Anakinra in Dengue With Hyperinflammation ( AnaDen )

NCT05611710 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: 60DX223004/Z/21/Z
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effect of anakinra in dengue patients with hyperinflammation as compared to placebo Primary Objective: To evaluate the efficacy of Anakinra in moderate-severe dengue patients with hyperinflammation. Secondary Objectives:

• To assess the safety of anakinra therapy in dengue with hyperinflammation
• To assess the effect of anakinra therapy in patients with dengue on physiological, clinical and virological parameters
• To assess the immunomodulation effects of anakinra in dengue
• Immune cell signatures in dengue with and without anakinra
• To assess difference in gene expression between treatment group compared to non-treatment population

Conditions

Dengue; Dengue With Warning Signs; Anakinra; Severe Dengue; Immuno-modulation; Anti-inflammatory Agents; Macrophage Activation Syndrome; Hyperinflammatory Syndrome; Cytokine Storm

Keywords

Dengue; Hyperinflammatory syndrome; Anakinra; Vietnam

Outcome Measures

Primary Outcomes (1)

• Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days

  Change in mSOFA score over 4 days after randomization (min score= 0, max score = 24, higher scores mean worse outcomes)

  baseline, up to day 4

Secondary Outcomes (17)

• Mortality

  Up to day 30

• Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7

  baseline, day 7

• Number of days treated in Intensive care unit (ICU)

  Up to day 30

• Number of days treated in hospital

  Up to day 30

• Number of participants with Serious Adverse Events (SAEs)

  Day 1-5 and Day 6-30

Other Outcomes (1)

• Change in immune cells

  Up to day 90

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo.

Drug: Placebo

Anakinra

EXPERIMENTAL

The intervention group will include 80 dengue patients with warning signs or severe dengue receiving anakinra.

Drug: Anakinra

Interventions

Placebo DRUG

Drug: Placebo, with visually matched clear syringes * Adults (≥16 years) and children (12-16 years, \> 50Kg) will receive 2 syringes of placebo via IV route, twice daily for 4 days * Children (12-16 years, \< 50Kg) will receive no more than 1 syringe of placebo via IV route, twice daily for 4 days

Placebo

Anakinra DRUG

Drug: Anakinra * Adults (≥16 years) and children (12-16 years, \> 50Kg) will receive 200mg of anakinra (2 syringes) via IV route, twice daily for 4 days * Children (12-16 years, \< 50Kg) will receive 2mg/Kg of anakinra via IV route, twice daily for 4 days (no more than 1 syringe of anakinra, twice daily for 4 days)

Anakinra

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients hospitalised with a clinical diagnosis of dengue and at least 1 warning sign(s) (see appendix) or severe dengue to Emergency department/inpatient wards/Intensive Care wards (ICU),
• Ferritin levels \> 2000ng/mL
• ≥ 12 years of age
• Written informed consent or assent to participate in the study
• Agree to come back for 2 follow up visits around day 30 of illness (maximum 5 weeks) and at 3 months

You may not qualify if:

• Pregnancy
• Localizing features suggesting an alternative/additional diagnosis, e.g. pneumonia, sepsis
• Patients taking immunosuppressive drugs or other biologics in last 1 month
• Patients with underlying malignancy or immunosuppression
• Children \<12 years
• Have end-stage renal failure (baseline GFR \< 30ml/min)
• Being treated for TB
• Taking any drug with significant interaction with anakinra
• The study physician judges that the patient is unlikely to attend follow up visit at around 3-4 weeks after fever onset - e.g. due to long travelling distance from the clinic

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam: collaborator
• Wellcome Trust: collaborator

Study Sites (1)

Hospital for Tropical Diseases

Ho Chi Minh City, Vietnam

Location

Related Publications (40)

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MeSH Terms

Conditions

Dengue; Severe Dengue; Macrophage Activation Syndrome; Cytokine Release Syndrome

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Sophie Yacoub

  University of Oxford, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double blinded, placebo controlled trial of anakinra in patients with dengue with warning signs or severe dengue

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: November 10, 2022
• Study Start: January 2, 2023
• Primary Completion: October 20, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

VN (1)