Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis.

NCT02564471 | Completed Phase 4 Results

• 1 other identifier: 790117
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

This is an exploratory trial to evaluate the effect of antimalarial drugs on the immune response generated by rabies vaccine when administered for post-exposure prophylaxis. This study will use the FDA approved post-exposure prophylaxis vaccine regimen (without rabies immune globulin) in the presence or absence of an FDA-approved malaria chemoprophylaxis regimen.

Conditions

Rabies

Outcome Measures

Primary Outcomes (1)

• Geometric Mean Titer (GMT) 14 Days Post Fourth Dose Post Exposure Prophylaxis (PEP) With Purified Chick Embryo Cell Vaccine (PCECV) in Each Malaria Prophylaxis Group Compared to Control to Determine if a Fifth Dose of PEP Would Add Value

  Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21, and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3,7 and 14 (dose 4). Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of \>0.5 IU/ml against rabies virus as protective. Descriptive analyses were based on samples taken 14 days after dose 4, (e.g., at 6 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Arms and at 4 weeks for Rabies Arm).

  6 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and at 4 weeks for Rabies Group

Secondary Outcomes (3)

• GMT Over Protective Titer Prior to Third Dose of PCECV

  21 days for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and 7 days for Rabies Arm

• GMT Over Protective Titer Prior Fourth Dose of PCECV

  28 days for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and 14 days for Rabies Arm

• GMT Over Protective Titer 28 Days Post Fourth Dose of PCECV

  Up to 8 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and up to 6 weeks for Rabies Arm

Study Arms (4)

Chloroquine

EXPERIMENTAL

Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base)

Drug: Chloroquine; Biological: Rabies Vaccine

Atovaquone and Proguanil (Malarone)

EXPERIMENTAL

Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.

Drug: Atovaquone and Proguanil; Biological: Rabies Vaccine

Doxycycline

EXPERIMENTAL

Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.

Drug: Doxycycline; Biological: Rabies Vaccine

Rabies

ACTIVE COMPARATOR

RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.

Biological: Rabies Vaccine

Interventions

Chloroquine DRUG

FDA approve dosing schedule

Also known as: Chloroquine Phosphate

Chloroquine

Atovaquone and Proguanil DRUG

FDA approve dosing schedule

Also known as: Malarone

Atovaquone and Proguanil (Malarone)

Doxycycline DRUG

FDA approve dosing schedule

Also known as: Doxycycline Hyclate

Doxycycline

Rabies Vaccine BIOLOGICAL

FDA approve dosing schedule

Also known as: RabAvert

Atovaquone and Proguanil (Malarone); Chloroquine; Doxycycline; Rabies

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide signed and dated informed consent form.
• Willing to comply with all study procedures and be available for the duration of the study.
• In good general health based on medical history and physical exam

You may not qualify if:

• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination.
• Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Previous history of receiving the rabies vaccine.
• Previous history of receiving rabies immune globulin.
• Any immunosuppressive disorder, such as HIV infection, common variable immunodeficiency, active cancers or chemotherapy.
• History of renal insufficiency or requiring dialysis.
• Have any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
• Identified as an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employee or the Investigator.
• Previous adverse reaction to any of the antimalarial drugs used in this study.
• Recent or scheduled receipt of any vaccine 4 weeks prior to day 0.

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Kansas State University: collaborator

Study Sites (1)

State University of New York, Upstate Medical University (SUNY-UMU)

Syracuse, New York, 13210, United States

Location

Related Publications (1)

• Endy TP, Keiser PB, Cibula D, Abbott M, Ware L, Thomas SJ, Polhemus ME. Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen. J Infect Dis. 2020 Mar 2;221(6):927-933. doi: 10.1093/infdis/jiz558.

  PMID: 31743394 RESULT

MeSH Terms

Conditions

Rabies

Interventions

Chloroquine; chloroquine diphosphate; atovaquone, proguanil drug combination; Doxycycline; Rabies Vaccines

Condition Hierarchy (Ancestors)

Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Timothy Endy
• Organization: SUNY Upstate Medical University

endyt@upstate.edu

3154647692

Study Officials

• Timothy Endy, MD

  State University of New York - Upstate Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Department of Microbiology and Immunology

Study Record Dates

• First Submitted: September 29, 2015
• First Posted: September 30, 2015
• Study Start: November 11, 2016
• Primary Completion: August 1, 2018
• Study Completion: February 1, 2019
• Last Updated: May 13, 2021
• Results First Posted: April 13, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)