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

NCT ID: NCT02564471

Last Updated: 2021-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-11
• Study Completion Date: 2019-02-28

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.

Detailed Description

Rabies is present on all continents where U.S. military personnel deploy, including countries where malaria is also endemic and where U.S. military personnel are required to take malaria prophylaxis. Rabies post-exposure prophylaxis in unvaccinated individuals who are not on malaria prophylaxis consists of four, 1.0-mL intramuscular (IM) injections of the purified chick embryo cell (PCECV) rabies vaccine on days 0, 3, 7, and 14. The current Advisory Committee on Immunization Practices (ACIP) guidelines recommend that exposed persons who are taking malaria prophylaxis should receive a fifth dose of rabies vaccine 28 days after the exposure. These guidelines do not differentiate between drugs used for malaria prophylaxis This study will administer the post-exposure regimen to volunteers from a US population of military age who are taking one of three malaria prophylaxis regimens or no malaria prophylaxis. The goal of this study is to asses if individuals on malaria prophylaxis achieve the required rabies titer after completion of the four dose regimen.

Obtaining rabies vaccine and rabies immune globulin in a deployed setting can be challenging. A full understanding of the requirements for protecting exposed individuals is necessary for appropriate decision making in a resource-constrained environment.

Conditions

Rabies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Chloroquine

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

Group Type: EXPERIMENTAL

Chloroquine

Intervention Type: DRUG

FDA approve dosing schedule

Rabies Vaccine

Intervention Type: BIOLOGICAL

FDA approve dosing schedule

Atovaquone and Proguanil (Malarone)

Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride.

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

Group Type: EXPERIMENTAL

Atovaquone and Proguanil

Intervention Type: DRUG

FDA approve dosing schedule

Rabies Vaccine

Intervention Type: BIOLOGICAL

FDA approve dosing schedule

Doxycycline

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.

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

FDA approve dosing schedule

Rabies Vaccine

Intervention Type: BIOLOGICAL

FDA approve dosing schedule

Rabies

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

Group Type: ACTIVE_COMPARATOR

Rabies Vaccine

Intervention Type: BIOLOGICAL

FDA approve dosing schedule

Interventions

Chloroquine

FDA approve dosing schedule

Intervention Type: DRUG

Atovaquone and Proguanil

FDA approve dosing schedule

Intervention Type: DRUG

Doxycycline

FDA approve dosing schedule

Intervention Type: DRUG

Rabies Vaccine

FDA approve dosing schedule

Intervention Type: BIOLOGICAL

Other Intervention Names

Chloroquine Phosphate; Malarone; Doxycycline Hyclate; RabAvert

Eligibility Criteria

Inclusion Criteria

1. Provide signed and dated informed consent form.

2. Willing to comply with all study procedures and be available for the duration of the study.

3. Male or female, aged ≥ 18 to ≤ 60 years on day of inclusion.

4. In good general health based on medical history and physical exam

Exclusion Criteria

1. 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.

2. 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.

3. Previous history of receiving the rabies vaccine.

4. Previous history of receiving rabies immune globulin.

7. Any immunosuppressive disorder, such as HIV infection, common variable immunodeficiency, active cancers or chemotherapy.

8. History of renal insufficiency or requiring dialysis.

9. 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.

10. 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.

11. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Walter Reed Army Institute of Research (WRAIR)

FED

Sponsor Role: collaborator

Kansas State University

OTHER

Sponsor Role: collaborator

State University of New York - Upstate Medical University

OTHER

Sponsor Role: lead

Responsible Party

Timothy Endy, MD MPH

Chair, Department of Microbiology and Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Timothy Endy, MD

Role: PRINCIPAL_INVESTIGATOR

State University of New York - Upstate Medical University

Locations

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

Syracuse, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 31743394 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

790117

Identifier Type: -

Identifier Source: org_study_id