Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)

NCT07016321 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB00486563
• Study Type: interventional
• Target: 600
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this study is to evaluate the efficacy and safety of emetine administered orally for symptomatic patients aged 18-65 years infected with the dengue virus. The main questions it aims to answer are:

1. 1.Does emetine reduce 28-day mortality or progression to severe dengue (severe plasma leakage, severe bleeding, or severe organ involvement)?
2. 2.What are the safety outcomes of emetine, including serious adverse events and toxicities?
3. 3.Take either 6mg emetine, 12mg emetine, or a placebo pill for 7 consecutive days as part of the treatment regimen.
4. 4.Have blood samples taken for at least 5 days to monitor viral load, inflammatory markers, and safety parameters.
5. 5.Be monitored by healthcare staff for daily vital signs and symptoms for clinical assessments for 28 days.

Conditions

Dengue

Outcome Measures

Primary Outcomes (3)

• Evaluate effectiveness of emetine in dengue patients assessed by 28-day mortality or progression

  28-day mortality or progression to severe dengue, defined as severe plasma leakage, severe bleeding, or severe organ involvement (death and severe dengue will be assessed as a composite outcome)

  28 days

• Safety of emetine assessed by number of adverse events

  Record serious adverse events and toxicities by organ-system

  Up to 28 days

• Safety of emetine assessed by rate of drug discontinuation

  Evaluate the safety of emetine assessed by rate of drug discontinuation

  Up to 28 days

Secondary Outcomes (12)

• Recovery (≥ 3 days without symptoms)

  Up to 14 days

• Time to Virologic Clearance of Dengue Virus by Qualitative RT-PCR

  Pre-dose (day 0), day 3, and day 5

• Quantitative Viral Load Assessment by RT-PCR Cycle Threshold (Ct) Values

  Days 0,3, 5

• Changes in inflammatory marker measured by hematocrit

  Days 0 to 5

• Changes in inflammatory marker measured by white blood count

  Day 0-5

Study Arms (3)

Emetine 6 mg

ACTIVE COMPARATOR

Participants take 6mg Emetine pill for 10 consecutive days

Drug: Emetine Hydrochloride 6mg

Emetine 12 mg

ACTIVE COMPARATOR

Participants take 12mg Emetine pill for 10 consecutive days

Drug: Emetine Hydrochloride 12mg

Placebo

PLACEBO COMPARATOR

Participant take a placebo for 10 consecutive days

Drug: Placebo

Interventions

Emetine Hydrochloride 6mg DRUG

To administer Emetine Hydrochloride 6mg orally for 10 consecutive days to evaluate the efficacy and safety of emetine for symptomatic dengue patients.

Emetine 6 mg

Placebo DRUG

Participant take a placebo for 10 consecutive days.

Placebo

Emetine Hydrochloride 12mg DRUG

To administer Emetine Hydrochloride 12mg orally for 10 consecutive days to evaluate the efficacy and safety of emetine for symptomatic dengue patients.

Emetine 12 mg

Eligibility Criteria

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

You may qualify if:

• Age 18 to 65 years
• Admitted to the hospital
• Laboratory-confirmed infection with dengue virus within the last 5 days and preferably within the last 3 days. Testing for dengue virus using positive Nonstructural protein 1(NS1) strip assay or reverse-transcriptase polymerase chain reaction (RT-PCR)
• Having two or more clinical symptoms (fever, headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, or leucopenia, gastrointestinal symptoms) with the onset of fever within 72 hours of presentation, and
• Able to provide voluntary informed consent and comply with all study procedures and visits.

You may not qualify if:

• Age ≥65 years
• Pregnant or breastfeeding
• Current or recent use of the study drug
• Known allergy to study drug
• Current or planned participation in another pharmacological interventional trial in the next 10 days
• Participants with known past history of dengue infection
• Participants on aspirin, anticoagulants, or with other conditions that might increase the risk of bleeding
• Participants on immunosuppressive agents, including long-term steroids
• Severe dengue as defined by the WHO 2009 revised case classification.
• Individuals with long-term immunosuppressive agents such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or those on systemic corticosteroid therapy
• History of prior vaccination against dengue fever within one year.
• Patients who have recently used ayurvedic or herbal medications for dengue or any other conditions in the last 7 days (eg, Papaya leaf extract)

Sponsors & Collaborators

• Johns Hopkins University: lead
• Bharatpur Hospital Chitwan: collaborator

Study Sites (2)

Johns Hopkins University, Division of Infectious Disease

Baltimore, Maryland, 21231, United States

Location

Bharatpur Hospital

Bharatpur-10, Chitwan, Nepal

Location

Related Publications (8)

• Choy KT, Wong AY, Kaewpreedee P, Sia SF, Chen D, Hui KPY, Chu DKW, Chan MCW, Cheung PP, Huang X, Peiris M, Yen HL. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020 Jun;178:104786. doi: 10.1016/j.antiviral.2020.104786. Epub 2020 Apr 3.

  PMID: 32251767 BACKGROUND

• Ooi EE. Repurposing Ivermectin as an Anti-dengue Drug. Clin Infect Dis. 2021 May 18;72(10):e594-e595. doi: 10.1093/cid/ciaa1341. No abstract available.

  PMID: 33124646 BACKGROUND

• Bhat CS, Shetty R, Sundaram B, Ramanan AV. Immunomodulatory therapy in dengue: need for clinical trials and evidence base. Arch Dis Child. 2023 Jun;108(6):451-452. doi: 10.1136/archdischild-2022-324100. Epub 2022 Jun 9. No abstract available.

  PMID: 35680407 BACKGROUND

• Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016 Aug 18;2:16055. doi: 10.1038/nrdp.2016.55.

  PMID: 27534439 BACKGROUND

• Beesetti H, Khanna N, Swaminathan S. Investigational drugs in early development for treating dengue infection. Expert Opin Investig Drugs. 2016 Sep;25(9):1059-69. doi: 10.1080/13543784.2016.1201063. Epub 2016 Jun 24.

  PMID: 27322111 BACKGROUND

• Entner N, Grollman AP. Inhibition of protein synthesis: a mechanism of amebicide action of emetine and other structurally related compounds. J Protozool. 1973 Feb;20(1):160-3. doi: 10.1111/j.1550-7408.1973.tb06025.x. No abstract available.

  PMID: 4347870 BACKGROUND

• Bleasel MD, Peterson GM. Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2. Pharmaceuticals (Basel). 2020 Nov 27;13(12):428. doi: 10.3390/ph13120428.

  PMID: 33261173 BACKGROUND

• Grollman AP. Structural basis for inhibition of protein synthesis by emetine and cycloheximide based on an analogy between ipecac alkaloids and glutarimide antibiotics. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1867-74. doi: 10.1073/pnas.56.6.1867. No abstract available.

  PMID: 16591432 BACKGROUND

MeSH Terms

Conditions

Dengue

Interventions

Emetine

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Kunchok Dorjee, MBBS, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kunchok Dorjee, MBBS, PhD

CONTACT

4105027135; kdorjee1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to one of three arms: intervention arm #1 (6 mg emetine), intervention arm #2 (12 mg emetine), or the control arm (matching oral placebo) based on a pre-designed scheme of block randomization.

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: June 11, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): May 3, 2029
• Last Updated: December 12, 2025

Record last verified: 2025-12

Locations

US (1); NE (1)