Back to results

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

Primary Purpose

Malaria

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Group 1: 10 ug FMP012 with 2 ug GLA-SE

Group 2: 10 ug FMP012 with 5 ug GLA-SE

50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE

Controlled group-Challenged Only: no vaccination

About this trial

This is an interventional treatment trial for Malaria focused on measuring Interference of malaria infection

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Clinical Trials Center, WRAIR

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Other

Arm Label

Group 1: 10 ug FMP012 with 2 ug GLA-SE

Group 2: 10 ug FMP012 with 5 ug GLA-SE

Group 3: 50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE

Control group-Challenged Only

Arm Description

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/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant

Outcomes

Primary Outcome Measures

Number of Participants With Solicited or Unsolicited Symptoms Reporting During the Post-vaccination Period

Number of participants for each dose (1 through 3) that experienced any symptom, general solicited symptoms, and local solicited symptoms

Number of Participants With Solicited or Unsolicited Symptoms Reporting During the Post-vaccination Period

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.

Subjects Reporting the Occurrence of Unsolicited Adverse Events Related to Vaccination

Number of participants with at lease one administered dose presenting with at least one specified symptom within 28 days after vaccination

Secondary Outcome Measures

Humoral Immune Response to FMP012/GLA-SE

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.

Time to Onset of Parasitemia Following Sporozoite Challenge

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.

Full Information

NCT ID

NCT01540474

First Posted

February 9, 2012

Last Updated

May 12, 2021

Sponsor

U.S. Army Medical Research and Development Command

Collaborators

United States Agency for International Development (USAID), Access to Advanced Health Institute (AAHI)

1. Study Identification

Unique Protocol Identification Number

NCT01540474

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

February 2012 (Actual)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

U.S. Army Medical Research and Development Command

Collaborators

United States Agency for International Development (USAID), Access to Advanced Health Institute (AAHI)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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 assess the safety and reactogenicity of candidate P. falciparum malaria vaccine FMP012/GLA-SE Secondary: measure the humoral immune response to FMP012/GLA-SE using enzyme-linked immunosorbent assay (ELISA) assess the protective efficacy of FMP012/GLA-SE against a P. falciparum sporozoite challenge.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

Keywords

Interference of malaria infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: 10 ug FMP012 with 2 ug GLA-SE

Arm Type

Experimental

Arm Description

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

Arm Title

Group 2: 10 ug FMP012 with 5 ug GLA-SE

Arm Type

Experimental

Arm Description

Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant

Arm Title

Group 3: 50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE

Arm Type

Experimental

Arm Description

Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant

Arm Title

Control group-Challenged Only

Arm Type

Other

Arm Description

Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant

Intervention Type

Biological

Intervention Name(s)

Group 1: 10 ug FMP012 with 2 ug GLA-SE

Intervention Description

Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant

Intervention Type

Biological

Intervention Name(s)

Group 2: 10 ug FMP012 with 5 ug GLA-SE

Intervention Description

E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant

Intervention Type

Biological

Intervention Name(s)

50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE

Intervention Description

E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant

Intervention Type

Other

Intervention Name(s)

Controlled group-Challenged Only: no vaccination

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With Solicited or Unsolicited Symptoms Reporting During the Post-vaccination Period

Description

Number of participants for each dose (1 through 3) that experienced any symptom, general solicited symptoms, and local solicited symptoms

Time Frame

From vaccination day through 7 days post vaccination (for all three doses)

Title

Number of Participants With Solicited or Unsolicited Symptoms Reporting During the Post-vaccination Period

Description

Time Frame

From vaccination day through 7 days post vaccination for each does (1-3)

Title

Subjects Reporting the Occurrence of Unsolicited Adverse Events Related to Vaccination

Description

Number of participants with at lease one administered dose presenting with at least one specified symptom within 28 days after vaccination

Time Frame

28 days after each vaccination

Secondary Outcome Measure Information:

Title

Humoral Immune Response to FMP012/GLA-SE

Description

Time Frame

Up to 1 year

Title

Time to Onset of Parasitemia Following Sporozoite Challenge

Description

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jessica J. Cowden, MD

Organizational Affiliation

Walter Reed Army Institute of Research (WRAIR)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Clinical Trials Center, WRAIR

City

Silver Spring

State/Province

Maryland

ZIP/Postal Code

20910

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs