Malaria Clinical Trial
Official title:
VRC 312: A Phase 1, Open-Label, Dose-Escalation Clinical Trial With Experimental Challenge to Evaluate Intravenous Administration of the PfSPZ Vaccine in Malaria-Naive Adults
Verified date | June 5, 2013 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Background:
- Malaria parasites are carried by mosquitoes, which spread the infection by biting
people. Currently, there is no effective malaria vaccine. However, studies show that
volunteers bitten many times by mosquitoes that carry weakened malaria parasites could
fight off getting sick with malaria when later exposed to normal malaria parasites.
Malaria parasites are weakened by exposing them to radiation when they are in the stage
of development called sporozoites . Only the mosquitoes are irradiated and study
volunteers are not exposed to radiation. The radiation stops the parasites from being
able to cause disease but still promote protection. For many years, it was not possible
to give these sporozoites to people as a vaccine since they could not be adequately
purified from the mosquito. Scientists have recently figured out how to produce and
isolate the weakened sporozoites so that they can be given in an injected vaccine. This
vaccine is known as the "PfSPZ vaccine".
- A malaria challenge will be used to test whether the vaccine will prevent infection. In
a malaria challenge, mosquitoes that have the malaria parasite will be allowed to bite a
participant's arm. In the event that the vaccine does not work, the malaria parasite
used for the challenge can be treated completely with common anti-malaria medications.
Participants will be treated immediately if they develop malaria symptoms.
Objectives:
- To test the safety and effectiveness of the PfSPZ vaccine.
Eligibility:
- Healthy volunteers between 18 to 45 years of age.
Design:
- Participants will be screened with a physical exam, medical history, and blood tests.
There will be five different groups of study participants, all of whom will be monitored
with frequent blood tests.
- Group 1 will have two vaccines with the lowest amount of the vaccine given 4 weeks
apart, with regular clinic visits up to 24 weeks after the second vaccine. This group
will not have a malaria challenge.
- Group 2 will have four or six vaccines given 4 weeks apart at a higher dose than group
1. A malaria challenge will be given about 3 weeks after the last vaccine. Follow-up
visits will continue through 24 weeks after the last vaccine.
- Group 3 will have four or six vaccines given 4 weeks apart at a higher dose than group
2. A malaria challenge will be given about 3 weeks after the last vaccination, as for
Group 2. Follow-up visits will continue through 24 weeks after last vaccine.
- Group 4 will have four or six vaccines given 4 weeks apart at a higher dose than group
3. A malaria challenge will be given about 3 weeks after the last vaccination. Follow up
visits will continue through 24 weeks after last vaccine.
- Group 5 will serve as a control group and will not receive the vaccine, but will have
the malaria challenge. Follow-up visits will continue through 8 weeks after the
challenge.
All participants from any group who receive a malaria challenge will be treated promptly for
malaria when it develops.
Status | Completed |
Enrollment | 64 |
Est. completion date | June 5, 2013 |
Est. primary completion date | June 5, 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 45 Years |
Eligibility |
- 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 challenge. 7. Agree 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 Groups 1, 2, 3 and 4 or BMI less than or equal to 40 for Group 5. LABORATORY CRITERIA WITHIN 56 DAYS PRIOR TO ENROLLMENT: 9. Hemoglobin greater than or equal to 11.2 g/dL for women; greater than or equal to 13.0 g/dL for men. 10. Differential and platelet count either within institutional normal range or accompanied by site physician approval. 11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 1.25 times upper limit of normal (ULN) for Groups 1, 2, 3 and 4 or less than or equal to 1.75 ULN for Group 5. 12. Serum creatinine less than or equal to upper limit of normal. 13. Negative for HIV infection. LABORATORY CRITERION DOCUMENTED ANY TIME PRIOR TO ENROLLMENT: 14. Negative sickle cell screening test. FEMALE-SPECIFIC CRITERIA: 15. Negative beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of childbearing potential. 16. 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. Screening EKG showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm (except isolated premature atrial contractions); left bundle branch block; or advanced (secondary or tertiary) A-V heart block. 6. Current use of systemic immunosuppressant pharmacotherapy. 7. History of a splenectomy, sickle cell disease or sickle cell trait. 8. Plan for major surgery between enrollment and challenge. 9. 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. 10. 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. 11. Personal beliefs that prohibit the receiving of vaccine product containing human serum albumin within the diluent. 12. Use or planned use of any drug with anti-malarial activity that would coincide with study vaccination or challenge. 13. History of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine. 14. Anticipated use of medications known to cause drug reactions with chloroquine or atovaquone-proguanil (Malarone) such as cimetidine, metoclopramide, antacids, and kaolin. 15. 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. 16. 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. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) | Sanaria Incorporated, U.S. Military Malaria Vaccine Program |
United States,
Breman JG. Eradicating malaria. Sci Prog. 2009;92(Pt 1):1-38. Review. — View Citation
Nussenzweig RS, Vanderberg J, Most H, Orton C. Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature. 1967 Oct 14;216(5111):160-2. — View Citation
Sachs J, Malaney P. The economic and social burden of malaria. Nature. 2002 Feb 7;415(6872):680-5. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The primary objectives of the study are related to the safety and tolerability of the vaccine at the 4 dosage levels when administered IV. | |||
Secondary | The secondary objectives are related to PfSPZ vaccine-mediated protection against Plasmodium falciparum (Pf) challenge at the 3 higher dosage levels. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04601714 -
Baseline Cohort Malaria Morbidity Study
|
||
Withdrawn |
NCT04020653 -
A Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria
|
Phase 2 | |
Terminated |
NCT04368910 -
Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria
|
Phase 3 | |
Completed |
NCT03641339 -
Defining Skin Immunity of a Bite of Key Insect Vectors in Humans
|
N/A | |
Completed |
NCT02544048 -
Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults
|
||
Completed |
NCT00527163 -
Role of Nitric Oxide in Malaria
|
||
Not yet recruiting |
NCT05934318 -
L-ArGinine to pRevent advErse prEgnancy Outcomes (AGREE)
|
N/A | |
Active, not recruiting |
NCT04704674 -
Community Dynamics of Malaria Transmission in Humans and Mosquitoes in Fleh-la and Marshansue, Salala District, Bong County, Liberia
|
||
Completed |
NCT03276962 -
Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or Without Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age
|
Phase 2 | |
Completed |
NCT04966871 -
Safety, Tolerability and Efficacy of PfSPZ Vaccine Against Heterologous CHMI in US Malaria naïve Adults
|
Phase 1 | |
Completed |
NCT00289185 -
Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants
|
Phase 2 | |
Recruiting |
NCT03937817 -
Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
|
||
Active, not recruiting |
NCT06153862 -
Africa Ready Malaria Screening
|
N/A | |
Completed |
NCT04545905 -
Antenatal Care as a Platform for Malaria Surveillance: Utilizing Community Prevalence Measures From the New Nets Project to Validate ANC Surveillance of Malaria in Burkina Faso
|
||
Recruiting |
NCT06278181 -
Diabetes, Metabolic Syndrome and Risk of Malaria in Cameroon
|
||
Completed |
NCT02909712 -
Cardiac Safety of Dihydroartemisinin-Piperaquine Amongst Pregnant Women in Tanzania
|
Phase 2 | |
Withdrawn |
NCT02793414 -
Diagnostic Utility of Volatile Organic Compounds in Human Breath for Acute Clinical Malaria in Ethiopia
|
||
Withdrawn |
NCT02793388 -
A Trial on Supervised Primaquine Use in Ethiopia
|
Phase 4 | |
Completed |
NCT02793622 -
Prevention of Malaria in HIV-uninfected Pregnant Women and Infants
|
Phase 3 | |
Completed |
NCT02527005 -
A Comparative Study of Azithromycin and S-P as Prophylaxis in Pregnant HIV+ Patients
|
Phase 1 |