Adaptive Dengue Antiviral Platform Trial (ADAPT)

Adaptive Dengue Antiviral Platform Trial (ADAPT): a Phase 2 Randomized, Adaptive, Open Label Trial for Antiviral Screening in Patients With Early Symptomatic 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

• 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

• Secondary objective:

  • To assess the effect of the experimental drug(s) in dengue patients on physiological, clinical and virological parameters

Study Overview

• Status: Recruiting
• Conditions: Dengue; Antiviral Drugs
• Intervention / Treatment: Drug: Molnupiravir 400 mg; Drug: VIS513 (a monoclonal antibody); Drug: Remdesivir 100mg

Detailed Description

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...).

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sophie Yacoub, MD., PhD.; Phone Number: +84 77728736; Email: syacoub@oucru.org
• Study Contact Backup: Name: Clinical Trials Unit Oxford University Clinical Research Unit; Phone Number: +84 28 3924 1983; Email: CTU-Ethics@oucru.org

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Not yet recruiting
    • Universiti Malaya Medical Centre
    • Contact: Hang Cheng Ong, Doctor
• Vietnam
  • Ho Chi Minh City, Vietnam, 700000
    • Recruiting
    • Hospital for Tropical Diseases, Ho Chi Minh city
    • Contact: Lan TH Nguyen, Doctor
    • Principal Investigator: Lan TH Nguyen, Doctor
    • Sub-Investigator: Trieu T Huynh, Doctor
    • Sub-Investigator: Tho V Phan, Doctor
    • Sub-Investigator: Huy X Vo, Doctor
    • Sub-Investigator: Huong TC Nguyen, Doctor
    • Sub-Investigator: Phong T Nguyen, Doctor
    • Sub-Investigator: Vien TD Tran, Doctor
    • Sub-Investigator: Men TH Pham, Doctor
    • Sub-Investigator: Quy T Vo, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care (arm A); Patients, who are randomly allocated into arm A will receive the standard of care (no study drug)
Experimental: Molnupiravir (arm B); Patients, who are randomly allocated into arm B, will receive 800mg po bid of Molnupiravir for 5 days	Drug: Molnupiravir 400 mg; 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.; Other Names: Molnupiravir STELLA 400mg
Experimental: 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.	Drug: VIS513 (a monoclonal antibody); 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.; Other Names: Dengue monoclonal antibody (Dengue mAb/ Dv Mab)
Experimental: Remdesivir (arm D); Patients, who are randomly allocated into arm D, will receive: Adults or children ≥ 40Kg: 200mg loading dose on day 1, followed by 100mg once daily from day 2 to day 5.; Children < 40Kg: 5mg/Kg loading dose on day 1, followed by 2.5mg/Kg once daily from day 2 to day 5.	Drug: Remdesivir 100mg; Remdesivir (GS-443902) is a nucleoside analogue - RNA dependent RNA polymerase inhibitor. In a meta-analysis of 10 RCTs and 32 observational studies reporting on the use of Remdesivir in COVID-19, remdesivir reduced mortality from severe disease and shortened time to clinical improvement. In this trial, its antiviral effectiveness on the early phase of dengue virus infection will be assessed; Other Names: VEKLURY™ for IV Infusion 100 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral clearance rate	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
Number of AEs (grade 3, 4 and 5)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the viremia curve	Area under the curve (AUC) of the serial viremia measurements during the first 5 days of study	From randomisation until day 5 of study
Viral log reduction	Reduction of viremia at the 24 and 48 hours compared to baseline	up to 48 hours of study
NS1 clearance time	Time to NS1 clearance as estimated under a non-linear model	up to day 5
Number of patients progress to severe dengue (WHO 2009 criteria)	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
Number of patients requiring for ICU admission	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
Fever clearance time	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
Platelet nadir	The lowest platelet count recorded during admission	Until day 30 post-enrolment
Maximum AST/ALT	The highest values of AST/ALT measured	Until day 30 post-enrolment
Change in haematocrit	Change in haematocrit during the hospitalisation	Until day 30 post-enrolment

Collaborators and Investigators

• Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; University Malaya Medical Centre, Malaysia
• Investigators: Principal Investigator: Sophie Yacoub, MD., PhD., University of Oxford, UK

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: August 6, 2024
• First Submitted That Met QC Criteria: August 11, 2024
• First Posted (Actual): August 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue; Therapeutics; Drug Administration Routes; Drug Therapy; Administration, Intravenous; Infusions, Parenteral; Infusions, Intravenous; remdesivir; molnupiravir
• Other Study ID Numbers: 71DX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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 Sharing Time Frame: starting 6 months after publications of study findings
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No