Blood-Stage Plasmodium Vivax Cell Bank
Condition: Malaria
MeSH terms: Malaria
Intervention: HMPBS02-Pv
Intervention description: The blood-stage P. vivax master cell bank HMPBS02-Pv was also produced using blood collected from a consenting patient with naturally acquired malaria infection. The malaria infection was confirmed to be P. vivax by species-specific PCR at Pathology Queensland (accredited by the Australian National Association of Testing Authorities) and further confirmed by deep sequencing at the Sanger Institute. The clinical response to antimalarial chemotherapy was also demonstrated with this donor, who was successfully cured with artemether/lumefantrine.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Malaria; Parasitemia; IBSM; inoculation; Challenge

Summary:

      Background:

      Malaria is caused by a parasite (a type of germ called P. vivax) that is carried by
      mosquitoes. The disease is transmitted to people when they are bitten by infected mosquitoes.
      To make drugs and vaccines for malaria, researchers need malaria-infected blood. Plasmodium
      vivax cell cultures are currently not cultured in vivo, and thus establishing a blood bank
      from P. vivax infections will be vital for future research.

      Objective:

      The goal of this study is to infect people with early-stage malaria, then collect infected
      blood samples to store in a cell bank for future use.

      Eligibility:

      Healthy adults ages 18-50 who will not be living alone during the study period.

      Design:

      Participants will be screened with a physical exam, heart health test, and medical history.
      They will have blood and urine tests. They will take a mental health survey. They must pass
      an exam to prove they understand the study.

      Participants will have red blood cells infected with P. vivax injected into an arm vein. They
      will be observed for side effects. They will get a thermometer to measure their temperature
      at home.

      For the next 3 days, they will be monitored via phone call or text. Starting on day 4 after
      the infection, they will have daily study visits to give blood samples. They will likely
      develop symptoms of malaria, such as fever, chills, headache, and muscle pain.

      Participants will be admitted to the hospital for 2-3 days when either they develop symptoms
      or the daily blood tests detect a certain amount of parasites. Once malaria is confirmed, a
      sample of their blood will be collected for the cell bank. Then they will be treated for
      malaria with oral medication that will cure the infection. Those who do not develop malaria
      will begin treatment after 15 days.

      Participants will have follow-up visits 28 and 90 days after infection.

      Participation will last for 3-5 months.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        All of the following criteria must be fulfilled for a participant to participate in this
        trial:

          -  Age >=18 and <=50 years.

          -  In good general health and without clinically significant medical history.

          -  Does not live alone from study Day 0 until the end of the antimalarial drug treatment.

          -  Malaria comprehension exam completed, passed (a score of >=80% or per investigator s
             discretion) and reviewed prior to enrollment.

          -  Reliable access to the NIH CC and availability to participate for duration of study.

          -  Females of childbearing potential must be willing to use reliable contraception (as
             defined below) from 21 days prior to study Day 0 to 28 days following IBSM.

          -  Sign written informed consent prior to undertaking any study-related procedure.

        EXCLUSION CRITERIA:

        A participant will be excluded from participating in this trial if any one of the following
        criteria is fulfilled:

          -  Currently breastfeeding (if female).

          -  Pregnant as determined by a positive urine or serum human choriogonadotropin
             (Beta-hCG) test (if female).

          -  Planned travel to a malaria-endemic area during the study period and up to 2 weeks
             following the EOS visit.

          -  History of recent travel to or residence in a P. vivax malaria-endemic region for more
             than 2 weeks during the past 5 years.

          -  Planned travel to a malaria-endemic region during the course of the study (for endemic
             regions, see www.cdc.gov/malaria/travelers/country_table).

          -  Any history of confirmed malaria diagnosis on peripheral blood smear or by clinical
             history

          -  Participation in a previous malaria challenge study.

          -  Screening laboratory parameters outside of local lab normal range, to include
             serum-corrected calcium, creatinine, hepatic transaminase enzymes (ALT, AST), total
             bilirubin (unless the participant has documented Gilbert syndrome), and hemoglobin.
             Participants may be included at the investigator s discretion for not clinically
             significant values outside of normal range.

          -  Abnormal urinalysis as defined by positive urine glucose, protein, and hemoglobin.
             Participant can be included if investigator determine the abnormality is not
             clinically significant.

          -  Duffy blood group negative (male or female).

          -  ABO blood type other than O (male or female).

          -  Rh blood group negative (females of childbearing potential).

          -  Anticipated use during the study period, or use within the following periods prior to
             enrollment of any of the following: Investigational malaria vaccine within the last 2
             years; Malaria chemoprophylaxis within the past 6 months; Chronic systemic
             immunosuppressive medications (>14 days) within 6 months; Blood products or
             immunoglobulins within the previous 6 months; Systemic antibiotics or medications with
             potential antimalarial effects within the past 6 weeks; Investigational or
             non-registered product or vaccine within 30 days; Receipt of any vaccination within 28
             days prior to P. vivax IBSM; Medications known to interact with
             artemether/lumefantrine; Anticoagulants within the past 28 days.

          -  History of:

               -  Sickle cell disease, sickle cell trait, or other hemoglobinopathies.

               -  Splenectomy or functional asplenia.

               -  Systemic anaphylaxis.

               -  Any allergic reactions to artemether/lumefantrine, chloroquine (or any
                  4-aminoquinolines), artemether or other artemisinin derivatives, or their
                  excipients.

               -  History of malignancy of any organ system (other than localized basal cell
                  carcinoma of the skin or in situ cervical cancer), treated or untreated, within 5
                  years of screening, regardless of whether there is evidence of local recurrence
                  or metastases.

               -  Blood transfusion.

          -  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 and participation
             in the study in the opinion of the investigator.

          -  Vital signs taken after 5 minutes of resting in seated or supine position that fall
             outside the following ranges:

               -  Systolic blood pressure <=90 mm Hg or >=140 mm Hg.

               -  Diastolic blood pressure <=50 mm Hg or >=90 mm Hg.

               -  Heart rate <=40 bpm or >=100 bpm.

          -  Body mass index less than 17.0 or greater than 35.0 kg/m2 at the time of screening.

          -  History of, or known active cardiac disease including: (1) prior myocardial infarction
             (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart
             disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic
             attack; (8) exertional chest pain or shortness of breath; (9) symptomatic cardiac
             arrhythmias; (10) clinically relevant bradycardia; or (11) other heart conditions
             under the care of a doctor.

          -  Clinically significant electrocardiogram (ECG) findings as determined by the expert
             study cardiologist, or QTcF >=450 ms, or presence of second- or third-degree
             atrioventricular block or abnormal T wave morphology.

          -  Moderate or high risk for coronary heart disease based on National Health and
             Nutrition Examination Survey (NHANES) I cardiovascular risk assessment (Appendix A).

          -  Family history of sudden death or of congenital prolongation of the QTc interval or
             known congenital prolongation of the QTc interval or any clinical condition known to
             prolong the QTc interval.

          -  History of electrolyte disturbances, particularly hypokalemia, hypocalcemia, or
             hypomagnesemia.

          -  Acute infectious disease or fever (e.g., temperature >=38.5 degrees C) within the 5
             days prior to inoculation with malaria parasites.

          -  Evidence of acute illness within the 4 weeks prior to screening that the investigator
             deems may compromise participant safety.

          -  Positive result on any of the following tests: hepatitis B surface antigen (HBsAg),
             anti-hepatitis C virus (anti-HCV) antibodies, and anti-human immunodeficiency virus 1
             and 2 antibodies (anti-HIV1 and anti HIV2 Ab).

          -  Positive urine drug test for any drug unless there is an explanation acceptable to the
             investigator.

          -  Elevated serum ethanol level.

          -  Psychiatric condition that precludes compliance with the protocol.

          -  Suspected or known current alcohol or drug abuse as defined by the American
             Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders,
             5th Edition, at the discretion of the investigator.

          -  Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for
             the duration of admission. Participants may smoke up to 5 cigarettes or equivalent per
             day for the rest of the study.

          -  History or presence of alcohol abuse (alcohol consumption of more than 4 standard
             drinks per day), drug habituation, or any prior intravenous usage of an illicit
             substance.

          -  Excessive consumption of beverages or food containing xanthine bases (such as Red
             Bull, chocolate, etc.), or more than 400 mg of caffeine per day (equivalent to more
             than 4 cups of coffee per day).

          -  Ingestion of any poppy seeds within the 24 hours prior to the screening blood test
             (participants will be advised by phone not to consume any poppy seeds in this time
             period).

          -  Use of prescription drugs or non-prescription drugs and herbal supplements (such as St
             John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the
             inoculation administration. (Note: diazepam interferes with the analysis of blood
             levels of chloroquine and thus should not have been used for at least 8 weeks prior to
             administration of the study drug). If needed (i.e., an incidental and limited need),
             ibuprofen up to 1.2 g/day or acetaminophen up to 4 g/day is acceptable. The
             participant must inform the investigator of any ibuprofen or acetaminophen use at the
             next convenient time. Limited use of other non-prescription medications or dietary
             supplements not believed to affect participant safety or the overall results of the
             study may be permitted on a case-by-case basis following approval by the sponsor in
             consultation with the investigator. Participants are requested to refrain from taking
             non-approved concomitant medications from recruitment until the conclusion of the
             study.

          -  Clinical trial staff with direct involvement in the conduct of the trial are excluded
             from participation.

          -  Participating in other clinical trials involving investigational interventions or
             off-label medication use during the study period or within the 12 weeks preceding
             study day 0. Participation in other trials such as observational or imaging studies
             will be discussed with the investigators.

          -  Blood donation of any volume within 4 weeks prior to study day 0, or participation in
             any research study involving blood sampling (more than 450 mL/unit of blood), or blood
             donation to Red Cross (or other) blood bank within 8 weeks prior to study day 0.

          -  Unwillingness to defer blood donations for at least 3 years.

          -  Unwillingness to abstain from consumption of quinine-containing foods/beverages, such
             as tonic water or lemon bitter, from inoculation (study day 0) to the end of
             antimalarial treatment.

          -  Unwillingness to abstain from consumption of grapefruit or Seville oranges from
             inoculation (study day 0) to the end of antimalarial treatment.

          -  Any participant without a good peripheral venous access.

          -  Participant who, in the judgment of the investigator, is likely to be noncompliant
             during the study, or is unable to cooperate because of a language or mental deficit.

          -  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 participant s ability to give informed consent