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A Systems Biology Approach to Malaria Immunity

This study is currently recruiting participants.
Verified July 19, 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT03014258
First Posted: January 9, 2017
Last Update Posted: September 15, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose

This is a phase I study that will assess the acquisition of immunity to Pf malaria over the course of 4 sequential Controlled Human Malaria Infections (CHMI) over 3 years, in 10 healthy adult participants. The study is expected to last for 48 months and will include 28 healthy male and female volunteers (10 study volunteers and 18 naïve controls to confirm Pf infectivity during the 2nd -4th CHMI challenges) ages18 to 45 years, inclusive, from the greater Baltimore community.

The primary objective of this study is to determine whether protective immunity against parasite infection develops following repeat CHMI.


Condition Intervention Phase
Plasmodium Falciparum Infection Biological: NF54 P. falciparum malaria challenge Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Systems Biology Approach to Malaria Immunity Repetitive Controlled Human Malaria Infection (CHMI) Study in Malaria-Naïve Adults Using NF54 Strain Plasmodium Falciparum (Pf)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of a positive malaria smear [ Time Frame: Study Days 6-29 post-CHMI ]
  • Occurrence of parasites using real-time quantitative PCR [ Time Frame: Study Days 6-29 post-CHMI ]
  • Quantification of parasites using real-time quantitative PCR [ Time Frame: Study Days 6-29 post-CHMI ]

Secondary Outcome Measures:
  • Occurrence of fever (>38oC) attributable to malaria [ Time Frame: Study Days 6-29 post-CHMI ]
  • Occurrence of signs and symptoms attributable to malaria (malaise, chills/rigors, nausea, vomiting, dizziness, arthralgia, abdominal pain, myalgia, and headache) [ Time Frame: Study Days 6-29 ]
  • Percentage of naïve and activated effector and memory B and T-cell, NK cell, monocyte and dendritic cell populations [ Time Frame: Study Days 6, 8, 13 and 7 days after a parasite-positive smear or Study Day 21 if aparasitemic ]
  • Percentage of Pf sporozoites and blood stage parasites that react with antibodies [ Time Frame: Study Day 6, 8, 13 and 7 days after a parasite-positive smear or Study Day 21 if aparasitemic ]

Estimated Enrollment: 28
Actual Study Start Date: June 7, 2017
Estimated Study Completion Date: November 1, 2020
Estimated Primary Completion Date: November 1, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Malaria-naïve Infectivity Control 1
1 CHMI challenge at month 8, n=6 immunologic malaria-naive
Biological: NF54 P. falciparum malaria challenge
Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.
Active Comparator: Malaria-naïve Infectivity Control 2
1 CHMI challenge at month 20, n=6 immunologic malaria-naive
Biological: NF54 P. falciparum malaria challenge
Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.
Active Comparator: Malaria-naïve Infectivity Control 3
1 CHMI challenge at month 32, n=6 immunologic malaria-naive
Biological: NF54 P. falciparum malaria challenge
Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.
Experimental: Repeat CHMI
1 Mock Challenge followed by 4 CHMI challenges, N=10
Biological: NF54 P. falciparum malaria challenge
Aseptically-raised A. stephensi female mosquitoes infected with aseptically-raised P. falciparum parasites of the NF54 strain.

Detailed Description:
This is a phase I study that will assess the acquisition of immunity to Pf malaria over the course of 4 sequential Controlled Human Malaria Infections (CHMI) over 3 years, in 10 healthy adult participants. 10 subjects will initially be challenged with 5 uninfected mosquitoes (mock), followed by 4 challenges with 5 mosquitoes infected with drug sensitive, P. falciparum parasites (strain NF54) 2, 8, 20, and 32 months later. For the final three infective CMHIs six additional immunologic malaria-naïve subjects will be enrolled and challenged as infectivity controls. All volunteers (repeat CHMI subjects and infectivity controls) will be evaluated as part of an inpatient stay to diagnose Pf malaria infection and treat with Coartem® (artemether/lumefantrine) or Malarone® (Atovaquone/proguanil). Inpatient observation will occur from Study Days 9-19 or until three-day directly observed therapy for P. falciparum infection is complete and two negative smears separated by a time interval >12 hours have been documented. A third negative smear >12 hours after the previous two inpatient smears will be documented to affirm malaria cure. The repeat CHMI subjects will have additional outpatient visits days 1, 3, 5, and 7 after the challenge to obtain blood samples to monitor the development of immunity. The study is expected to last for 48 months and will include 28 healthy male and female volunteers (10 study volunteers and 18 naïve controls to confirm Pf infectivity during the 2nd -4th CHMI challenges) ages18 to 45 years, inclusive, from the greater Baltimore community. The primary objective of this study is to determine whether protective immunity against parasite infection develops following repeat CHMI. The secondary objectives are to: 1) determine whether clinical signs and symptoms of malaria decrease in intensity and duration following repeat CHMI, 2) identify which PBMCs are activated and proliferate after each exposure to compare responses over time and to sequential CHMI, 3) track the production of antibodies that react with P. falciparum sporozoites and blood stage parasites.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or non-pregnant/non-lactating female between the ages of 18 and 45 years, inclusive.
  2. Able and willing to participate for the duration of the study.
  3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  4. Able and willing to complete the informed consent process.
  5. Willing to donate blood for sample storage to be used for future research (Note: refusal to allow future use is exclusionary).
  6. Willing to refrain from blood donation to blood banks for 3 years following P. falciparum CHMI.
  7. Agrees not to travel to a malaria endemic region during the entire course of study participation.
  8. Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) = / <35.

    Laboratory Criteria within 56 days prior to enrollment:

  9. Hemoglobin = />11.2 g/dL for women; = />12.6 g/dL for men.
  10. Platelet count within institutional normal range
  11. Alanine aminotransferase (ALT) = /< upper limit of normal
  12. Serum creatinine = /< upper limit of normal.
  13. Negative for HIV and Hepatitis B/C infection.

    Laboratory Criterion documented any time prior to enrollment:

  14. Negative sickle cell screening test.

    Female-Specific Criteria:

  15. Negative ß-HCG pregnancy test (serum) on day of screening or urine pregnancy test at subsequent time points for women of childbearing potential.
  16. Women of childbearing potential (exclusive of women in a same sex relationship) must agree to use effective means of birth control.* * (e.g. oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner). Women with a history of amenorrhea (> 1 year duration) or surgical or chemical sterilization (e.g. tubal ligation, hysterectomy, other) must provide written documentation of infertility from a health care provider).

Exclusion Criteria:

  1. Women who are breast-feeding or planning to become pregnant during the time interval needed to complete the study.
  2. Receipt of a malaria vaccine in a prior clinical trial.
  3. Any history of malaria infection.
  4. Evidence of increased cardiovascular disease risk; defined as >10% five year risk by the non-laboratory method.
  5. Current use of systemic immunosuppressant pharmacotherapy.
  6. History of a splenectomy, sickle cell disease or sickle cell trait.
  7. Known history of anaphylactic response to mosquito-bites; or known allergy to artemether lumefantrine or atovaquone or proguanil or other component of the product.
  8. Participation in any study involving investigational vaccine or drug within 4 weeks prior to enrollment, or expects to receive vaccine or drug during the 2-month post-challenge period.
  9. Use or planned use of any drug with anti-malarial activity that would coincide with challenge.
  10. Anticipated use of medications known to cause drug reactions with atovaquone-proguanil (Malarone®) such as cimetidine, metoclopramide, antacids, and kaolin.
  11. Plans to undergo surgery (elective or otherwise) between enrollment and 4 weeks (28 days) after any of the challenges.
  12. Received a licensed vaccine within 1 month prior to enrollment in this study or expects to receive one during the 2 month post challenge period.
  13. History of psychiatric disorders or behavioral tendencies (including active alcohol or drug abuse) that in the opinion of the investigator would make compliance with the protocol difficult* *Medical and psychiatric illness defined as personality disorders, anxiety disorders, or schizophrenia or social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent or to comply with the protocol schedule
  Contacts and Locations
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): NCT03014258


Contacts
Contact: Kim C Williamson 17735083631 kim.williamson@usuhs.edu

Locations
United States, Maryland
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore Recruiting
Baltimore, Maryland, United States, 21201-1509
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03014258     History of Changes
Other Study ID Numbers: 15-0058
5U01AI110852-04 ( U.S. NIH Grant/Contract )
First Submitted: December 15, 2016
First Posted: January 9, 2017
Last Update Posted: September 15, 2017
Last Verified: July 19, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Biology
falciparum
Immunity
Infections
Malaria
Pf
Plasmodium
Systems

Additional relevant MeSH terms:
Infection
Malaria
Protozoan Infections
Parasitic Diseases