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

A Phase I/IIa Controlled Study of the Safety, Immunogenicity and Preliminary Efficacy of FMP011/AS02A Candidate Malaria Vaccine in Malaria-naive Adults Living in the United States

Phase I/II Trial of a Malaria Vaccine, FMP011/AS01B, in Adults Living in the United States of America.

Study Overview

• Status: Completed
• Conditions: Malaria; Plasmodium Falciparum Malaria
• Intervention / Treatment: Biological: Falciparum Malaria Protein 11 with AS02A adjuvant

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 15 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 15 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 at the site.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10µg dose FMP011; Falciparum Malaria Protein 11 with AS02A adjuvant	Biological: Falciparum Malaria Protein 11 with AS02A adjuvant; vaccine
Experimental: 50µg dose FMP011; Falciparum Malaria Protein 11 with AS02A adjuvant	Biological: Falciparum Malaria Protein 11 with AS02A adjuvant; vaccine

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 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	Anti-LSA-1 Antibody Response in Titer Units on days 0, 28, 42 and 84	days 0, 28, 42 (challenge day) and 84

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: GlaxoSmithKline; Walter Reed Army Institute of Research (WRAIR); The PATH Malaria Vaccine Initiative (MVI)
• Investigators: Principal Investigator: James F Cummings, MD, Walter Reed Army Institute of Research (WRAIR)

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: April 6, 2006
• First Submitted That Met QC Criteria: April 6, 2006
• First Posted (Estimate): April 10, 2006

Study Record Updates

• Last Update Posted (Actual): November 26, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Malaria; Vaccine; adjuvant; Liver Stage Antigen-1; Falciparum Malaria Protein-11; AS02A
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum
• Other Study ID Numbers: WRAIR 1249; HSRRB A-13732 (Other Identifier: USAMRMC)