Reproducibility of Malaria Challenge in Healthy Volunteers

Official Title: “Reproducibility of Malaria Challenge in Healthy Volunteers”

This is a prospective, single arm, single intervention safety and immunogenicity study in 6 healthy, malaria-naive adults, conducted to demonstrate the successful implementation of the well-established malaria challenge model at the Seattle Biomedical Research Institute (Seattle BioMed).

This study is designed to demonstrate the ability to inoculate malaria naive human volunteers with the Plasmodium falciparum strain of malaria sporozoites by the bite of infected mosquitoes under controlled conditions. Subjects are monitored closely for development of malaria and treated with standard doses of anti-malarial medications which the Plasmodium falciparum strain of malaria is known to be sensitive.

Study participants will undergo malaria sporozoite challenge with wild-type NF54 strain of Plasmodium falciparum sporozoites administered via the bite of five infected Anopheles stephensi mosquitoes under controlled containment conditions.

Participants will be closely monitored for acute reactogenicity and signs and/or symptoms of malaria infection, and from day five post-challenge, will have daily blood films examined for the presence of malaria parasites. Participants who develop malaria infection will be treated with a standard oral regimen of chloroquine, or other FDA-approved anti-malarial drugs, under direct observation. Participants will be treated upon first evidence of microscopic parasitemia or at day 18 if they remain negative. Participants will be housed with study staff in a local hotel for close observation from day 9 post-challenge, until three consecutive blood smears are negative and all symptoms have resolved, then followed weekly for a total of 8 weeks.

Follow-up for safety will be conducted at 4- and 6- months post-challenge.

Intervention(s) in this Clinical Trial

• Biological: Malaria challenge (wild-type NF54 strain Plasmodium falciparum sporozoites)
  • Malaria sporozoite challenge with the wild-type NF54 strain of Plasmodium falciparum delivered by the bite of five infected Anopheles stephensi mosquitoes.

Primary Measures

• Development of malaria parasitemia and time to parasitemia demonstrated on peripheral blood smear
  • Time Frame: Day 5 through Day 28 post challenge
    Safety Issue?: Yes

Secondary Measures

• Occurrence of unsolicited AEs
  • Time Frame: Day 0 through Day 56 post challenge
    Safety Issue?: Yes
• Local and systemic solicited adverse events (AEs)
  • Time Frame: Day 5 through Day 28 post challenge
    Safety Issue?: Yes
• Occurrence of serious AEs
  • Time Frame: Day 0 through Day 56 post challenge
    Safety Issue?: Yes
• Cell-mediated immune response to experimental malaria infection
  • Time Frame: Day 0 through Day 56 post challenge
    Safety Issue?: No
• Humoral immune responses to experimental malaria infection
  • Time Frame: Day 0 through Day 56 post challenge
    Safety Issue?: No

Inclusion Criteria:

• Age 18 to 50 years
• Male or non-pregnant female
• Good general health
• Hemoglobin, WBC, platelets and creatinine within normal ranges
• ALT, AST, bilirubin, alkaline phosphatase <1.25 times upper limit of normal
• Normal urine
• Negative HIV-1 and 2 blood test
• Negative Hepatitis B surface antigen (HBsAg)
• Negative anti-Hepatitis C virus antibodies (anti-HCV)
• Low risk for coronary heart disease (CHD)
• Ability and willingness to provide informed consent
• Assessment of Understanding questionnaire completed
• Reliable access to the trial center and availability for duration of study
• If the participant is biologically female, she must:
• Have negative serum or urine beta human chorionic gonadotropin pregnancy test performed within 3 days prior to challenge
• Agree to consistently use effective contraception from 21 days prior to enrollment for the duration of the study
• OR not be of reproductive potential
• OR be sexually abstinent
• Also agree not to seek pregnancy through alternative methods

Exclusion Criteria:

• Planned travel to malaria endemic area during the study period
• Recent travel to a malaria endemic area within 3 months of enrollment
• Prior receipt of an investigational malaria vaccine
• History of malaria diagnosis based on positive peripheral blood smear
• Use of malaria chemoprophylaxis with chloroquine within 5 months of malaria challenge, with atovaquone/proguanil within 2 months of malaria challenge or with mefloquine within 30 days prior to malaria challenge
• Recent or anticipated use of systemic antibiotics with anti-malarial effects during the study period
• Anticipated use of medications known to interact with chloroquine and/or atovaquone/proguanil during the study period
• Use of investigational or non-registered drug or vaccine within 30 days preceding challenge or planned use during the study period
• Immunosuppressive medications received within 6 months prior to challenge or planned use within 21 days after challenge
• Any vaccination received or planned within 30 days prior to challenge
• Blood products or immunoglobulins received within 120 days of challenge
• Screening laboratory abnormalities
• Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have clinically significant implications for current health status
• History of anaphylaxis
• History of severe allergic reactions to mosquito bites
• History of, or known active cardiac disease
• Elevated risk of coronary heart disease
• Clinically significant ECG findings
• Chronic or active neurologic disease
• History of splenectomy or functional asplenia
• History of psoriasis or porphyria
• History of ocular disease diagnosed by an ophthalmologist as retinopathy or visual field defects
• Acute illness at the time of enrollment
• Serologic positivity for HIV, hepatitis C and/or hepatitis b
• Pregnant or lactating female or female who intends to become pregnant during the study period
• Psychiatric condition that precludes compliance with the protocol including but not limited to: psychosis within the past 3 years OR ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years
• Suspected or known current alcohol abuse as defined by the American Psychiatric
• Association in DSM IV
• Recreational intravenous drug use in the last 12 months
• Any other finding that, in the judgement of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent or increase the risk of having an adverse outcome from participating in the study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Seattle Biomedical Research Institute Other

Overall Clinical Trial Officials and Contacts

Angela Talley, M.D. Principal Investigator Seattle Biomedical Research Institute  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01058226

Study ID Number: MC-001

ClinicalTrials.gov Identifier: NCT01058226

Health Authority: United States: Food and Drug Administration