Zkušební verze adaptivní platformy proti horečce dengue (ADAPT)
Adaptivní studie platformy proti horečce dengue (ADAPT): Randomizovaná, adaptivní, otevřená studie fáze 2 pro antivirový screening u pacientů s časnou symptomatickou horečkou dengue
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
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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 studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Sophie Yacoub, MD., PhD.
- Telefonní číslo: +84 77728736
- E-mail: syacoub@oucru.org
Studijní záloha kontaktů
- Jméno: Clinical Trials Unit Oxford University Clinical Research Unit
- Telefonní číslo: +84 28 3924 1983
- E-mail: CTU-Ethics@oucru.org
Studijní místa
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Kuala Lumpur, Malajsie, 59100
- Zatím nenabíráme
- Universiti Malaya Medical Centre
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Kontakt:
- Hang Cheng Ong, Doctor
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Ho Chi Minh City, Vietnam, 700000
- Nábor
- Hospital for Tropical Diseases, Ho Chi Minh city
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Kontakt:
- Lan TH Nguyen, Doctor
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Vrchní vyšetřovatel:
- Lan TH Nguyen, Doctor
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Dílčí vyšetřovatel:
- Trieu T Huynh, Doctor
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Dílčí vyšetřovatel:
- Tho V Phan, Doctor
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Dílčí vyšetřovatel:
- Huy X Vo, Doctor
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Dílčí vyšetřovatel:
- Huong TC Nguyen, Doctor
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Dílčí vyšetřovatel:
- Phong T Nguyen, Doctor
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Dílčí vyšetřovatel:
- Vien TD Tran, Doctor
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Dílčí vyšetřovatel:
- Men TH Pham, Doctor
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Dílčí vyšetřovatel:
- Quy T Vo, Doctor
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Žádný zásah: 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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Experimentální: 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.
Ostatní jména:
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Experimentální: 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.
Ostatní jména:
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Experimentální: 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.
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Viral clearance rate
Časové okno: 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)
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Area under the viremia curve
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: Until day 30 post-enrolment
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Change in haematocrit during the hospitalisation |
Until day 30 post-enrolment
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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Sophie Yacoub, MD., PhD., University of Oxford, UK
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Nemoci přenášené vektorem
- Nemoci přenášené komáry
- Infekce
- RNA virové infekce
- Virová onemocnění
- Arbovirové infekce
- Flavivirové infekce
- Infekce Flaviviridae
- Hemoragické horečky, virové
- Dengue
- Terapeutika
- Trasy pro správu léčiva
- Léčba
- Administrace, intravenózní
- Infuze, parenterální
- Infuze, intravenózní
- Remdesivir
- Molnlnupiravir
Další identifikační čísla studie
- 71DX
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu 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.
Časový rámec sdílení IPD
starting 6 months after publications of study findings
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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