모집하지 않음
- University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
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Salford, 영국
- 모병
- Salford Royal NHS Foundation Trust - Salford Royal Hospital
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Bari, 이탈리아
- 아직 모집하지 않음
- Ospedale Pediatrico Giovanni XXIII
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Genova, 이탈리아
- 아직 모집하지 않음
- IRCCS Istituto Giannina Gaslini
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Milan, 이탈리아
- 아직 모집하지 않음
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Policlinico di Milano)
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Monza, 이탈리아
- 아직 모집하지 않음
- Fondazione IRCCS San Gerardo Dei Tintori - Ospedale San Gerardo
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Padova, 이탈리아
- 아직 모집하지 않음
- Azienda Ospedaliera di Padova
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Doha, 카타르
- 모병
- Hamad General Hospital
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Doha, 카타르
- 모병
- Sidra Hospital
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Ankara, 터키 (Türkiye)
- 모병
- Gazi University Hospital
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Bornova, 터키 (Türkiye)
- 아직 모집하지 않음
- Ege Üniversitesi Hastanesi Bornova
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Istanbul, 터키 (Türkiye)
- 아직 모집하지 않음
- Istanbul University Cerrahpasa Hospital
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Coimbra, 포르투갈
- 모병
- Unidade Local de Saúde de Coimbra, EPE - Hospitais da Universidade de Coimbra
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Lisbon, 포르투갈
- 모병
- Unidade Local de Saúde de Santa Maria, EPE - Hospital de Santa Maria
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Porto, 포르투갈
- 아직 모집하지 않음
- Unidade Local de Saúde de São João, EPE - Hospital São João
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Krakow, 폴란드
- 아직 모집하지 않음
- SP ZOZ Szpital Uniwersytecki w Krakowie
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Warsaw, 폴란드
- 모병
- Instytut Pomnik-Centrum Zdrowia Dziecka
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Warsaw, 폴란드
- 아직 모집하지 않음
- Instytut Matki i Dziecka
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Paris, 프랑스
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- Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
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Tours, 프랑스
- 모병
- CHRU Hôpitaux de Tours - Hôpital Bretonneau
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Vandœuvre-lès-Nancy, 프랑스
- 모병
- Centre Hospitalier Régional Universitaire de Nancy (CHRU) - Hopitaux de Brabois - Hôpital d'enfants
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Adelaide, 호주
- 모병
- Royal Adelaide Hospital
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Parkville, 호주
- 모병
- Royal Children's Hospital Melbourne
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Westmead, 호주
- 모병
- Westmead Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
위약 비교기: 위약
|
volume-matched saline SC BIW |
|
실험적: 페그티바티나제
|
Pegtibatinase BIW
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change from baseline in plasma tHcy levels - Weeks 6 to 12
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change from baseline in plasma tHcy levels - Weeks 16 to 24
기간: 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
|
공동 작업자 및 조사자
수사관
- 연구 책임자: Michael Imperiale, MD, Travere Therapeutics, Inc.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- TVTX-TVT058-301
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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 공유 기간
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 공유 액세스 기준
Requires submission and approval of intended use and a data sharing agreement.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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