적응형 뎅기열 항바이러스 플랫폼 시험 (ADAPT)
적응형 뎅기열 항바이러스 플랫폼 시험(ADAPT): 초기 증상이 있는 뎅기열 환자의 항바이러스 선별을 위한 제2상 무작위, 적응형, 공개 라벨 시험
This is a randomized, open-label adaptive platform trial aiming to screen the antiviral effectiveness of the experimental drug(s) in early dengue infection
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Primary objectives:
- To determine the antiviral effectiveness of the experimental drug(s) in early dengue infection
- To assess the safety and tolerability of the experimental drug(s) in dengue patients
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Secondary objective:
- To assess the effect of the experimental drug(s) in dengue patients on physiological, clinical and virological parameters
연구 개요
상태
상세 설명
This is a randomized, open-label adaptive platform trial investigating the antiviral effectiveness of various intervention arms in patients with lab-confirmed dengue and less than 48 hours of fever. The antiviral candidates in this trial will include the repurposed antiviral drugs, novel small molecule drugs and dengue monoclonal antibody. Patients will be randomly allocated between available treatment arms and compared to standard of care ("no study drug": no placebos will be made for this trial).
The current sites include Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam and Universiti Malaya Medical Centre, Kuala Lumpur, Malaysia. Local ethical approvals have been released. Other sites and countries may be added in due course.
This is a continually running adaptive platform trial, which begins with initial candidate drugs (a total of 4 arms): molnupiravir, remdesivir and VIS513 (a dengue monoclonal antibody). New therapies may be added and poorly performing arms or interventions meeting pre-specific thresholds for in vivo antiviral efficacy will be removed.
The sample size is adaptive with multiple planned interim analyses. The number of patients recruited depends on the results. For each intervention studied the sample size will be adaptive and determined by pre-specified stopping rules for futility and efficacy. Patients are invited to participate in the trial if they present at the healthcare settings with early symptomatic dengue virus infection (less than 48 hours since the onset of fever and positive NS1 antigen test) and can be able to return for follow up visits at 30 and 60 days after randomization.
The randomization ratios will be uniform for all available and eligible arms (1:1:1...).
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Sophie Yacoub, MD., PhD.
- 전화번호: +84 77728736
- 이메일: syacoub@oucru.org
연구 연락처 백업
- 이름: Clinical Trials Unit Oxford University Clinical Research Unit
- 전화번호: +84 28 3924 1983
- 이메일: CTU-Ethics@oucru.org
연구 장소
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Kuala Lumpur, 말레이시아, 59100
- 아직 모집하지 않음
- Universiti Malaya Medical Centre
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연락하다:
- Hang Cheng Ong, Doctor
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Ho Chi Minh City, 베트남, 700000
- 모병
- Hospital for Tropical Diseases, Ho Chi Minh city
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연락하다:
- Lan TH Nguyen, Doctor
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수석 연구원:
- Lan TH Nguyen, Doctor
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부수사관:
- Trieu T Huynh, Doctor
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부수사관:
- Tho V Phan, Doctor
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부수사관:
- Huy X Vo, Doctor
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부수사관:
- Huong TC Nguyen, Doctor
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부수사관:
- Phong T Nguyen, Doctor
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부수사관:
- Vien TD Tran, Doctor
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부수사관:
- Men TH Pham, Doctor
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부수사관:
- Quy T Vo, Doctor
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Female or male patients with a clinical diagnosis of dengue virus infection and less than 48 hours of fever
- Positive NS1 rapid diagnostic test
- >= 10 years or ≥ 18 years of age (depending on license of therapeutic being evaluated)
- Patient is able to give written informed consent or assent for full participation in the study.
- Agreement to stay in hospital for duration of the intervention (most will be 5 days) and follow-up visits at day 30 and 60 post enrolment.
Exclusion Criteria:
- Meets criteria for severe dengue at baseline (severe plasma leakage leading to dengue shock syndrome, fluid accumulation with respiratory distress, severe bleeding, severe organ involvement - AST/ALT>1000 U/L, impaired consciousness, multiple organ dysfunction)
- Pregnancy (either clinically confirmed or by urine dipstick for human chorionic gonadotrophin hormone)
- Breastfeeding women
- Localising features suggesting an alternative/additional diagnosis, e.g. pneumonia, sepsis
- Renal failure (baseline eGFR < 30ml/min)
- History or presence of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, autoimmune, dermatologic or immunosuppressive disorders
- History of allergic disease, allergic reactions or known hypersensitivity to any component of the study product (Mild non-medication allergies allowed)
- Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the participant
- Participation or planned participation in a study involving the administration of an investigational compound within the past one month.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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간섭 없음: Standard of care (arm A)
Patients, who are randomly allocated into arm A will receive the standard of care (no study drug) |
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실험적: Molnupiravir (arm B)
Patients, who are randomly allocated into arm B, will receive 800mg po bid of Molnupiravir for 5 days |
This is an antiviral drug (an RNA dependent RNA polymerase inhibitor, with broad spectrum antiviral activity) currently approved for use in treatment for COVID-19 patients. In this trial, its antiviral effectiveness on the early phase of dengue virus infection will be assessed.
다른 이름들:
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실험적: Monoclonal antibody (arm C)
Patients, who are randomly allocated into arm C, will receive a single dose of 6mg/Kg of the dengue monoclonal antibody via an intravenous line over 2 hours. |
VIS513 is an engineered humanised monoclonal antibody produced by recombinant DNA technology in a mammalian cell (i.e. Chinese hamster ovary) line. It was discovered in the USA by Visterra Inc and subsequently technology for manufacturing and further development was transferred to Serum Institute of India Pvt. Ltd., Pune, India. It has shown potent, specific neutralization of all four serotypes of DENV.
다른 이름들:
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실험적: Remdesivir (arm D)
Patients, who are randomly allocated into arm D, will receive:
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Remdesivir (GS-443902) is a nucleoside analogue - RNA dependent RNA polymerase inhibitor.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Viral clearance rate
기간: From randomization until day 5 of study
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Rate of viral clearance estimated under a hierarchical log-linear model fit to the serial viral load measurements over 5 days after enrolment. The viremia kinetics will be measured using the qRT-PCR assay, which will be performed on samples taken twice a day from day 1 to day 3 of study and then once a day on days 4 and 5 of study (total 9 samples per patient). |
From randomization until day 5 of study
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Number of AEs (grade 3, 4 and 5)
기간: Until day 30 post-enrolment
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All patients will be followed up daily until discharge and then at around days 30 after randomization to collect information on clinical progress of dengue illness and any adverse events occurring during the study course. All AEs and SAEs will be recorded. |
Until day 30 post-enrolment
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Area under the viremia curve
기간: From randomisation until day 5 of study
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Area under the curve (AUC) of the serial viremia measurements during the first 5 days of study |
From randomisation until day 5 of study
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Viral log reduction
기간: up to 48 hours of study
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Reduction of viremia at the 24 and 48 hours compared to baseline |
up to 48 hours of study
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NS1 clearance time
기간: up to day 5
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Time to NS1 clearance as estimated under a non-linear model |
up to day 5
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Number of patients progress to severe dengue (WHO 2009 criteria)
기간: From enrolment until discharge, assessed up to 30 days
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All patients will be followed up daily until discharge to collect information about the clinical progress of dengue |
From enrolment until discharge, assessed up to 30 days
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Number of patients requiring for ICU admission
기간: From enrolment until discharge, assessed up to 30 days
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All patients will be followed up daily until discharge to collect information about the clinical progress of dengue |
From enrolment until discharge, assessed up to 30 days
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Fever clearance time
기간: From enrolment until discharge, assessed up to 30 days
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Time elapsed from enrolment to the afebrile time-point (defined as body temperature <37.5 °C for at least 48 hours) |
From enrolment until discharge, assessed up to 30 days
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Platelet nadir
기간: Until day 30 post-enrolment
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The lowest platelet count recorded during admission |
Until day 30 post-enrolment
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Maximum AST/ALT
기간: Until day 30 post-enrolment
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The highest values of AST/ALT measured |
Until day 30 post-enrolment
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Change in haematocrit
기간: Until day 30 post-enrolment
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Change in haematocrit during the hospitalisation |
Until day 30 post-enrolment
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공동 작업자 및 조사자
수사관
- 수석 연구원: Sophie Yacoub, MD., PhD., University of Oxford, UK
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
- 71DX
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
The database may be shared with researchers not directly involved in this study but only after the main paper has been published and in accordance with OUCRU guidelines on data sharing. The database will only be shared if future publications are not compromised. No identifiable information will be shared with any other person/organisation than that authorised in the protocol.
IPD 공유 기간
starting 6 months after publications of study findings
IPD 공유 지원 정보 유형
- 연구_프로토콜
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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