Adaptive Dengue Antiviral Platform Trial (ADAPT)

Oxford University Clinical Research Unit, Vietnam

Status and phase: Begins enrollment in 3 months; Phase 2

Conditions: Dengue; Antiviral Drugs

Treatments: Drug: Molnupiravir 400 mg; Drug: VIS513 (a monoclonal antibody)

Study type: Interventional

Funder types: Other

Identifiers

NCT06551844

71DX

Details and patient eligibility

About

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

Full 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...).

Enrollment: 500 estimated patients

Sex: All

Ages: 10+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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500 participants in 3 patient groups

Standard of care (arm A)

No Intervention group

Description:

Patients, who are randomly allocated into arm A will receive the standard of care (no study drug)

Molnupiravir (arm B)

Experimental group

Description:

Patients, who are randomly allocated into arm B, will receive 800mg po bid of Molnupiravir for 5 days

Treatment:

Drug: Molnupiravir 400 mg

Monoclonal antibody (arm C)

Experimental group

Description:

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.

Treatment:

Drug: VIS513 (a monoclonal antibody)