Essai de plateforme antivirale adaptative contre la dengue (ADAPT)
Essai sur la plateforme antivirale adaptative contre la dengue (ADAPT) : un essai de phase 2 randomisé, adaptatif et ouvert pour le dépistage antiviral chez les patients atteints de dengue symptomatique précoce
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
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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...).
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: Sophie Yacoub, MD., PhD.
- Numéro de téléphone: +84 77728736
- E-mail: syacoub@oucru.org
Sauvegarde des contacts de l'étude
- Nom: Clinical Trials Unit Oxford University Clinical Research Unit
- Numéro de téléphone: +84 28 3924 1983
- E-mail: CTU-Ethics@oucru.org
Lieux d'étude
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Kuala Lumpur, Malaisie, 59100
- Pas encore de recrutement
- Universiti Malaya Medical Centre
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Contact:
- Hang Cheng Ong, Doctor
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Ho Chi Minh City, Viêt Nam, 700000
- Recrutement
- Hospital for Tropical Diseases, Ho Chi Minh city
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Contact:
- Lan TH Nguyen, Doctor
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Chercheur principal:
- Lan TH Nguyen, Doctor
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Sous-enquêteur:
- Trieu T Huynh, Doctor
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Sous-enquêteur:
- Tho V Phan, Doctor
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Sous-enquêteur:
- Huy X Vo, Doctor
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Sous-enquêteur:
- Huong TC Nguyen, Doctor
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Sous-enquêteur:
- Phong T Nguyen, Doctor
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Sous-enquêteur:
- Vien TD Tran, Doctor
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Sous-enquêteur:
- Men TH Pham, Doctor
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Sous-enquêteur:
- Quy T Vo, Doctor
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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 d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Aucune intervention: 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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Expérimental: 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.
Autres noms:
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Expérimental: 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.
Autres noms:
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Expérimental: 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.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Viral clearance rate
Délai: 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)
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Area under the viremia curve
Délai: 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
Délai: 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
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Until day 30 post-enrolment
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Change in haematocrit during the hospitalisation |
Until day 30 post-enrolment
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Collaborateurs et enquêteurs
Les enquêteurs
- Chercheur principal: Sophie Yacoub, MD., PhD., University of Oxford, UK
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies à transmission vectorielle
- Maladies transmises par les moustiques
- Infections
- Infections par virus à ARN
- Maladies virales
- Infections à arbovirus
- Infections à flavivirus
- Infections à Flaviviridae
- Fièvres hémorragiques, virales
- Dengue
- Thérapeutique
- Voies d'administration du médicament
- Pharmacothérapie
- Administration, intraveineuse
- Infusions, parentéraux
- Infusions, intraveineuses
- remdesivir
- molnupiravir
Autres numéros d'identification d'étude
- 71DX
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime 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.
Délai de partage IPD
starting 6 months after publications of study findings
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
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