Phase I/II Trial of a Malaria Vaccine in Adults Living in the United States of America

Study Overview
=================
Brief Summary
-----------------
Phase I/II Trial of a Malaria Vaccine, FMP011/AS01B, in Adults Living in the United States of America.

Detailed Description
-----------------
Controlled challenge, Phase I/IIa WRAIR study. Healthy, malaria-naive adults aged 18 - 50 years. 2 groups, 5 subjects in group A (10µg dose) and 13 subjects in group B(50µg dose). Control: none for immunization phase; infectivity controls for challenge and rechallenge phases. Six infectivity controls per day of challenge will be enrolled for the challenge phases, with 3 alternates available for challenge if needed. Vaccination schedule of 0, 1 months. Challenge of up to 13 subjects in Group B. Contingent upon short term efficacy, rechallenge of initially protected subjects 6 months (+/- 2 months) after second dose of vaccine. Self-contained study. Duration of the study, per subject: approximately 15 months (screening, enrollment, vaccination, challenge and rechallenge). Data collection will be by done onsite.

Official Title
-----------------
A Phase I/IIa Controlled Study of the Safety, Immunogenicity and Preliminary Efficacy of FMP011/AS01B Candidate Malaria Vaccine in Malaria-naive Adults Living in the United States

Conditions
-----------------
Plasmodium Falciparum Malaria

Intervention / Treatment
-----------------
* Biological: Falciparum Malaria Protein 11 with AS01B adjuvant.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A male or non-pregnant female 18 to 50 years of age (inclusive) at the time of screening. Written informed consent obtained from the subject before screening procedures. Free of obvious health problems as established by medical history and clinical examination before entering into the study.* Available to participate for duration of study (approximately 15 months). If the subject is female, she must be currently using birth control, must be surgically sterilized, or must be at least 1-year post menopausal. Pass a comprehension assessment test. Exclusion Criteria: Prior receipt of an investigational malaria vaccine. Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 28 days preceding the first dose of study vaccine, or planned use during the study period. Administration of chronic immunosuppressants or other immune modifying drugs within six months of vaccination. Chronic use of antibiotics with anti-malarial effects. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s). History of use of anti-malarial medication within 60 days prior to vaccination. Any history of malaria. Known exposure to malaria within the previous 12 months. Planned travel to malarious areas during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Chronic or active neurologic disease including seizures, but not including a single febrile seizure as a child. History of splenectomy. Acute disease at the time of enrollment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Personal history of autoimmune disease or subjects who describe a first-degree relative with clearly documented autoimmune disease. Seropositive for hepatitis B surface antigen. Seropositive for Hepatitis C virus (antibodies to HCV). Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned. administration during the study period Pregnant or lactating female. Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV. Chronic or active intravenous drug use. History of severe reactions to mosquito bites as defined as anaphylaxis. Female who intends to become pregnant during the study. Any history of anaphylaxis in reaction to vaccination. A clinical history of sickle cell disease or sickle cell trait. Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10ug dose FMP011<br>Falciparum Malaria Protein 11 with AS01B adjuvant | Biological: Falciparum Malaria Protein 11 with AS01B adjuvant.<br>* malaria experimental vaccine<br>|
| Experimental: 50ug dose FMP011<br>Falciparum Malaria Protein 11 with AS01B adjuvant | Biological: Falciparum Malaria Protein 11 with AS01B adjuvant.<br>* malaria experimental vaccine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Most Frequently Reported Adverse Events and Grade | An AE was defined as any reaction, side effect, or untoward event that occurred during the course of the trial whether or not the event was considered related to the study drug or clinically significant. Grade 1: Mild Grade 2: Moderate Grade 3: Severe | 30 days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-LSA-1 Antibody Response in Titer Units on Days 0, 28, 42, and 84 | Anti-LSA-1 Antibody Response in Titer Units on Days 0, 28, 42, and 84 | Days 0, 28, 42, and 84 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, Phase I/II, Malaria, Liver Stage Antigen -1, Falciparum Malaria Protein -11, AS01B, adjuvant