Trial of a Falciparum Malaria Protein (FMP012), E. Coli-expressed PfCelTOS, in Healthy Malaria-Naive Adults

May 12, 2021 updated by: U.S. Army Medical Research and Development Command

Phase 1 Study With the Vaccine Candidate Plasmodium Falciparum Malaria Protein (FMP012), an E.Coli-expressed Cell-Traversal Protein, Administered Intramuscularly in Healthy Malaria-Naive Adults

Malaria has remained a major concern for the US military. During World War II, malaria was the leading cause of disease and non-battle injury with 500-700 men infected per day, resulting in 24,000 malaria-related casualties.(10) Currently, the methods used for protecting troops against malaria are insecticidal nets, clothing, and antimalarial treatment. To be effective, these methods must be self-administered and be used consistently, often unattainable in field or combat situations. The United States Army Medical Research and Development Command (USAMRMC), through the United States Army Medical Materiel Development Activity (USAMMDA) and the Walter Reed Army Institute of Research (WRAIR) are actively pursuing the development of an effective vaccine against P. falciparum malaria; development of such a vaccine is a high priority for the US military and other individuals who travel to endemic regions, and is equally important to populations residing in those areas.

A Phase 1 study using FMP012, a recombinant E.coli expressed malaria protein (CelTOS) vaccine will

  1. assess the safety and reactogenicity of candidate P. falciparum malaria vaccine FMP012/GLA-SE

    Secondary:

  2. measure the humoral immune response to FMP012/GLA-SE using enzyme-linked immunosorbent assay (ELISA)
  3. assess the protective efficacy of FMP012/GLA-SE against a P. falciparum sporozoite challenge.

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

Single center, non-randomized, open label, dose escalation Phase 1study with sporozoite challenge. The antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant produced by the Infectious Disease Research Institute (IDRI). This is a first-in-human study of FMP012. Thirty subjects, divided into 3 groups (10 subjects per group), will receive 3 doses of the FMP012/GLA-SE vaccine. Group 1 will receive 10 µg of FMP012 formulated with 2 µg GLA-SE adjuvant and Group 2 will receive 10 µg of FMP012 formulated with 5 µg GLA-SE adjuvant. Group 3 will receive 50 µg of FMP012 formulated with either 5 µg GLA-SE adjuvant (Group 3a) or 2 µg GLA-SE adjuvant (Group 3b). Determination of whether to proceed with Group 3a or Group 3b will be made by the principal investigator (PI) and the independent medical monitor after the second vaccination dose in Group 2 has been completed, based on predefined safety and group hold criteria in this protocol. There will be a staggered start for Group 1 and Group 2 separated by a minimum of 14 days. Group 3a or Group 3b will start vaccinations 2 weeks after the second vaccination for Group 2. The first and second vaccination doses in each group will be separated by 28 days and all groups will receive the third vaccination dose on the same day. The second and third vaccination doses in Group 1 will be separated by 84 days, Group 2 by 70 days, and Group 3 by 28 days. Six non-immunized infectivity control subjects will be enrolled prior to the challenge phase. All subjects from the Vaccination Group and Infectivity Control Group will participate in the primary malaria sporozoite challenge and will be required to stay at a hotel for evaluation for a maximum of 10 nights starting 9 days after the challenge. A directly monitored, sequentially allocated, open-label oral regimen of chloroquine or artemether/lumefantrine will be administered to all parasitemic subjects.

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.
36

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

  • United States
    • Maryland
      • Silver Spring, Maryland, United States, 20910
        • Clinical Trials Center, WRAIR

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 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

  • Healthy adults (male or non-pregnant, non-lactating female) 18 to 50 years of age at the time of screening
  • If the subject is female,
  • Non-childbearing potential , abstinent or using adequate contraceptive precautions during this study and must agree to continue such precautions until three months after challenge
  • A negative pregnancy test at the time of enrollment
  • Free of significant health problems as established by medical history, laboratory, and clinical examination before entering the study
  • Low cardiac risk factors
  • Available to participate and reachable by phone for duration of study (approximately 8 months)
  • No plans to travel to outside the Washington DC area between the day of challenge and either completion of treatment course (post-challenge) or, if subject remains uninfected, 28 days post-challenge
  • No plans to travel to a malaria endemic area during the course of the study
  • Written informed consent must be obtained from the subject before screening procedures
  • Subjects must score at least 80% correct on a multiple-choice quiz that assesses their understanding of this study
  • Active duty military must obtain approval from his or her supervisor

Exclusion Criteria:

  • History of malaria infection
  • History of travel to P. falciparum endemic areas in the 3 months prior to day of first vaccination or day of challenge
  • History of receiving a malaria vaccine
  • Receipt of any licensed vaccine within 7 days prior to first vaccination
  • History of receipt of malaria prophylaxis during the 2 months prior to day of first vaccination or day of challenge
  • History of use of any drugs with significant antimalarial activity during the course of the study period
  • Prior receipt of any vaccine containing either QS-21, MPL or GLA-SE in the previous 5 years (including Cervarix®, GSK)
  • Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine or planned use during the study period.
  • Any history of allergic reaction or anaphylaxis to previous vaccination
  • Allergy to kanamycin, nickel, or imidazole Pregnant or lactating female at screening or plans to become pregnant or breastfeed from the time of enrollment until three months after challenge
  • Allergy to antimalarial drugs or use of medications known to interact with both CQ and artemether/lumefantrine
  • Significant (eg, systemic) hypersensitivity reactions to mosquito bites
  • History of sickle cell disease
  • History of psoriasis or porphyria
  • History of splenectomy
  • Any confirmed or suspected immunodeficiency, including HIV infection
  • Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune-modifying drugs within six months of vaccination
  • Inhaled and topical steroids are allowed
  • A family history of congenital or hereditary immunodeficiency
  • Acute or chronic, clinically significant, pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by history, physical examination, or laboratory evaluation
  • Chronic or active neurologic disease including seizure disorder and chronic migraine headaches
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or any planned administration during the study period
  • Any abnormal baseline laboratory screening tests listed below (normal values are defined in the adverse event section of this protocol):
  • Seropositive for HIV or Hepatitis C virus or HBsAg positive
  • Hepatomegaly, right upper quadrant abdominal pain or tenderness
  • An abnormal baseline screening EKG.
  • Suspected or known current alcohol or drug abuse as determined from the medical history or by physical examination
  • Any other significant finding that in the opinion of the PI would increase the risk of having an adverse outcome from participating in this study

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

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: Group 1: 10 ug FMP012 with 2 ug GLA-SE
Single center, non-randomized, open label, dose escalation Phase 1 study with sporozoite challenge. The antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion. This is a first-in-human study of FMP012. 30 subjects, divided into 3 groups, will receive 3 doses of the FMP012/GLA-SE vaccine. Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant
Biological: Group 1: 10 ug FMP012 with 2 ug GLA-SE
Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant
Experimental: Group 2: 10 ug FMP012 with 5 ug GLA-SE
Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant
Biological: Group 2: 10 ug FMP012 with 5 ug GLA-SE
E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant
Experimental: Group 3: 50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE
Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant
Biological: 50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE
E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant
Other: Control group-Challenged Only
Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant
Other: Controlled group-Challenged Only: no vaccination
The control group participated in the primary malaria sporozoite challenge.E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant

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
Number of Participants With Solicited or Unsolicited Symptoms Reporting During the Post-vaccination Period
Time Frame: From vaccination day through 7 days post vaccination (for all three doses)
Number of participants for each dose (1 through 3) that experienced any symptom, general solicited symptoms, and local solicited symptoms
From vaccination day through 7 days post vaccination (for all three doses)
Number of Participants With Solicited or Unsolicited Symptoms Reporting During the Post-vaccination Period
Time Frame: From vaccination day through 7 days post vaccination for each does (1-3)
Incidence of erythema and pain (solicited local symptoms) reported after each dose (1-3) of vaccination. Results for groups 1, 2 and 3 only as control group did not receive any vaccinations and only participated in the malaria challenge portion of the study.
From vaccination day through 7 days post vaccination for each does (1-3)
Subjects Reporting the Occurrence of Unsolicited Adverse Events Related to Vaccination
Time Frame: 28 days after each vaccination
Number of participants with at lease one administered dose presenting with at least one specified symptom within 28 days after vaccination
28 days after each vaccination

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
Humoral Immune Response to FMP012/GLA-SE
Time Frame: Up to 1 year

Seroconversion was defined as a post-second vaccination titer (serum dilution of 1:100) that is 3 standard deviations higher than the average of the negative or pre-vaccination serum measured using enzyme-linked immunosorbent assay (ELISA). Values reported as "below the detection limit" were given a value of 50 units. The safety population was used for immunogenicity analysis. Only subjects who received vaccinations or were challenged were included in the analysis of immunogenicity. Subjects who withdrew from the study had data collected to the point of withdraw.

Geometric mean titers (GMT) were obtained by first calculating the mean and 95% confidence intervals for log-transformed values of the ELISA results, followed by exponentiation of the values. Among those vaccinated, all values were below the detection limit until post-dose II.
Up to 1 year
Time to Onset of Parasitemia Following Sporozoite Challenge
Time Frame: Up to 1 year
Protective Efficacy of FMP012/GLA-SE Measured against a P falciparum sporozoite challenge. Vaccinated subjects were compared to infectivity controls to assess for delayed onset of parasitemia. Time of onset of parasitemia was based on the date of sporozoite challenge to the date of first positive blood smear detection.
Up to 1 year

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.
United States Agency for International Development (USAID)
IDRI

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: Jessica J. Cowden, MD, Walter Reed Army Institute of Research (WRAIR)

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 (Actual)

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.
February 1, 2012

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.
October 1, 2012

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, 2012

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).
February 9, 2012

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.
February 27, 2012

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.
February 28, 2012

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.
June 8, 2021

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.
May 12, 2021

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.
May 1, 2021

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.
  • S-11-21
  • IND 014962 (Other Identifier: WRAIR)

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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