Trial record 5 of 7 for:    Open Studies | (insect OR mosquito OR bee) AND (bites OR stings)

Immunization Via Mosquito Bite With Radiation-attenuated Sporozoites (IMRAS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by U.S. Army Medical Research and Materiel Command
Sponsor:
Collaborators:
Seattle Biomedical Research Institute
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01994525
First received: November 19, 2013
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

This study is to assess the safety, tolerability, and biomarkers of protection in healthy malaria-naïve adults, who will receive bites from Anopheles stephensi mosquitoes either infected with Plasmodium falciparum Sporozoites (PfRAS) (true-immunization) or noninfected (mock-immunization).


Condition Intervention Phase
Malaria
Biological: PfRAS
Biological: Placebo
Other: Challenge
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase 1 Trial With Challenge to Assess the Safety and Biomarkers of Protection in Malaria-naïve Adults of Immunization Via Mosquito Bite With Radiation-Attenuated Plasmodium Falciparum Sporozoites (IMRAS)

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Solicited adverse events [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Occurrence of solicited adverse events (AE) from administration of study immunization (PfRAS)

  • Unsolicited adverse events [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Occurrence of unsolicited adverse events (AEs) from administration of immunization (PfRAS)

  • Laboratory adverse events [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Occurrence of laboratory AEs from administration of study immunization (PfRAS)

  • Serious adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Occurrence of serious adverse events (SAEs) from administration of immunization (PfRAS)

  • Signs and symptoms related to malaria infection [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Occurrence of signs and symptoms related to malaria infection starting 7 days post-Controlled Human Malaria Infection (CHMI) (these will not be recorded as adverse events because they are expected as a result of malaria infection)

  • Parasitemia [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Development of parasitemia and time to parasitemia after malaria challenge


Secondary Outcome Measures:
  • Identify and validate immunological PBMC biomarkers [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Compare Peripheral Blood Mononuclear Cell(s) (PBMC) read-outs between protected and nonprotected subjects and between immunized and mock-immunized subjects.

  • Identify and validate immunological serum biomarkers [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Compare serum read-outs between protected and nonprotected subjects and between immunized and mock-immunized subjects.

  • Identify and validate whole blood immunological biomarkers [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Compare whole blood read-outs between protected and nonprotected subjects and between immunized and mock-immunized subjects.


Estimated Enrollment: 52
Study Start Date: December 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: PfRAS-infected

5 doses (immunizations) of approximately 200 infectious bites (200-400 bites total) from PfRAS-infected mosquitoes (true-immunization). The target dose is 960 infectious bites.

Challenge occurs 3 weeks after final immunization.

Biological: PfRAS
Radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) administered by the bite of infected Anopheles stephensi mosquitoes
Other Names:
  • True-immunization
  • PfRAS infected Anopheles stephensi mosquitoes
Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.
Placebo Comparator: Cohort 1: Noninfected

Placebo immunization. 5 doses of approximately 200 infectious bites (200-400 bites total) from irradiated uninfected mosquitoes (mock-immunization). The target dose is 960 infectious bites.

Challenge occurs 3 weeks after final immunization.

Biological: Placebo
Administered by the bite of noninfected Anopheles stephensi mosquitoes
Other Names:
  • Mock-immunization
  • Noninfected Anopheles stephensi mosquites
Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.
Cohort 1: Nonimmunized

No protective intervention given.

Challenge occurs directly after screening.

Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.
Experimental: Cohort 2: PfRAS-infected

3 to 7 doses (immunizations) of approximately 200 infectious bites (200-400 bites total) from PfRAS-infected mosquitoes (true-immunization). The target dose is dependent on protection results in cohort 1.

Challenge occurs 3 weeks after final immunization.

Biological: PfRAS
Radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) administered by the bite of infected Anopheles stephensi mosquitoes
Other Names:
  • True-immunization
  • PfRAS infected Anopheles stephensi mosquitoes
Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.
Placebo Comparator: Cohort 2: Noninfected

Placebo. 3 to 7 doses of approximately 200 infectious bites (200-400 bites total) from irradiated, uninfected mosquitoes (true-immunization). The target dose is dependent on protection results in cohort 1.

Challenge occurs 3 weeks after final immunization.

Biological: Placebo
Administered by the bite of noninfected Anopheles stephensi mosquitoes
Other Names:
  • Mock-immunization
  • Noninfected Anopheles stephensi mosquites
Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.
Cohort 2: Nonimmunized

No protective intervention given.

Challenge occurs directly after screening.

Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.
Experimental: Hyperimmunity PfRAS-infected

Cohort 1 sub-cohort

3 doses (immunizations) of approximately 200 infectious bites (200-400 bites total) from PfRAS-infected mosquitoes. The target dose is dependent on protection results in cohort 1. This arm will receive the first 3 immunizations of Cohort 2.

Challenge occurs 3 weeks after final immunization.

Biological: PfRAS
Radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) administered by the bite of infected Anopheles stephensi mosquitoes
Other Names:
  • True-immunization
  • PfRAS infected Anopheles stephensi mosquitoes
Other: Challenge
5 infectious Anopheles stephensi mosquito bites carrying infectious Plasmodium falciparum sporozoites within a controlled clinical environment.

Detailed Description:

This is a Phase 1 open-labeled study. In addition to safety and tolerability of Plasmodium falciparum Sporozoites (PfRAS), this study is a comprehensive, systems biology-based effort to identify and validate biomarkers of protection with PfRAS immunization, comparing sterility protected to nonprotected study subjects. The goal of the trial design is to achieve approximately 50% sterile protection in order to facilitate the identification of biomarkers and correlates of protection.

Following true-immunization or mock-immunization, study subjects and nonimmunized infectivity controls will receive a challenge via the bites of 5 An stephensi mosquitoes carrying infectious P falciparum sporozoites within a controlled clinical environment (controlled human malaria infection, CHMI) to determine the level of sterile protection.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults (male or non-pregnant, non-breastfeeding female) 18-50 years of age (inclusive).
  • Available and willing to participate for duration of study.
  • Able and willing to provide written informed consent.
  • Able to complete an Assessment of Understanding with a score of at least 70% correct.
  • In good general health with no clinically significant health problems as established by medical history, physical exam and laboratory screening.
  • Females of childbearing potential must have a negative pregnancy test at screening and agree to not become pregnant or breastfeed for the duration of the study. She must be willing to use a reliable form of contraception during the study. Reliable forms of birth control include use of condoms, diaphragm or cervical cap, birth control pills, IUD or sperm killing products.
  • Agree to refrain from blood donation (except as required in this study) for 3 years following P falciparum challenge.
  • Agree not to travel to a malaria-endemic region during the study.
  • Good peripheral venous access.

Exclusion Criteria:

  • Positive Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) serology.
  • Positive sickle cell screening test, including evidence of sickle trait.
  • Positive by CSP or AMA1 ELISpot assay or ELISA
  • Anemia (below normal reference laboratory value of hemoglobin) on screening.
  • Weight less than 110 pounds.
  • Any history of malaria infection or travel to a malaria endemic region within 6 months prior to first immunization.
  • History of long-term residence (> 5 years) in area known to have significant transmission of P falciparum [cumulative lifetime exposure].
  • Use of systemic immunosuppressant pharmacotherapy (inhaled and topical steroids are allowed) within 60 days of scheduled leukapheresis or immunization.
  • Current significant medical condition (cardiovascular, hepatic, renal, pulmonary, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination (includes bleeding disorders).
  • Plan for surgery between enrollment and day 28 post-challenge.
  • Receipt of immunoglobulin and/or any blood products within 90 days of scheduled leukapheresis or immunization.
  • Evidence of increased cardiovascular disease risk (defined as > 5%-10%, 5-year risk) as determined by the method of Gaziano (2008). Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking status, body mass index (BMI, kg/m2), reported diabetes status, and blood pressure.
  • An abnormal electrocardiogram (ECG), defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block.
  • History of a splenectomy.
  • History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives. This may include psychiatric disorders (such as personality disorders, anxiety disorders, or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult.
  • History of anaphylactic or other severe response to mosquito bites (history of local hypersensitivity reactions is allowed).
  • History of retinal disease, visual field changes, psoriasis, porphyria, or known allergy to the anti-malarial chloroquine phosphate, which will be used to treat subjects developing malaria after CHMI.
  • Participation in any study involving any investigational vaccine or drug within 90 days prior to the screening visit, or plan to participate in another investigational vaccine/drug research during or within 1 month following participation in this study.
  • Use or planned use of any drug with antimalarial activity that would coincide with immunization or challenge.
  • Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin.
  • Any other significant findings which, in the investigator's judgment, may substantially increase.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01994525

Contacts
Contact: Bradley Hickey, MD 850-479-0751 Bradley.Hickey@med.navy.mil
Contact: Judith Epstein, MD 301-252-9026 Judith.Epstein@med.navy.mil

Locations
United States, Maryland
Naval Medical Research Center Clinical Trials Center (CTC) Recruiting
Bethesda, Maryland, United States, 20889
Contact: Bradley Hickey, MD    850-479-0751    Bradley.Hickey@med.navy.mil   
Contact: Judith Epstein, MD    301-295-8025    Judith.Epstein@med.navy.mil   
Principal Investigator: Bradley Hickey, MD         
Sub-Investigator: Judith Epstein, MD         
Sub-Investigator: Alexandra Singer, MD         
Sub-Investigator: Cindy Tamminga, MD         
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Seattle Biomedical Research Institute
Bill and Melinda Gates Foundation
Investigators
Principal Investigator: Bradley Hickey, MD Naval Medical Research Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01994525     History of Changes
Other Study ID Numbers: S-12-22
Study First Received: November 19, 2013
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on August 21, 2014