FMP2.1/AS02A: Rabies Vaccine Malaria-Experienced Adults in Bandiagara, Mali

April 25, 2017 updated by: U.S. Army Medical Research and Development Command

Double Blind Randomized, Controlled Phase 1 Dose Escalation Trial to Evaluate the Safety and Immunogenicity of the WRAIR AMA1 Malaria Antigen (FMP2.1) Adjuvanted in GSK's AS02A Versus Rabies Vaccine in Malaria-experienced Adults in Bandiagara, Mali

Malaria is a disease that affects many people in Africa and in Mali. It is caused by germs that are spread by mosquito bites. This study will look at the safety, effectiveness, and best dose of an experimental malaria vaccine in people who are regularly exposed to malaria. Study participants will be 60 adults, 18-55 years old, who live in Bandiagara, Mali. Volunteers will get either 3 full doses of the experimental malaria vaccine, 3 half doses of the malaria vaccine, or a rabies vaccine that has been approved in Mali. (Rabies is an infection of the brain that usually causes death, and can be caught from being bitten by infected dogs or bats.) The 3 vaccinations will be given by injection into the upper arm 30 days apart. Volunteers will be enrolled in the study for approximately 12 months after the first vaccination. Volunteers will have 14 blood samples collected during the study for testing to make sure that the vaccine is not harmful and to measure the effect of the vaccine.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The primary objective of this study is to evaluate the safety and reactogenicity of two dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Secondary objectives are to: (1) measure the magnitude and duration of antibody response to FMP2.1; (2) measure cellular immune responses to FMP2.1 at baseline and after immunization; (3) measure the inhibition of parasite growth by the in vitro GIA; and (4) determine the specificity of the antibodies to diverse AMA1 genotypes in addition to 3D7, by measuring by ELISA, and GIA on parasites with typed AMA1. A double-blind controlled dose escalation trial will allow assessment of vaccine safety in each of three groups, one group each to receive medium and full dose levels of the experimental vaccine, and one group to receive the comparator vaccine. Thirty adults will be randomized to receive the medium dose level of FMP2.1 (n=20) or rabies vaccine (n=10) and thirty to receive the full dose level of FMP2.1 (n=20) or rabies vaccine (n=10). The division of the rabies group into two groups of ten is done to maintain blinding at each immunization time point, and all participants who receive the rabies vaccine will be analyzed as a single group. The sample size of the groups, however, will not allow detection of anything other than very large differences in the occurrence of adverse events among the three groups. The advantage of double blinding is to remove the potential for investigator and participant prejudgment about the effects of the vaccines in the reporting of adverse events.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Bamako, Mali
        • University of Bamako, Malaria Research and Training Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. A male or non-pregnant female aged 18-55 years inclusive at the time of screening
  2. For women, willingness not to become pregnant until 1 month after the last immunization (pre-menopausal female participants will be referred to the local family planning clinic in Bandiagara, which offers several means of contraception that are approved and recommended by the Malian Ministry of Health)
  3. Separate written informed consent obtained from the participant before screening and study start, respectively
  4. Available and willing to participate in follow-up for the duration of study (12 months)

Exclusion Criteria:

  1. Previous vaccination with any investigational vaccine or with any rabies vaccine
  2. Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization, or planned use up to 30 days after the third immunization
  3. Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first immunization. This will include any dose level of oral steroids or inhaled steroids, but not topical steroids
  4. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first study immunization with the exception of tetanus toxoid
  5. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
  6. Any confirmed or suspected autoimmune disease
  7. History of allergic reactions or anaphylaxis to immunizations or to any vaccine component
  8. History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care
  9. History of allergy to tetracycline, doxycycline, nickel, Imidazole, chicken eggs, processed bovine gelatin, chicken protein, neomycin, or amphotericin B
  10. History of splenectomy
  11. Serum ALT >/=43 IU/L
  12. Serum creatinine level >113 µmol /L for males and 70 µmol /L for females
  13. Hgb <11 g/dL for males and <10 g/dL for females
  14. WBC <4.0 x 1000/cubic mm or >13 x 1000/cubic mm
  15. Absolute lymphocyte count </=1.4 x 1000 /µl
  16. Thrombocytopenia < 108,000/µl
  17. More than trace protein, more than trace hemoglobin or positive glucose in urine
  18. Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period
  19. Suspected or known current alcohol or illicit drug abuse
  20. Pregnancy or positive urine beta-HCG on the day of or prior to immunization
  21. Breastfeeding
  22. Simultaneous participation in any other interventional clinical trial
  23. Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition, or any other findings that in the opinion of the Principal Investigator (PI) may increase the risk of participating in the study
  24. Other condition that in the opinion of the PI would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Cohort 1: 25ug FMP2.1 / AS02A
20 subject to receive 25ug of FMP2.1 vaccine in 0.25mL of GSK Biologicals' adjuvant AS02A
Biological: FMP2.1/AS02A
FMP2.1 in GSK Biologicals' AS02A
EXPERIMENTAL: Cohort 2: 50ug FMP2.1 / AS02A
20 subjects to receive 50ug of FMP2.1 vaccine in 0.5mL of GSK Biologicals' adjuvant AS02A
Biological: FMP2.1/AS02A
FMP2.1 in GSK Biologicals' AS02A
ACTIVE_COMPARATOR: Cohorts 1 and 2: Rabies vaccine (RabAvert)

20 subjects to receive Rabies vaccine (RabAvert). 10 subjects from Cohort 1 and 10 subjects from Cohort 2

Rabies vaccine (RabAvert): RabAvert Rabies vaccine
Biological: FMP2.1/AS02A
FMP2.1 in GSK Biologicals' AS02A
Biological: Rabies vaccine (RabAvert)
RabAvert Rabies vaccine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and Reactogenicity (SAEs and AEs)
Time Frame: 12 months
The primary objective was to evaluate the safety and reactogenicity of 2 dose levels of WRAIR's AMA1 malaria antigen (FMP2.1) adjuvanted in GlaxoSmithKline Biologicals' (GSK) AS02A compared to rabies vaccine in malaria-experienced Malian adults aged 18-55 years inclusive. Solicated AEs were recorded for the 7 day surveillance period after each vaccination. Unsolicited AEs were recorded for 30 days after each vaccination.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Antibody Response to FMP2.1 Over Time
Time Frame: 90 Days
Measurement of anti-AMA1 antibody titers over time
90 Days
Anti-AMA1 Log Antibody Titers Over Time
Time Frame: 90 Days
Summary of Anti-AMA1 Log Antibody titers on days 0, 14, 30, 44, 60, 74 and 90
90 Days
Geometric Mean Antibody Titers Over Time
Time Frame: 90 Days
Measurement of geometric mean antibody titers on days 0, 14, 30, 44, 60, 74 and 90
90 Days
Subjects With 2- and 4-fold Increases in Anti-FMP2.1 Antibody Levels Over Time
Time Frame: 90 Days
Proportion of Subjects with 2- and 4-fold increases in Anti-FMP2.1 Antibody levels on days 14, 30, 44, 60, 74 and 90
90 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
U.S. Army Medical Research and Development Command

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)
GlaxoSmithKline
University of Maryland
Walter Reed Army Institute of Research (WRAIR)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mahamadou A. Thera, M.D., University of Bamako
  • Principal Investigator: Chris V. Plowe, M.D., University of Maryland School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2004

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2005

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2006

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 6, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 6, 2006

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 10, 2006

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 24, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 04-031
  • N01AI085346-006 (NIH)
  • N01AI085346-005 (NIH)
  • N01AI085346-000 (NIH)
  • 102231 ( Malaria-037) (OTHER: GSK)
  • HSRRB A-12855 (OTHER: USAMRMC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Plan to share data with

National Institute of Allergy and Infectious Diseases (NIAID)

Walter Reed Army Institute of Research (WRAIR)

GlaxoSmithKline

University of Maryland

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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