Study of Controlled Human Malaria Infections to Evaluate Protection After Intravenous or Intramuscular Administration of PfSPZ Vaccine in Malaria-Naive Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:
NCT02015091
First received: December 18, 2013
Last updated: July 23, 2014
Last verified: December 2013
  Purpose

Background:

- People bitten by mosquitoes carrying weakened malaria parasites could fight off the disease if later exposed to normal malaria parasites. Scientists have discovered how to make the weakened parasites, which can be injected by the PfSPZ vaccine. Researchers want to see if people who receive the vaccine get malaria after being bitten in a controlled setting (a controlled human malaria infection, CHMI).

Objective:

- To see if the PfSPZ malaria vaccine is safe and prevents malaria in a controlled setting.

Eligibility:

- Healthy adults 18 45 years old.

Design:

  • Participants will be screened with medical history, physical exam, blood and lab tests, and EKG.
  • Participants will be split into 8 groups, to be in the study for 3 12 months.
  • Participants will receive 3 5 vaccinations, injected by a needle in an arm vein or muscle.
  • Participants will keep a health diary and be contacted by phone.
  • For CHMI, a cup with mosquitoes carrying malaria is applied to participants arm for 5 minutes. Five mosquitoes at a time are used, until 5 have bitten. Some groups will be exposed to malaria more than once.
  • After CHMI, participants will visit the clinic very frequently (including daily visits for 12 days) for 28 days.
  • Blood will be drawn at most visits, from 1 to 20 tubes. Physical exam and medical history may also be repeated
  • Participants who develop malaria will be treated immediately at the clinic. Standard treatment takes 72 hours. Malaria symptoms may last up to 3 days.

Condition Intervention Phase
Malaria
Prevention and Control
Acquired Immunity
Parasitemia
Biological: PfSPZ
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: VRC 314: A Phase 1, Open-Label, Clinical Trial With Experimental Controlled Human Malaria Infections (CHMI) to Evaluate Safety and Durability of Protection Following Intravenous and Intramuscular Administration of PFSPZ Vaccine in Malaria-Naive Adults

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary objectives of the study are related to the safety and tolerability of vaccinations by the IV and IM routes of administration and protection against the Plasmodium falciparum challenge. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objective is related to the durability of protection at 20-26 weeks after the last vaccination. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: December 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: PfSPZ
    N/A
Detailed Description:

VRC 314 is designed as an open-label evaluation of the safety, tolerability, immunogenicity and protective efficacy of the PfSPZ Vaccine. This vaccine administered at 1.35 x 10(5) SPZ per injection by the IV route on a schedule of 5 vaccinations was previously shown to confer protection in all vaccinated subjects against Controlled Human Malaria Infections (CHMI) performed shortly after last vaccination; however there was limited durability of protection in a small number of subjects. in this study, 1.35 x 10(5) SPZ per injection by the IV route will be given to substantiate the initial results with this dose for protection against CHMI. In addition, 2.7 x 10(5) SPZ IV per injection on schedules of 3 to 5 vaccinations will be evaluated for protection against CHMI conducted at 3 weeks and 24 weeks after completion of vaccinations. Also, one group will receive 2.2 x 10(6) SPZ IM, with half of the amount administered in each arm on a schedule with 4 vaccination time-points.

The primary objectives of the study are related to the safety and tolerability of vaccinations by the IV and IM routes of administration and protection against Plasmodium falciparum (Pf) challenge performed via a well-established CHMI procedure early (2-4 weeks) after completing schedules of 3 to 5 vaccinations. The secondary objective is related to the durability of protection at 20-26 weeks after the last vaccination and exploratory objectives are related to the immunogenicity of the PfSPZ Vaccine and identifying potential immune correlates of protection.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

A volunteer must meet all of the following criteria to be included:

  1. 18 to 45 years old adults.
  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.
  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) less than or equal to 35 for vaccine groups or BMI less than or equal to 40 for control groups.
  9. If enrolling into a Group with an IV vaccination schedule, then the physical exam must include assessment that there is adequate bilateral antecubital fossa venous access.

    Laboratory Criteria within 56 days prior to enrollment:

  10. Hemoglobin greater than or equal to 11.2 g/dL for women; greater than or equal to 12.6 g/dL for men.
  11. Differential and platelet count either within institutional normal range or accompanied by site physician approval.
  12. Alanine aminotransferase (ALT) less than or equal to 1.25 x upper limit of normal (ULN) for vaccine groups or less than or equal to 1.75 x ULN for CHMI control groups.
  13. Serum creatinine less than or equal to upper limit of normal.
  14. Negative for HIV infection.

    Laboratory Criterion documented any time prior to enrollment:

  15. Negative sickle cell screening test.

    Female-Specific Criteria:

  16. Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of childbearing potential.
  17. A woman of childbearing potential must agree to use an effective means of birth control throughout the duration of study participation.

EXCLUSION CRITERIA:

A volunteer will be excluded if one or more of the following conditions apply:

  1. Woman who is 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. Plan for major surgery between enrollment and challenge.
  8. Known allergy to any component of the vaccine formulation; history of anaphylactic response to mosquito-bites; or known allergy to chloroquine phosphate, atovaquone or proguanil.
  9. Participation in any study involving another investigational vaccine or drug within 12 weeks prior to enrollment, or plan to participate in another investigational vaccine/drug research during the study.
  10. Personal beliefs that prohibit the receiving of vaccine product containing human serum albumin within the diluent.
  11. Use or planned use of any drug with anti-malarial activity that would coincide with study vaccination or challenge.
  12. History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine.
  13. Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin.
  14. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, history of a suicide plan or attempt.
  15. Any medical, psychiatric, 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
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: NCT02015091

Contacts
Contact: Floreliz H Mendoza (301) 451-8715 vaccines@nih.gov

Locations
United States, Maryland
University of Maryland Center for Vaccine Dev, Baltimore Recruiting
Baltimore, Maryland, United States, 21201-1595
Contact: Kirsten Lyke, M.D.    410-706-6156    klyke@medicine.umaryland.edu   
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: VRC Clinic    301-451-8715    vaccines@nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Julie E Ledgerwood, D.O. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier: NCT02015091     History of Changes
Other Study ID Numbers: 140035, 14-I-0035
Study First Received: December 18, 2013
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Healthy Subjects
Vaccine-Mediated Protection
Immunogenicity
Sporozoites
Parasitemia

Additional relevant MeSH terms:
Malaria
Parasitemia
Protozoan Infections
Parasitic Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on July 28, 2014