Próba adaptacyjnej platformy przeciwwirusowej przeciwko dendze (ADAPT)
Badanie adaptacyjnej platformy przeciwwirusowej przeciw wirusowi dengi (ADAPT): randomizowane, adaptacyjne, otwarte badanie fazy 2 dotyczące antywirusowych badań przesiewowych u pacjentów z wczesnymi objawami dengi
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
Przegląd badań
Status
Warunki
Interwencja / Leczenie
Szczegółowy opis
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...).
Typ studiów
Zapisy (Szacowany)
Faza
- Faza 2
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Sophie Yacoub, MD., PhD.
- Numer telefonu: +84 77728736
- E-mail: syacoub@oucru.org
Kopia zapasowa kontaktu do badania
- Nazwa: Clinical Trials Unit Oxford University Clinical Research Unit
- Numer telefonu: +84 28 3924 1983
- E-mail: CTU-Ethics@oucru.org
Lokalizacje studiów
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Kuala Lumpur, Malezja, 59100
- Jeszcze nie rekrutacja
- Universiti Malaya Medical Centre
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Kontakt:
- Hang Cheng Ong, Doctor
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Ho Chi Minh City, Wietnam, 700000
- Rekrutacyjny
- Hospital for Tropical Diseases, Ho Chi Minh city
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Kontakt:
- Lan TH Nguyen, Doctor
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Główny śledczy:
- Lan TH Nguyen, Doctor
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Pod-śledczy:
- Trieu T Huynh, Doctor
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Pod-śledczy:
- Tho V Phan, Doctor
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Pod-śledczy:
- Huy X Vo, Doctor
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Pod-śledczy:
- Huong TC Nguyen, Doctor
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Pod-śledczy:
- Phong T Nguyen, Doctor
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Pod-śledczy:
- Vien TD Tran, Doctor
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Pod-śledczy:
- Men TH Pham, Doctor
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Pod-śledczy:
- Quy T Vo, Doctor
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Zadanie sekwencyjne
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Brak interwencji: 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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Eksperymentalny: 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.
Inne nazwy:
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Eksperymentalny: 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.
Inne nazwy:
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Eksperymentalny: 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.
Inne nazwy:
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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Viral clearance rate
Ramy czasowe: 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)
Ramy czasowe: 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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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Area under the viremia curve
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: Until day 30 post-enrolment
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Change in haematocrit during the hospitalisation |
Until day 30 post-enrolment
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Współpracownicy i badacze
Śledczy
- Główny śledczy: Sophie Yacoub, MD., PhD., University of Oxford, UK
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Choroby przenoszone przez wektory
- Choroby przenoszone przez komary
- Infekcje
- Zakażenia wirusem RNA
- Choroby wirusowe
- Infekcje arbowirusowe
- Infekcje Flawiwirusowe
- Infekcje Flaviviridae
- Gorączki krwotoczne, wirusowe
- Denga
- Lecznictwo
- Drogi podawania leków
- Terapia lecznicza
- Podawanie, dożylne
- Infuzje, pozajelitowe
- Infuzje, dożylne
- Remdesivir
- Molnupiravir
Inne numery identyfikacyjne badania
- 71DX
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu IPD
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.
Ramy czasowe udostępniania IPD
starting 6 months after publications of study findings
Typ informacji pomocniczych dotyczących udostępniania IPD
- PROTOKÓŁ BADANIA
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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