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

NCT00460525 | Completed Phase 2 Results DMC

• 5 other identifiers: 07-0003U01AI0656832U01AI065683-06Malaria-056 (110060)HSRRB # A-14262
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Plasmodium Falciparum Malaria

Keywords

malaria, Mali, children, Plasmodium falciparum, vaccine

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  24 months after initial vaccination

Secondary Outcomes (10)

• Incidence Density of Clinical Malaria Episode

  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

  Day 0

• Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 30.

  Day 30 after initial vaccination

• Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 60.

  Day 60 after initial vaccination

• Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 90.

  Day 90 after initial vaccination

Study Arms (2)

Rabies Vaccine

ACTIVE COMPARATOR

Rabies vaccine administered on Days 0, 30, and 60.

Biological: Rabies Vaccine

FMP2.1/AS02A

EXPERIMENTAL

50 mcg of FMP2.1 in 0.5 mL AS02A administered on Days 0, 30, and 60.

Biological: FMP2.1/AS02A

Interventions

FMP2.1/AS02A BIOLOGICAL

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).

FMP2.1/AS02A

Rabies Vaccine BIOLOGICAL

White, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.

Rabies Vaccine

Eligibility Criteria

• Age: 1 Year - 6 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• GlaxoSmithKline: collaborator
• University of Maryland: collaborator

Study Sites (1)

University of Bamako, Malaria Research and Training Center

Bamako, Mali

Location

Related Publications (6)

• 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.

  PMID: 12011004 RESULT

• 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.

  PMID: 17442466 RESULT

• 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.

  PMID: 28282396 DERIVED

• 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.

  PMID: 27087149 DERIVED

• 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.

  PMID: 24260195 DERIVED

• 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.

  PMID: 21916638 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Mahamadou A. Thera, MD, MPH
• Organization: Department of Epidemiology of Parasitic Diseases, University of Bamako

mthera@mrtcbko.org

223-222-8109

Study Officials

• Mahamadou A Thera, MD, MPH

  University of Bamako

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2007
• First Posted: April 16, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: November 9, 2018
• Results First Posted: August 10, 2010

Record last verified: 2018-10

Locations

MA (1)