Immunization of Human Volunteers With P. Vivax Irradiated Sporozoites (SPZ-Irrad)

This study is not yet open for participant recruitment.

Verified April 2012 by Malaria Vaccine and Drug Development Center

Sponsor:

Collaborators:

National Heart, Lung, and Blood Institute (NHLBI)

Asoclinic Laboratorio de Inmunología

Information provided by (Responsible Party):

Socrates Herrera Valencia, Malaria Vaccine and Drug Development Center

ClinicalTrials.gov Identifier:

NCT01082341

First received: March 5, 2010

Last updated: April 23, 2012

Last verified: April 2012

History of Changes

Purpose

It is possible to safely protect human volunteers immunized with P. vivax irradiated sporozoites from P. vivax challenge with live sporozoites.

Condition	Intervention	Phase
Malaria	Biological: Immunization with P. vivax irradiated sporozoites	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Phase 1 and Phase 2a Clinical Trial:Immunization of Human Volunteers With P. Vivax Irradiated Sporozoites

Resource links provided by NLM:

MedlinePlus related topics: Malaria

U.S. FDA Resources

Further study details as provided by Malaria Vaccine and Drug Development Center:

Primary Outcome Measures:

Three groups are considered to be intervened. Experimental, Control and Fy(-) groups. Comparison will be done between E and C groups for protective efficacy. For immune response tests E vs Fy(-),E vs Fy(-), and Fy(-) vs C, pairs will be compared. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The number of subjects reporting any AEs, the occurrence of specifics AEs, and discontinuation due to AEs will be tabulated. Frequency of AEs will be cross-tabulated by group for each immunization session [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	27
Study Start Date:	June 2012
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Fy(+) 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites	Biological: Immunization with P. vivax irradiated sporozoites Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials. Other Name: P. vivax irradiated sporozoites vaccine
Active Comparator: Fy(+) control Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites.	Biological: Immunization with P. vivax irradiated sporozoites Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials. Other Name: P. vivax irradiated sporozoites vaccine
Active Comparator: Fy(-) Six Fy(-) volunteers will be exposed to infective mosquito bites.	Biological: Immunization with P. vivax irradiated sporozoites Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials. Other Name: P. vivax irradiated sporozoites vaccine
No Intervention: P. vivax infected donor In this step we will identify malaria infected patients that will be requested to provide parasitized blood for mosquito infection. Volunteers will be recruited from among the patients who present with active P. vivax infection to the laboratory for malaria diagnose	Biological: Immunization with P. vivax irradiated sporozoites Anopheles albimanus mosquitoes will be infected by artificial membrane feeding using blood from P. vivax infected donors. Once mosquitoes are positive will be irradiated at 15000 cGy and kept in boxes until use. 14 Fy(+) human volunteers in the experimental group will be immunized with 1,000-2,000 P. vivax irrad-spz bites. Seven Fy(+) volunteers in the control group will be exposed to non-infected mosquito bites. Six Fy(-) volunteers will be exposed to infective mosquito bites. For the challenge both the immunized and control groups will be exposed to 3 ± 1 infective mosquito bites. Volunteers will be closely monitored post infection and will be treated with antimalarials. Other Name: P. vivax irradiated sporozoites vaccine

Detailed Description:

Title: Phase 1 and Phase 2a Clinical Trial: Immunization of human volunteers with P. vivax irr-spz. (Short name: Irrad-SPZ) Population 27 healthy adult volunteers, males and non-pregnant females, between 18-45 years of age, who fulfill inclusion/exclusion criteria (described below) as determined by clinical history and serological tests. Approximately 20 parasitized blood-donor volunteers will be required to infected Anopheles mosquitoes which will be used to immunize volunteers with a total of 1000-1500 infected mosquitoes, during 8-10 months. Afterwards challenge to prove protection.

Number of Sites: 2 Study Duration: 2 years. Subject Duration : Step1: 1-2 hours to blood donors; Step 2 and 3: 2 years to immunized volunteers Objectives Primary

• To assess the safety and protective efficacy of P. vivax irradiated sporozoite vaccination.

Secondary

To determine the immune responses and duration elicited by the P. vivax challenge in human Fy(+) volunteers previously immunized with irr-spz, as compared with non-immunized human volunteers.
To determine the immune responses and duration elicited by irr-spz immunization scheme in human Fy(+) volunteers; comparing it with the same immunization scheme with non irr-spz in Fy(-) participants, and also with controls exposed to the same mosquito bite scheme as that of immunization but using mosquitoes without parasite infection.
To study new antigens potentially useful to induce pre-erythrocytic protection against P. vivax malaria infection

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Healthy 18 to 45 years old man or non-pregnant women.
- To have the capacity to sign an informed consent in a free and voluntary way.
- Have an acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process.
- Obligatory use of adequate contra-conceptive method from beginning of recruitment and screening time up to three months after last immunization
- Do not have chronic or acute diseases. These conditions will be determined by clinical history, physical exam and laboratory tests.
- To accept not traveling to malaria endemic areas during the clinical trial should
- To have telephone at home or mobile phone that permit permanent contact for follow up
- He (she) manifest that is willing to participated during both steps of the clinical trial.

Exclusion Criteria:

Volunteers with less than 18 old year or more than 45 old years.
Pregnant and suckling women will be excluded. Pregnancy will be determined both by interview, and by serum B-subunit chorionic gonadotrophin testing.
History of moderate or severe insect, or food allergies.
G-6PD deficiency or any Hb genetic defect (for example; sickle cell disease)
Previous malaria infection demonstrated by think smear, PCR or specific antimalarial antibodies.
If the subject has previously participated in a malarial vaccine trial.
Clinical record of allergies to drug or insect bites.
Symptoms, signs or data from laboratory test that suggests to the physician any systemic disorder like renal, hepatic, cardiovascular, pulmonary, psychiatric disorders or other illnesses that could interfere with results of clinical trial or could compromise the health of the volunteer.
To have antibodies against hepatitis C, VIH, or hepatitis B superficial antigen and/or hepatitis B core antibodies.
To have any abnormality in the parameters assessed by blood laboratory tests. Base-line values will be established before initiation of the clinical trial.
Presence or history of an auto-immune disease such as; Asthma, lupus, rheumatoid arthritis, Graves's disease, Hashimoto tyroiditis, and others.
History of surgical removal of the spleen (splenectomy).
Volunteer with medical treatment known to alter the immune system before 3 months to recruitment, such as; cortico-steroids, chemotherapeutic agents, fludarabine, cyclosporine, tacrolimus, mycophenolate mofetil, rapamycine, ATG, alemtuzumab.
Alcoholism or drug abuse that may interfere with social relationship of individual.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082341

Contacts

Contact: Socrates Herrera, MD

(072) 5216228

sherrera@inmuno.org

Locations

Colombia
Malaria Vaccine of Develepmente Center	Not yet recruiting
Cali, Valle, Colombia
Contact: Socrates Herrera, MD (072) 5216228 sherrera@inmuno.org
Contact: Myriam Arevalo, PhD (072) 5216228 Marevalo@inmuno.org
Principal Investigator: Socrates Herrera, MD
Sub-Investigator: Myriam Arevalo, PhD
Sub-Investigator: Yesid Solarte, Entomologist
Sub-Investigator: Ernesto Martinez, MD, PHD
Sub-Investigator: Aurelio Angulo, MD, PhD

Sponsors and Collaborators

Malaria Vaccine and Drug Development Center

National Heart, Lung, and Blood Institute (NHLBI)

Asoclinic Laboratorio de Inmunología

Investigators

Principal Investigator:

Socrates Herrera, MD

Malaria Vaccine Develepment Center

More Information

Additional Information:

www.inmuno.org This link exits the ClinicalTrials.gov site

Publications:

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Valderrama-Aguirre A, Quintero G, Gomez A, Castellanos A, Perez Y, Mendez F, Arevalo-Herrera M, Herrera S. Antigenicity, immunogenicity, and protective efficacy of Plasmodium vivax MSP1 PV200l: a potential malaria vaccine subunit. Am J Trop Med Hyg. 2005 Nov;73(5 Suppl):16-24.

Arevalo-Herrera M, Castellanos A, Yazdani SS, Shakri AR, Chitnis CE, Dominik R, Herrera S. Immunogenicity and protective efficacy of recombinant vaccine based on the receptor-binding domain of the Plasmodium vivax Duffy binding protein in Aotus monkeys. Am J Trop Med Hyg. 2005 Nov;73(5 Suppl):25-31.

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Responsible Party:	Socrates Herrera Valencia, Director, Malaria Vaccine and Drug Development Center
ClinicalTrials.gov Identifier:	NCT01082341 History of Changes
Other Study ID Numbers:	MVDC-2008-005, SPZ IRR HUMAN, 5R01HL086488-02
Study First Received:	March 5, 2010
Last Updated:	April 23, 2012
Health Authority:	Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

Keywords provided by Malaria Vaccine and Drug Development Center:

GCP Good Clinical Practice
IFAT Indirect Immunofluorescence antibody test
MFA Membrane Feeding Assay
N Number (typically refers to subjects)
RBC Red Blood Cells

SOP Standard Operating Procedure
TBS Thick blood smear
P. Vivax
irradiated sporozoite vaccination.

Additional relevant MeSH terms:

Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on May 16, 2013

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