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Malaria Challenge in Healthy Volunteers (ITV)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Seattle Biomedical Research Institute
ClinicalTrials.gov Identifier:
NCT01500980
First received: December 19, 2011
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to determine if sterile, protective immunity to malaria can be induced by malaria parasite exposure limited to the early liver stage of the parasite lifecycle.


Condition Intervention Phase
Malaria
Biological: P. falciparum infection
Drug: Chloroquine
Drug: Primaquine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Infection-Treatment-Vaccination for Plasmodium Falciparum

Resource links provided by NLM:


Further study details as provided by Seattle Biomedical Research Institute:

Primary Outcome Measures:
  • Microscopic evaluation of peripheral blood smears [ Time Frame: Up to 182 days ] [ Designated as safety issue: Yes ]
    Detection for evidence of patent parasitemia and time to parasitemia following challenge with homologous P. falciparum sporozoites in subjects with confirmed exposure to P. falciparum sporozoites and early liver stage parasites only

  • qRT-PCR [ Time Frame: Up to 182 days ] [ Designated as safety issue: Yes ]
    qRT-PCR evaluation for detection of subpatent parasitemia following a single episode of ITV

  • Number of subjects with adverse events [ Time Frame: up to 182 days ] [ Designated as safety issue: Yes ]
    Occurrence of solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) during the study period


Secondary Outcome Measures:
  • ELISA [ Time Frame: up to 182 days ] [ Designated as safety issue: No ]
    Humoral immune responses pre-/post- ITV and subsequent challenge by binding ELISA for antibodies to P. falciparum liver stage, blood stage, and pre-erythrocytic antigens.

  • IFN-y ELISPOT [ Time Frame: up to 182 days ] [ Designated as safety issue: No ]
    Evaluation of cell-mediated immune responses to P. falciparum liver-stage and pre-erythrocytic antigens pre-/post- ITV and subsequent challenge by (IFN-y) ELISPOT assay on peripheral blood mononuclear cells

  • ICS assay [ Time Frame: up to 182 days ] [ Designated as safety issue: No ]
    Detection of cell-mediated immune responses pre-/post- ITV and subsequent challenge by ICS assay for P. falciparum pre-erythrocytic antigens on peripheral blood mononuclear cells


Enrollment: 36
Study Start Date: December 2011
Study Completion Date: November 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pilot Phase
Pilot phase will include 6 subjects and will investigate the timing of PQ dosing relative to parasite exposure.
Biological: P. falciparum infection
P. falciparum (NF54 strain) infection delivered by the bites of 12 - 15 infected A. stephensi mosquitos
Drug: Chloroquine
Weekly chloroquine dosing (600 mg loading dose, 300 mg thereafter)
Drug: Primaquine
Primaquine (45 mg) on day 2 or 3 post ITV infection
Experimental: Chloroquine, ITV, primaquine, malaria challenge Biological: P. falciparum infection
P. falciparum (NF54 strain) infection delivered by the bites of 12 - 15 infected A. stephensi mosquitos
Drug: Chloroquine
Weekly chloroquine dosing (600 mg loading dose, 300 mg thereafter)
Drug: Primaquine
Primaquine (45 mg) on day 2 or 3 (pending results of pilot study) post ITV infection
Active Comparator: Sporozoite negative vaccine Drug: Chloroquine
Weekly chloroquine dosing (600 mg loading dose, 300 mg thereafter)
Drug: Primaquine
Primaquine (45 mg) on day 2 or 3 (pending results of pilot study) post ITV infection
Active Comparator: Primaquine placebo Biological: P. falciparum infection
P. falciparum (NF54 strain) infection delivered by the bites of 12 - 15 infected A. stephensi mosquitos
Drug: Chloroquine
Weekly chloroquine dosing (600 mg loading dose, 300 mg thereafter)
No Intervention: malaria challenge

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Male and non-pregnant females age 18 to 50 years
  • Good general health status as demonstrated by medical history, physical exam, and screening laboratory test performed within 90 days of enrollment
  • Ability and willingness to provide informed consent
  • No laboratory evidence of hematologic, hepatic, or renal disease
  • Assessment of Understanding questionnaire completed and passed prior to enrollment
  • Reliable access to the clinical trials centers and availability to participate for duration of study
  • If the subject is biologically female and of reproductive potential she must agree to consistent pregnancy prevention

Exclusion Criteria:

  • Recent travel to a malaria endemic area within 6 months of enrollment
  • Planned travel to a malaria endemic area during the study period
  • History of confirmed malaria diagnosis on peripheral blood smear
  • Anticipated use during the study period, or use within the following periods prior to enrollment:

    1. Investigational malaria vaccine at any time
    2. Malaria chemoprophylaxis within 6 months
    3. Chronic systemic immunosuppressive medications within 6 months
    4. Blood products or immunoglobulins within 120 days
    5. Investigational product or vaccine within 30 days
    6. Systemic antibiotics with antimalarial effects within 30 days
    7. Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to each ITV infection and challenge
    8. Medications known to interact with primaquine, chloroquine or atovaquone/proguanil (only during the study period)
  • History of:

    1. Sickle cell disease, sickle cell trait, or other hemoglobinopathies
    2. Splenectomy or functional asplenia
    3. Systemic anaphylaxis
    4. Gelatin allergy
    5. Severe allergic reactions to mosquito bites of study drugs
    6. Documented history of chronic or active neurologic disease
    7. Psoriasis or porphyria
    8. Ocular diseases including retinopathy or visual field defects
  • Glucose 6 phosphate dehydrogenase (G6PD) deficiency
  • 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 in the opinion of the Investigator.
  • Weight <55 kg or >90 kg; body mass index (BMI) <18.5% or >31%
  • History of known active cardiac disease or stroke
  • Clinically significant abnormal screening electrocardiogram (ECG)
  • Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment
  • Acute illness at the time of enrollment
  • Pregnant or nursing female
  • Infection with HIV, Hepatitis B, Hepatitis C
  • Psychiatric condition that precludes compliance with the protocol
  • Suspected or known current alcohol or drug abuse
  • Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a subject's ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study
  • Clinical trial staff with direct involvement in the conduct of the trial
  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: NCT01500980

Locations
United States, Washington
Seattle Biomedical Research Institute's Malaria Clinical Trials Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Seattle Biomedical Research Institute
Investigators
Principal Investigator: Sara Healy, M.D. MPH Seattle Biomedical Research Institution
  More Information

No publications provided

Responsible Party: Seattle Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT01500980     History of Changes
Other Study ID Numbers: MC-003
Study First Received: December 19, 2011
Last Updated: December 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Seattle Biomedical Research Institute:
malaria
challenge
P. falciparum
prevention

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Chloroquine
Chloroquine diphosphate
Primaquine
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimalarials
Antinematodal Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Filaricides
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014