Clinical trial NCT06551844: Adaptive Dengue Antiviral Platform Trial
Official title: Adaptive Dengue Antiviral Platform Trial (ADAPT): a Phase 2 Randomized, Adaptive, Open Label Trial for Antiviral Screening in Patients With Early Symptomatic Dengue
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Dengue
Antiviral Drugs
Lead sponsor: Oxford University Clinical Research Unit, Vietnam
Sponsor class: OTHER
Collaborators: name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
First posted: 2024-08-13
Enrollment: 500
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a phase 2 randomized, adaptive, open label trial for antiviral screening in patients with dengue presenting at the healthcare settings within 48 hours.
Primary purpose: TREATMENT

Brief summary: 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

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. Other sites and countries may be added in due course.

This is a continually running adaptive platform trial, which begins with two initial candidate drugs (a total of 3 arms): molnupiravir 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...).

Eligibility criteria: 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.

Primary outcomes:
measure: Viral clearance rate
timeFrame: From randomization until day 5 of study
measure: Number of AEs (grade 3, 4 and 5)
timeFrame: Until day 30 post-enrolment
Secondary outcomes:
measure: Area under the viremia curve
timeFrame: From randomisation until day 5 of study
measure: Viral log reduction
timeFrame: up to 48 hours of study
measure: NS1 clearance time
timeFrame: up to day 5
measure: Number of patients progress to severe dengue (WHO 2009 criteria)
timeFrame: From enrolment until discharge, assessed up to 30 days
measure: Number of patients requiring for ICU admission
timeFrame: From enrolment until discharge, assessed up to 30 days
measure: Fever clearance time
timeFrame: From enrolment until discharge, assessed up to 30 days
measure: Platelet nadir
timeFrame: Until day 30 post-enrolment
measure: Maximum AST/ALT
timeFrame: Until day 30 post-enrolment
measure: Change in haematocrit
timeFrame: Until day 30 post-enrolment
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Hospital for Tropical Diseases at Ho Chi Minh city
Study officials:
affiliation: University of Oxford, UK
name: Sophie Yacoub, MD., PhD.
role: PRINCIPAL_INVESTIGATOR
References: