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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02564471
Recruitment Status : Completed
First Posted : September 30, 2015
Last Update Posted : April 4, 2019
Sponsor:
Collaborators:
Walter Reed Army Institute of Research (WRAIR)
Kansas State University
Information provided by (Responsible Party):
Timothy Endy, MD MPH, State University of New York - Upstate Medical University

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.

Condition or disease Intervention/treatment Phase
Rabies Drug: Chloroquine Drug: Atovaquone and Proguanil Drug: Doxycycline Biological: Rabies Vaccine Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Effect of Antimalarial Drugs on the Immune Response to Rabies Vaccine for Post-exposure Prophylaxis. A Randomized, Open Label, Trial in Healthy US Adults Age 18-60 Years
Study Start Date : April 2016
Actual Primary Completion Date : August 2018
Actual Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rabies

Arm Intervention/treatment
Experimental: Chloroquine
Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base)
Drug: Chloroquine
FDA approve dosing schedule
Other Name: Chloroquine Phosphate

Biological: Rabies Vaccine
FDA approve dosing schedule
Other Name: RabAvert

Experimental: 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.

Drug: Atovaquone and Proguanil
FDA approve dosing schedule
Other Name: Malarone

Biological: Rabies Vaccine
FDA approve dosing schedule
Other Name: RabAvert

Experimental: Doxyclycline

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
FDA approve dosing schedule
Other Name: Doxycycline Hyclate

Biological: Rabies Vaccine
FDA approve dosing schedule
Other Name: RabAvert

Active Comparator: Rabies
RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.
Biological: Rabies Vaccine
FDA approve dosing schedule
Other Name: RabAvert




Primary Outcome Measures :
  1. Geometric Mean Titer (GMT) at 14 days post completion of four dose post exposure prophylaxis (PEP) with PCECV in each of the malaria prophylaxis groups with control to determine if a fifth dose of PEP at that point would be of any added value [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. GMT over protective titer prior to third dose and fourth dose and 28 days post fourth dose of PCECV [ Time Frame: 2 months ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  5. Any major psychiatric disorder, such as severe depression, severe anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. History of mild depression or anxiety disorder that are well controlled are not exclusion criteria.
  6. Use of any immunosuppressive drug at the time of the study or 30 days previously. Topical steroids will not be considered an immunosuppressive drug and their use will not be considered an exclusion criteria.
  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.

Temporary Exclusion Criteria: Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on day 0.. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided. If the delay for the febrile illness exceeds the window between screening and vaccination, or if deemed necessary by the investigator, a prospective subject may be re-screened once the fever has resolved.

Recent or scheduled receipt of any vaccine 4 weeks prior to day 0.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02564471


Locations
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United States, New York
State University of New York, Upstate Medical University (SUNY-UMU)
Syracuse, New York, United States, 13210
Sponsors and Collaborators
State University of New York - Upstate Medical University
Walter Reed Army Institute of Research (WRAIR)
Kansas State University
Investigators
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Principal Investigator: Mark E Polhemus, MD State University of New York - Upstate Medical University

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Responsible Party: Timothy Endy, MD MPH, Chair, Department of Microbiology and Immunology, State University of New York - Upstate Medical University
ClinicalTrials.gov Identifier: NCT02564471     History of Changes
Other Study ID Numbers: 790117
First Posted: September 30, 2015    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019

Additional relevant MeSH terms:
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Rabies
Rhabdoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Vaccines
Doxycycline
Chloroquine
Chloroquine diphosphate
Antimalarials
Atovaquone
Proguanil
Atovaquone, proguanil drug combination
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Amebicides
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics