Plasmodium Falciparum MalariaPhase 2NCT00460525

Phase II AMA-1 Malaria Vaccine FMP2.1/AS02A Trial in Mali

A Phase 2 study testing FMP2.1/AS02A and Rabies Vaccine in people with Plasmodium Falciparum Malaria, run by U.S. Army Medical Research and Development Command at 1 site in Mali.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 1 year to 6 yearsHealthy volunteers can take part
Conditions the study is for: Plasmodium Falciparum Malaria
What is being tested?: FMP2.1/AS02A and Rabies Vaccine
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 400 participants
Where: 1 siteMali
Study dates: May 2007to Jul 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 6 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Age 1-6 years inclusive at the time of screening
Residing in Bandiagara town
Appear to be in generally good health based on clinical and laboratory investigation
Separate written informed consent obtained from the parent/guardian before screening and study start, respectively
Available to participate in follow-up for the duration of study (26 months)

Who cannot join

Previous vaccination with an investigational vaccine or a rabies vaccine
Use of an 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
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first immunization. This exclusion includes any dose level of oral steroids or inhaled steroids, but not topical steroids.
Confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
Confirmed or suspected autoimmune disease
History of allergic reactions or anaphylaxis to immunizations or to any vaccine component

Show all 18Show fewer

History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care
History of allergy to tetracycline, doxycycline, nickel, Imidazole, eggs, neomycin, chlortetracycline or amphotericin B
History of splenectomy
Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than the upper limit of normal of the testing laboratory = 49.6 U/L)
Laboratory evidence of renal disease (serum or plasma creatinine greater than 62 micro mol/L), or more than trace protein or blood on urine dipstick testing)
Laboratory evidence of hematologic disease (absolute leukocyte count <5,300/mm^3 or >15,300/mm^3, absolute lymphocyte count <2,300 mm^3, platelet count <133,000/mm^3, or hemoglobin <9.0 g/dL)
Hepatitis B surface antigen positive
Chronic skin condition that could interfere with vaccine site reactogenicity assessment
Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period
Simultaneous participation in any other interventional clinical trial
Acute or chronic pulmonary, cardiovascular, hepatic (including hepatomegaly), renal or neurological condition, severe malnutrition, or any other clinical findings that in the opinion of the PI may increase the risk of participating in the study
Other condition that in the opinion of the Principal Investigator (PI) would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Trial locations and contacts

1 site in 1 country.

Mali1 site

University of Bamako, Malaria Research and Training Center
Bamako

Other trials in Mali

About this study

Official title: Randomized, Controlled Phase II Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the AMA-1 Malaria Vaccine FMP2.1/AS02A Versus Rabies Vaccine in 1-6 Year Old Children in Bandiagara, Mali

Malaria is a disease that affects many people in Africa. Malaria is caused by germs spread by mosquito bites. The purpose of this study is to compare the number of children who get malaria after receiving an experimental malaria vaccine (FMP2.1/AS02A) to the number of children who get malaria after receiving a vaccine for rabies (an approved vaccine that does not prevent malaria). The children will be assigned to one of the vaccine groups by chance. Participants and doctors will not know which vaccine was given. Study participants will include 400 children, ages 1-6 years, living in Bandiagara, Mali. Children will receive 3 vaccine doses, by injection, to their upper arm. Study procedures will include physical exams and several blood samples. Participants will be involved in the study for 26 months.

Read the detailed description

This is a randomized, controlled, phase II clinical trial to evaluate the efficacy, safety and immunogenicity of the apical membrane antigen-1 of Plasmodium (P.) falciparum (AMA-1) malaria vaccine FMP2.1/AS02A using rabies vaccine as a control in healthy children 1-6 years old in Bandiagara, Mali. This study is linked to DMID protocol 05-0146, which is a phase I dose escalation trial at the same site in the same population. In this study, 400 subjects will be randomized in a 1:1 ratio to receive either 50 micrograms of FMP2.1 in 0.5 mL AS02A or rabies vaccine. Immunizations will be given on days 0, 30 and 60. Solicited adverse events will be recorded on the days of immunization and at 1, 2, 3 and 7 days after each immunization. Unsolicited adverse events will be recorded for 30 days after each immunization. Passive case detection will be used to capture clinical malaria episodes and adverse events including serious adverse events, and will occur by continuous availability of clinical care in a population with high utilization of this care. Active surveillance will be used to capture malaria infections and adverse events including serious adverse events. For active case detection, following the third dose, participants will be followed monthly for 6 months and then at 12, 18 and 24 months after randomization, for clinical assessment, malaria smear and hemoglobin. Routine monthly malaria smears will not be read immediately unless symptoms are present. Children will be followed for 2 years after the first immunization. Sera will be collected for anti-FMP2.1 antibody titers on the days of immunization and 1, 3, 6, 8, 12, 18 and 24 months after the first immunization. Peripheral blood mononuclear cells (PBMCs) will be collected on the days of immunization, 30 days after the third immunization and 8, 12, 18 and 24 months after the first immunization. The study Final Report will be based on data collected up to 6 months after the assigned date of the third immunization. A supplemental report will include data from the entire 24-month observation period. Primary study objectives are to: determine the efficacy of FMP2.1/AS02A in children aged 1-6 years against first clinical malaria episodes (axillary temperature of greater than or equal to 37.5 degrees Celsius and parasitemia of greater than or equal to 2500/mm^3) occurring between randomization and 6 months after the assigned date of the third immunization; and assess the safety of the vaccine in children aged 1-6 years. Secondary study objectives are to: describe the dynamics of anti-AMA-1 antibody responses in recipients of the malaria vaccine compared to natural responses in the control group; determine whether serum anti-AMA-1 IgG titer by enzyme linked immunosorbent assay (ELISA) 1 month after the third immunization correlates with protection against clinical malaria episode; measure allele-specific efficacy against parasites with AMA-1 genotypes homologous to and heterologous to the 3D7 clone of P. falciparum; determine vaccine efficacy against clinical malaria episodes occurring between randomization and 6 months after the assigned date of the third immunization; and if efficacy is observed based on the primary endpoint, to determine vaccine efficacy against first clinical malaria episode and all clinical episodes (using increasing parasitemia thresholds) occurring during 2 years after randomization.

Conditions: Plasmodium Falciparum Malaria
Being tested: FMP2.1/AS02A, Rabies Vaccine
Keywords: malaria, Mali, children, Plasmodium falciparum, vaccine
Medical subject headings: Malaria, Falciparum, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FMP2.1/AS02ABiological
3 doses administered a month apart: 50 µg recombinant subunit protein FMP2.1 (Plasmodium falciparum Apical Membrane Antigen-1 from strain 3D7 expressed in and purified from Escherichia coli), adjuvanted with 0.5 mL of AS02A (proprietary oil-in-water emulsion and phosphate buffered saline with the immunostimulants monophosphoral lipid A and QS21).
Rabies VaccineBiological
White, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.

Study groups in NCT00460525
Study group	Role	What they receive
Rabies Vaccine	Active comparator	Rabies vaccine administered on Days 0, 30, and 60. Receives: Biological: Rabies Vaccine
FMP2.1/AS02A	Experimental	50 mcg of FMP2.1 in 0.5 mL AS02A administered on Days 0, 30, and 60. Receives: Biological: FMP2.1/AS02A

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the First Vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after each vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
Measured: 0-7 days after first vaccination
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Second Vaccination.
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
Measured: 0-7 days after the second vaccination
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Third Vaccination.
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
Measured: 0-7 days after the third vaccination
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the First Vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Measured: Day 0-29 after first vaccination
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the Second Vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Measured: Day 0-29 after second vaccination
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the Third Vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Measured: Day 0-29 after third vaccination
Time to First Clinical Malaria Episode With Significant Parasitemia (2500/mm^3) and Temperature of Greater Than or Equal to 37.5 Degrees C.
Time to first clinical malaria episode is displayed in a life table format to display the number of subjects at risk, the number with first clinical episode and the number censored at each time point.
Measured: Occurring between randomization and 6 months after the assigned date of the 3rd immunization.
Number of Subjects Reporting Serious Adverse Events
A serious adverse event was defined as any untoward medical occurrence that results in death, is life threatening, results in persistent or significant disability/incapacity, requires in-patient hospitalization or prolongation of existing hospitalization or is a congenital anomaly/birth defect in the offspring of a study subject. In addition, important medical events that may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above was considered serious.
Measured: 24 months after initial vaccination

Secondary outcomes (10)

Incidence Density of Clinical Malaria Episode
Clinical malaria episode was defined by significant parasitemia (2500/mm^3) and temperature of greater than or equal to 37.5 degrees C. Event rate was determined by dividing the number of episodes (150 for the Rabies group and 121 for the FMP2.1/ASO2A group) by the number of Person Years at Risk (PYAR) (126.341 for Rabies group and 127.411 for the FMP2.1/ASO2A group).
Measured: Between randomization and 6 months after 3rd immunization.
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by Enzyme Linked ImmunoSorbent Assay (ELISA) at Day 0
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 0 prior to the first vaccination.
Measured: Day 0
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 30.
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 30, prior to the second vaccination.
Measured: Day 30 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 60.
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 60, prior to the third vaccination.
Measured: Day 60 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 90.
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 90.
Measured: Day 90 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 150.
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 150.
Measured: Day 150 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 240.
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 240.
Measured: Day 240 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 364
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 364.
Measured: Day 364 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 547
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 547.
Measured: Day 547 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 730
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 730.
Measured: Day 730 after initial vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Jul 2009

First posted16 Apr 2007 (estimated)
Study startMay 2007
Primary completionJul 2009
Study completionJul 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 400 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00460525
Sponsor's protocol ID: 07-0003
Other IDs: U01AI065683, 2U01AI065683-06, Malaria-056 (110060), HSRRB # A-14262
Status last verified: Oct 2018
First submitted: 12 Apr 2007
Last updated: 9 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG, Haynes JD, Lanar DE. Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun. 2002 Jun;70(6):3101-10. doi: 10.1128/IAI.70.6.3101-3110.2002.
PubMed 12011004
Polhemus ME, Magill AJ, Cummings JF, Kester KE, Ockenhouse CF, Lanar DE, Dutta S, Barbosa A, Soisson L, Diggs CL, Robinson SA, Haynes JD, Stewart VA, Ware LA, Brando C, Krzych U, Bowden RA, Cohen JD, Dubois MC, Ofori-Anyinam O, De-Kock E, Ballou WR, Heppner DG Jr. Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naive adults at the Walter Reed Army Institute of Research. Vaccine. 2007 May 22;25(21):4203-12. doi: 10.1016/j.vaccine.2007.03.012. Epub 2007 Mar 26.
PubMed 17442466
Laurens MB, Kouriba B, Bergmann-Leitner E, Angov E, Coulibaly D, Diarra I, Daou M, Niangaly A, Blackwelder WC, Wu Y, Cohen J, Ballou WR, Vekemans J, Lanar DE, Dutta S, Diggs C, Soisson L, Heppner DG, Doumbo OK, Plowe CV, Thera MA. Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine. PLoS One. 2017 Mar 10;12(3):e0173294. doi: 10.1371/journal.pone.0173294. eCollection 2017.
PubMed 28282396
Graves SF, Kouriba B, Diarra I, Daou M, Niangaly A, Coulibaly D, Keita Y, Laurens MB, Berry AA, Vekemans J, Ripley Ballou W, Lanar DE, Dutta S, Gray Heppner D, Soisson L, Diggs CL, Thera MA, Doumbo OK, Plowe CV, Sztein MB, Lyke KE. Strain-specific Plasmodium falciparum multifunctional CD4(+) T cell cytokine expression in Malian children immunized with the FMP2.1/AS02A vaccine candidate. Vaccine. 2016 May 17;34(23):2546-55. doi: 10.1016/j.vaccine.2016.04.019. Epub 2016 Apr 15.
PubMed 27087149
Laurens MB, Thera MA, Coulibaly D, Ouattara A, Kone AK, Guindo AB, Traore K, Traore I, Kouriba B, Diallo DA, Diarra I, Daou M, Dolo A, Tolo Y, Sissoko MS, Niangaly A, Sissoko M, Takala-Harrison S, Lyke KE, Wu Y, Blackwelder WC, Godeaux O, Vekemans J, Dubois MC, Ballou WR, Cohen J, Dube T, Soisson L, Diggs CL, House B, Bennett JW, Lanar DE, Dutta S, Heppner DG, Plowe CV, Doumbo OK. Extended safety, immunogenicity and efficacy of a blood-stage malaria vaccine in malian children: 24-month follow-up of a randomized, double-blinded phase 2 trial. PLoS One. 2013 Nov 18;8(11):e79323. doi: 10.1371/journal.pone.0079323. eCollection 2013.
PubMed 24260195
Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Ouattara A, Kone AK, Guindo AB, Traore K, Traore I, Kouriba B, Diallo DA, Diarra I, Daou M, Dolo A, Tolo Y, Sissoko MS, Niangaly A, Sissoko M, Takala-Harrison S, Lyke KE, Wu Y, Blackwelder WC, Godeaux O, Vekemans J, Dubois MC, Ballou WR, Cohen J, Thompson D, Dube T, Soisson L, Diggs CL, House B, Lanar DE, Dutta S, Heppner DG Jr, Plowe CV. A field trial to assess a blood-stage malaria vaccine. N Engl J Med. 2011 Sep 15;365(11):1004-13. doi: 10.1056/NEJMoa1008115.
PubMed 21916638

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Controlled Phase II Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the AMA-1 Malaria Vaccine FMP2.1/AS02A Versus Rabies Vaccine in 1-6 Year Old Children in Bandiagara, Mali
ClinicalTrials.gov ID: NCT00460525
Acronym / sponsor ID: 07-0003
Conditions: Plasmodium Falciparum Malaria
Keywords: malaria, Mali, children, Plasmodium falciparum, vaccine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 400 participants (actual)
Lead sponsor: U.S. Army Medical Research and Development CommandUS federal agency
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline, University of Maryland
Study start: May 2007
Primary completion: Jul 2009 (actual)
Study completion: Jul 2009 (actual)
First posted: 16 Apr 2007 (estimated)
Results: Posted 10 Aug 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Rabies Vaccine	Active comparator	Biological: Rabies VaccineRabies vaccine administered on Days 0, 30, and 60.
FMP2.1/AS02A	Experimental	Biological: FMP2.1/AS02A50 mcg of FMP2.1 in 0.5 mL AS02A administered on Days 0, 30, and 60.

Who may qualify

Ages: 1 year to 6 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (5 listed)

Age 1-6 years inclusive at the time of screening
Residing in Bandiagara town
Appear to be in generally good health based on clinical and laboratory investigation
Separate written informed consent obtained from the parent/guardian before screening and study start, respectively
Available to participate in follow-up for the duration of study (26 months)

Key exclusion criteria (18 listed)

Previous vaccination with an investigational vaccine or a rabies vaccine
Use of an 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
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first immunization. This exclusion includes any dose level of oral steroids or inhaled steroids, but not topical steroids.
Confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
Confirmed or suspected autoimmune disease

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FMP2.1/AS02A3 doses administered a month apart: 50 µg recombinant subunit protein FMP2.1 (Plasmodium falciparum Apical Membrane Antigen-1 from strain 3D7 expressed in and purified from Escherichia coli), adjuvanted with 0.5 mL of AS02A (proprietary oil-in-water emulsion and phosphate buffered saline with the immunostimulants monophosphoral lipid A and QS21).	Biological	FMP2.1/AS02A
Rabies VaccineWhite, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.	Biological	Rabies Vaccine

Primary outcome

Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the First Vaccination
Time frame: 0-7 days after first vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after each vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Second Vaccination.
Time frame: 0-7 days after the second vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Third Vaccination.
Time frame: 0-7 days after the third vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the First Vaccination
Time frame: Day 0-29 after first vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the Second Vaccination
Time frame: Day 0-29 after second vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the Third Vaccination
Time frame: Day 0-29 after third vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Time to First Clinical Malaria Episode With Significant Parasitemia (2500/mm^3) and Temperature of Greater Than or Equal to 37.5 Degrees C.
Time frame: Occurring between randomization and 6 months after the assigned date of the 3rd immunization.
Time to first clinical malaria episode is displayed in a life table format to display the number of subjects at risk, the number with first clinical episode and the number censored at each time point.
Number of Subjects Reporting Serious Adverse Events
Time frame: 24 months after initial vaccination
A serious adverse event was defined as any untoward medical occurrence that results in death, is life threatening, results in persistent or significant disability/incapacity, requires in-patient hospitalization or prolongation of existing hospitalization or is a congenital anomaly/birth defect in the offspring of a study subject. In addition, important medical events that may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above was considered serious.

10 secondary outcomes

Incidence Density of Clinical Malaria Episode
Time frame: Between randomization and 6 months after 3rd immunization.
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by Enzyme Linked ImmunoSorbent Assay (ELISA) at Day 0
Time frame: Day 0
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 30.
Time frame: Day 30 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 60.
Time frame: Day 60 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 90.
Time frame: Day 90 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 150.
Time frame: Day 150 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 240.
Time frame: Day 240 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 364
Time frame: Day 364 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 547
Time frame: Day 547 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 730
Time frame: Day 730 after initial vaccination

Results and safety

Results posted to the registry on 10 Aug 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rabies Vaccine	201	190
FMP2.1/AS02A	199	194

Primary outcome: Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the First Vaccination

Time frame: 0-7 days after first vaccination. Number. Unit: Participants

Measure	Rabies Vaccine n = 201	FMP2.1/AS02A n = 199
Drowsiness	0	5
Irritability/Fussiness	0	12
Loss of Appetite	3	25
Vomiting	1	4
Fever	30	61
Site Pain	55	157
Swelling	34	153
Erythema	0	12

Population analysed: All subjects receiving the vaccination are included.

Primary outcome: Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Second Vaccination.

Time frame: 0-7 days after the second vaccination. Number. Unit: Participants

Measure	Rabies Vaccine n = 193	FMP2.1/AS02A n = 193
Drowsiness	0	0
Irritability/Fussiness	1	5
Loss of Appetite	1	10
Vomiting	3	3
Fever	13	64
Site Pain	57	132
Swelling	69	151
Erythema	0	1

Population analysed: All subjects receiving the vaccination are included.

Primary outcome: Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Third Vaccination.

Time frame: 0-7 days after the third vaccination. Number. Unit: Participants

Measure	Rabies Vaccine n = 187	FMP2.1/AS02A n = 184
Drowsiness	1	0
Irritability/Fussiness	2	6
Loss of Appetite Post	0	3
Vomiting	2	2
Fever	18	64
Site Pain	48	134
Swelling	90	159
Erythema	0	3

Population analysed: All subjects receiving the vaccination are included.

Primary outcome: Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the First Vaccination

Time frame: Day 0-29 after first vaccination. Number. Unit: Adverse Events

Measure	Rabies Vaccine n = 201	FMP2.1/AS02A n = 199
Blood and lymphatic system disorders	7	4
Ear and labyrinth disorders	0	0
Eye disorders	5	5
Gastrointestinal disorders	17	11
General disorders, administrative site conditions	16	44
Hepatobiliary disorders	2	0
Infections and infestations	56	53
Injury, poisoning, and procedural complications	5	4

Population analysed: All subjects receiving the vaccination are included.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited adverse events were collected for 7 days after each immunization. Serious adverse events and unsolicited non-serious adverse events were collected for 24 months after initial vaccination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rabies Vaccine	2 of 201 (1%)	198 of 201 (98.5%)	Not reported
FMP2.1/AS02A	8 of 199 (4%)	199 of 199 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 12011004Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG, Haynes JD, Lanar DE. Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun. 2002 Jun;70(6):3101-10. doi: 10.1128/IAI.70.6.3101-3110.2002.
Results publication: PubMed 17442466Polhemus ME, Magill AJ, Cummings JF, Kester KE, Ockenhouse CF, Lanar DE, Dutta S, Barbosa A, Soisson L, Diggs CL, Robinson SA, Haynes JD, Stewart VA, Ware LA, Brando C, Krzych U, Bowden RA, Cohen JD, Dubois MC, Ofori-Anyinam O, De-Kock E, Ballou WR, Heppner DG Jr. Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naive adults at the Walter Reed Army Institute of Research. Vaccine. 2007 May 22;25(21):4203-12. doi: 10.1016/j.vaccine.2007.03.012. Epub 2007 Mar 26.
Derived from this study: PubMed 28282396Laurens MB, Kouriba B, Bergmann-Leitner E, Angov E, Coulibaly D, Diarra I, Daou M, Niangaly A, Blackwelder WC, Wu Y, Cohen J, Ballou WR, Vekemans J, Lanar DE, Dutta S, Diggs C, Soisson L, Heppner DG, Doumbo OK, Plowe CV, Thera MA. Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine. PLoS One. 2017 Mar 10;12(3):e0173294. doi: 10.1371/journal.pone.0173294. eCollection 2017.
Derived from this study: PubMed 27087149Graves SF, Kouriba B, Diarra I, Daou M, Niangaly A, Coulibaly D, Keita Y, Laurens MB, Berry AA, Vekemans J, Ripley Ballou W, Lanar DE, Dutta S, Gray Heppner D, Soisson L, Diggs CL, Thera MA, Doumbo OK, Plowe CV, Sztein MB, Lyke KE. Strain-specific Plasmodium falciparum multifunctional CD4(+) T cell cytokine expression in Malian children immunized with the FMP2.1/AS02A vaccine candidate. Vaccine. 2016 May 17;34(23):2546-55. doi: 10.1016/j.vaccine.2016.04.019. Epub 2016 Apr 15.
Derived from this study: PubMed 24260195Laurens MB, Thera MA, Coulibaly D, Ouattara A, Kone AK, Guindo AB, Traore K, Traore I, Kouriba B, Diallo DA, Diarra I, Daou M, Dolo A, Tolo Y, Sissoko MS, Niangaly A, Sissoko M, Takala-Harrison S, Lyke KE, Wu Y, Blackwelder WC, Godeaux O, Vekemans J, Dubois MC, Ballou WR, Cohen J, Dube T, Soisson L, Diggs CL, House B, Bennett JW, Lanar DE, Dutta S, Heppner DG, Plowe CV, Doumbo OK. Extended safety, immunogenicity and efficacy of a blood-stage malaria vaccine in malian children: 24-month follow-up of a randomized, double-blinded phase 2 trial. PLoS One. 2013 Nov 18;8(11):e79323. doi: 10.1371/journal.pone.0079323. eCollection 2013.
Derived from this study: PubMed 21916638Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Ouattara A, Kone AK, Guindo AB, Traore K, Traore I, Kouriba B, Diallo DA, Diarra I, Daou M, Dolo A, Tolo Y, Sissoko MS, Niangaly A, Sissoko M, Takala-Harrison S, Lyke KE, Wu Y, Blackwelder WC, Godeaux O, Vekemans J, Dubois MC, Ballou WR, Cohen J, Thompson D, Dube T, Soisson L, Diggs CL, House B, Lanar DE, Dutta S, Heppner DG Jr, Plowe CV. A field trial to assess a blood-stage malaria vaccine. N Engl J Med. 2011 Sep 15;365(11):1004-13. doi: 10.1056/NEJMoa1008115.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mahamadou A Thera, MD, MPH principal investigator

University of Bamako

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FMP2.1/AS02A and Rabies Vaccine in people with Plasmodium Falciparum Malaria, run by U.S. Army Medical Research and Development Command at 1 site in Mali.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the First Vaccination (time frame: 0-7 days after first vaccination). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00460525, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2018.