Study of the Safety and Immunogenicity of Pfs230D1M-EPA/Alhydrogel and Pfs25M-EPA/Alhydrogel , a Transmission Blocking Vaccine Against Plasmodium Falciparum Malaria, in Adults in the U.S. and Mali

NCT02334462 | Completed Phase 1 FDA Drug

• 2 other identifiers: 15004415-I-0044
• Study Type: interventional
• Target: 538
• Locations: 2 countries
• Sites: 2

Brief Summary

Background: \- Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito that carries the parasite bites them. Malaria infection does not happen in the United States, but many people in Africa, Asia, and South America are at risk for it. Researchers want to test two vaccines that may help decrease malaria infection. Objective: \- To see if two vaccines (Pfs25M-EPA/Alhydrogel and Pfs230DIM-EPA/Alhydrogel ) are safe in humans and cause an immune response that will prevent malaria parasites from correctly growing in the mosquito. Eligibility: \- Healthy adults ages 18 50. Design:

• There are several groups in this study. Each group will receive a different dose of the vaccine and some groups will received both vaccines.
• Vaccinations will be given on two days about 4 weeks apart.
• Participants will receive each vaccine as an injection into the arm. Blood will be drawn on the day of vaccination.
• In the 4 weeks after receiving a vaccination, participants will have at least 3 clinic visits and 1 phone contact. They will have at least 3 more visits and 3 phone contacts over the next 6 months.
• At each visit, participants will be evaluated for side effects to the vaccine and any new health changes or problems. They will be asked how they are feeling and if they have taken any medicine. Blood and urine samples may be taken at the visit. More follow-up visits may be needed to follow up on changes or problems.

Conditions

Malaria

Keywords

Assays; Antibody; Reactogenicity; Mosquito; Responses

Outcome Measures

Primary Outcomes (1)

• Incidence of local and systemic adverse events and serious advents in U.S. adults and in exposed Malian adults.

  U.S. Study: Days 1,3,7,14,28,29,31,35,42,56,84,112,140,168 and 196. Same as U.S. plus Days 169,171,175,182,189,196,203,210,217,240,2 70,300,330,360,390,420,450,480,510,540,541,543,547,554,561,568,575,582,589,610,640,670,700,730

Secondary Outcomes (1)

• Anti -Pfs25 and Anti-Pfs230 antibody levels elicited by as measured by ELISA in U.S. adults and in exposed Malian adults

  U.S. Study: D. 14,28,42,84,140,196 Mali (Safety Arm: Same as the U.S. Mali (Functional Arm): D. 14,28,42,84,140,168,182,196,210,240,300,360,420,480,540,554,568,582,610,670,730

Study Arms (7)

Group 1- Mali

EXPERIMENTAL

Arm A1 (N=5) to receive 16 micrograms Pfs25M on D0, D28 Arm A2 (N=50) to receive 47 micrograms Pfs25M and Normal Saline on D0, D28, D168, D530

Biological: Pfs25M-EPA/Alhydrogel

Group 1-U.S

EXPERIMENTAL

Arm 1a (N=5) to receive 16 micrograms Pfs25M on D0, D28. Arm 1b (N=5) to receive 47 micrograms Pfs25M on D0, D28.

Biological: Pfs25M-EPA/Alhydrogel

Group 2- Mali

EXPERIMENTAL

Arm B1 (N=5) to receive 15 micrograms Pfs230D1M on D0, D28 Pfs230D1M-EPA/Alhydrogel Arm B2 (N=50) to receive 40 micrograms Pfs230D1M and Normal Saline on D0, D28, D168, D530

Biological: Pfs230D1M-EPA/Alhydrogel

Group 2-U.S

EXPERIMENTAL

Arm 2a (N=5) to receive 5 micrograms Pfs230D1M on D0, D28.Arm 2b (N=5) to receive 15 micrograms Pgs230D1M on D0, D28. Arm 2c (N=5) to receive 40 micrograms Pfs230D1M on D0, D28.

Biological: Pfs230D1M-EPA/Alhydrogel

Group 3- Mali

EXPERIMENTAL

Arm C1 (N=5) to receive 16 micrograms Pfs25M and 15 micrograms Pfs230D1M on D0, D28Arm C2 (N=50) to receive 47 micrograms Pfs25M and 40 microgramsPfs230D1M on D0, D28, D168, D530

Biological: Pfs230D1M-EPA/Alhydrogel; Biological: Pfs25M-EPA/Alhydrogel

Group 3- U.S.

EXPERIMENTAL

Arm 3a (N=5) to receive 16 micrograms Pfs25M and 15 micrograms Pfs230D1M on D0, D28. Arm 3b (N=5) to receive 47 micrograms Pfs25M and 40 micrograms Pfs230D1M on D0, D28.

Biological: Pfs230D1M-EPA/Alhydrogel; Biological: Pfs25M-EPA/Alhydrogel

Group 4- Mali

ACTIVE COMPARATOR

Arm D1 (N=5) to receive TWINRIX on D0, D28Arm D2 (N=5) to receive TWINRIX and NormalSaline on D0, D28Arm D3 (N=50) to receive TWINRIX and NormalSaline on D0, D28, D168; to receive Menactra andNormal Saline on D530

Drug: TWINRIX; Drug: Menactra

Interventions

Pfs230D1M-EPA/Alhydrogel BIOLOGICAL

Group 2- Mali; Group 2-U.S; Group 3- Mali; Group 3- U.S.

Pfs25M-EPA/Alhydrogel BIOLOGICAL

Group 1- Mali; Group 1-U.S; Group 3- Mali; Group 3- U.S.

TWINRIX DRUG

Group 4- Mali

Menactra DRUG

Group 4- Mali

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• All of the following criteria must be fulfilled for a volunteer to participate in this trial:
• Age greater than or equal to18 and less than or equal to 50 years.
• Available for the duration of the trial.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• In good general health and without clinically significant medical history.
• Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to Study Day 0 to 3 months after the last vaccination.
• Reliable methods of birth control include one of the following: confirmed pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable device.
• Reliable methods of birth control include concurrent use of a pharmacologic and a barrier method, i.e. two of the following: confirmed pharmacologic contraceptives (oral, transdermal) delivery or vaginal ring AND condoms with spermicide or diaphragm with spermicide.
• Abstinence of potentially reproductive sexual activity.
• Non-childbearing women will also be required to report date of last menstrual period, history of surgical sterility (i.e. tubal ligation, hysterectomy) or premature ovarian insufficiency (POI), and will have a baseline urine or serum pregnancy test performed.
• Willingness to have blood samples stored for future research.
• Willingness to undergo direct skin feeds (Mali only).
• Known resident of Bancoumana or surrounding area (Mali only).

You may not qualify if:

• A subject will be excluded from participating in this trial if any one of the following criteria is
• fulfilled:
• Pregnancy as determined by a positive urine or serum human choriogonadotropin ( \<=- hCG) test (if female).
• NOTE: Pregnancy is also a criteria for discontinuation of any further dosing or nonsafety related interventions for that subject.
• Currently breast-feeding (if female).
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol.
• Hemoglobin, WBC, absolute neutrophils, and platelets outside the local laboratorydefined limits of normal (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range).
• Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range).
• Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or
• hepatitis B (HBV).
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
• History of receiving any investigational product within the past 30 days.
• Participation or planned participation in a clinical trial with an investigational product prior to completion of the follow up visit 28 days following last vaccination OR planned participation in an investigational vaccine study until the last required protocol visit
• Subject has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
• History of a severe allergic reaction or anaphylaxis.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Rodolphe Merieux Laboratory@@@Bamako, Mali: collaborator

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Malaria Research and Training Center

Bamako, Mali

Location

Related Publications (8)

• Farrance CE, Rhee A, Jones RM, Musiychuk K, Shamloul M, Sharma S, Mett V, Chichester JA, Streatfield SJ, Roeffen W, van de Vegte-Bolmer M, Sauerwein RW, Tsuboi T, Muratova OV, Wu Y, Yusibov V. A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum. Clin Vaccine Immunol. 2011 Aug;18(8):1351-7. doi: 10.1128/CVI.05105-11. Epub 2011 Jun 29.

  PMID: 21715576 BACKGROUND

• Kaslow DC, Quakyi IA, Syin C, Raum MG, Keister DB, Coligan JE, McCutchan TF, Miller LH. A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains. Nature. 1988 May 5;333(6168):74-6. doi: 10.1038/333074a0.

  PMID: 3283563 BACKGROUND

• Shimp RL Jr, Rowe C, Reiter K, Chen B, Nguyen V, Aebig J, Rausch KM, Kumar K, Wu Y, Jin AJ, Jones DS, Narum DL. Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle. Vaccine. 2013 Jun 19;31(28):2954-62. doi: 10.1016/j.vaccine.2013.04.034. Epub 2013 Apr 24.

  PMID: 23623858 BACKGROUND

• Cao Y, da Silva Araujo M, Lorang CG, Dos Santos NAC, Tripathi A, Vinetz J, Kumar N. Distinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1. Vaccine. 2025 Feb 15;47:126696. doi: 10.1016/j.vaccine.2024.126696. Epub 2025 Jan 8.

  PMID: 39787798 DERIVED

• Sagara I, Healy SA, Assadou MH, Kone M, Swihart BJ, Kwan JL, Fintzi J, Sissoko K, Kamate B, Samake Y, Guindo MA, Doucoure M, Niare K, Dolo A, Diarra B, Rausch KM, Narum DL, Jones DS, MacDonald NJ, Zhu D, Gorres JP, Imeru A, Mohan R, Thera I, Zaidi I, Salazar-Miralles F, Duan J, Neal J, Morrison RD, Muratova O, Sylla D, O'Connell EM, Wu Y, Hume JCC, Coulibaly MB, Anderson CF, Traore SF, Doumbo OK, Duffy PE. Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial. Lancet Infect Dis. 2023 Nov;23(11):1266-1279. doi: 10.1016/S1473-3099(23)00276-1. Epub 2023 Jul 24.

  PMID: 37499679 DERIVED

• Fantin RF, Coelho CH, Berhe AD, Magalhaes LMD, Pereira DB, Salinas ND, Tolia NH, Amaratunga C, Suon S, Sagara I, Narum DL, Fujiwara RT, Abejon C, Campos-Neto A, Duffy PE, Bueno LL. Immunological characterization of a VIR protein family member (VIR-14) in Plasmodium vivax-infected subjects from different epidemiological regions in Africa and South America. PLoS Negl Trop Dis. 2023 Apr 7;17(4):e0011229. doi: 10.1371/journal.pntd.0011229. eCollection 2023 Apr.

  PMID: 37027391 DERIVED

• Healy SA, Anderson C, Swihart BJ, Mwakingwe A, Gabriel EE, Decederfelt H, Hobbs CV, Rausch KM, Zhu D, Muratova O, Herrera R, Scaria PV, MacDonald NJ, Lambert LE, Zaidi I, Coelho CH, Renn JP, Wu Y, Narum DL, Duffy PE. Pfs230 yields higher malaria transmission-blocking vaccine activity than Pfs25 in humans but not mice. J Clin Invest. 2021 Apr 1;131(7):e146221. doi: 10.1172/JCI146221.

  PMID: 33561016 DERIVED

• Guindo A, Sagara I, Ouedraogo B, Sallah K, Assadou MH, Healy S, Duffy P, Doumbo OK, Dicko A, Giorgi R, Gaudart J. "Spatial heterogeneity of environmental risk in randomized prevention trials: consequences and modeling". BMC Med Res Methodol. 2019 Jul 15;19(1):149. doi: 10.1186/s12874-019-0759-z.

  PMID: 31307393 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

twinrix; Meningococcal Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Patrick E Duffy, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2015
• First Posted: January 8, 2015
• Study Start: January 7, 2015
• Primary Completion: March 31, 2016
• Study Completion: October 22, 2018
• Last Updated: April 11, 2019

Record last verified: 2018-10-22

Locations

MA (1); US (1)