Safety and Immunogenicity of Pfs25M-EPA/AS01 and Pfs230D1M-EPA/AS01 Vaccines, Transmission Blocking Vaccines Against Plasmodium Falciparum, at Full and Fractional Dosing in Adults in Mali

NCT02942277 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 99991700617-I-N006
• Study Type: interventional
• Target: 301
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Researchers are looking for new ways to control and eradicate malaria. They want to test vaccines to block malaria transmission in adults in Mali. These vaccines work by inducing antibodies in a person. The antibody is then taken up with blood by a mosquito that bites the person. This blocks parasite development in the mosquito. This stops malaria transmission to another person. Objective: To test the safety, reactogenicity, immunogenicity, and transmission-blocking activity of the vaccines Pfs25M-EPA and Pfs230D1M-EPA with AS01 in Malian adults. Eligibility: Healthy Malians ages 18-50 living in certain areas in Mali who: Are not pregnant or breastfeeding Are not infected with HIV, Hepatitis B and Hepatitis C Do not have evidence of immunodeficiency Do not have history of severe allergic reaction or anaphylaxis Design: Participants will be screened with: Medical history Physical exam Malaria Comprehension Exam Blood and urine tests Electrocardiogram (for participants in certain study groups) Participants will be randomly assigned to a study group. Participants will be monitored for 12-16 months. For the first 7 months, they will have between 1 and nine visits a month. The number depends on the month and on what group they are in. For the rest of the months, they will have 1 monthly visit. Each visit includes a physical exam. Most include blood tests. Participants will get 3 doses of a study or comparator vaccine. They get the vaccine through an injection in the upper arm. This occurs at their first visit, then 1 month later, and then 5 months later. Participants will be followed for at least 6 months after the last vaccine. If participants develop an injection site rash or reaction, photographs may be taken of the site.

Conditions

Malaria

Keywords

Malaria; Reactogenicity; Antibody; Direct Skin Feed; Mosquito

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Local and Systemic Adverse Events in Year 1

  Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine

  Within 7 days after each vaccination

• Number of Participants With Local and Systemic Adverse Events in Year 2

  Number of participants with local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine

  Within 7 days after each vaccination

Study Arms (11)

1a

EXPERIMENTAL

(n=5), to receive 16 microgram Pfs25M-EPA/AS01 on D0, D28, D168

Biological: Pfs25M-EPA; Other: AS01; Other: Normal Saline

1b

EXPERIMENTAL

(n=10), to receive 47 microgram Pfs25M-EPA/AS01 on D0, D28, D168

Biological: Pfs25M-EPA; Other: AS01

2a

EXPERIMENTAL

(n=5), to receive 13 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168

Biological: Pfs230D1M-EPA; Other: AS01; Other: Normal Saline

2b

EXPERIMENTAL

(n=10), to receive 40 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168

Biological: Pfs230D1M-EPA; Other: AS01

2c

EXPERIMENTAL

(n=60), to receive 40 micrograms Pfs230D1M-EPA/AS01 on D0, D28, D168; all subjects will undergo antimalarial drug treatment with Coartem on D-7 (prior to vaccination #1); 4th vaccination on D476

Biological: Pfs230D1M-EPA; Other: AS01; Drug: Coartem

2d

EXPERIMENTAL

(n=60), to receive 40 micrograms Pfs230D1M-EPA/AS01 (500 (Micro)L TBV + AS01) on D0, D28, then 8 micro liters Pfs230D1M- EPA/AS01 (100 (Micro)L TBV + AS01;fractional dose) on D168; all subjects will undergo antimalarial drug treatment with Coartem on D-7 (prior to vaccination #1); 4th vaccination on D476

Biological: Pfs230D1M-EPA; Other: AS01; Drug: Coartem

3a

EXPERIMENTAL

(n=5), to receive 16 microgram Pfs25M-EPA/AS01 and 13 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168

Biological: Pfs25M-EPA; Biological: Pfs230D1M-EPA; Other: AS01; Other: Normal Saline

3b

EXPERIMENTAL

(n=10), to receive 47 microgram Pfs25M-EPA/AS01 and 40 microgram Pfs230D1M-EPA/AS01 on D0, D28, D168 (Bamako)

Biological: Pfs25M-EPA; Biological: Pfs230D1M-EPA; Other: AS01

4a

ACTIVE COMPARATOR

(n=10), to receive ENGERIX-B on D0, D28, and D168

Biological: Engerix-B; Other: Normal Saline

4b

ACTIVE COMPARATOR

(n=10), to receive ENGERIX-B on DO, D28, and Dl68

Biological: Engerix-B; Drug: Coartem

4c

ACTIVE COMPARATOR

(n=120), to receive ENGERIX-B on D0, D28, and D168 (start study with Arm 2c and 2d); all subjects will undergo antimalarial drug treatment with Coartem on D-7 (prior to vaccination #1); vaccination with Menactra on D476

Biological: Engerix-B; Biological: Menactra; Drug: Coartem

Interventions

Pfs25M-EPA BIOLOGICAL

The PpPfs25M and EcEPA lots, both manufactured at Walter Reed Bioproduction facility (Silver Spring, Maryland) in cGMP compliance, were used to manufacture the conjugate. PpPfs25M is a Pichia- expressed recombinant Pfs25 with a molecular mass of 18,713 Daltons.The Pfs25M- EPA was formulated as conjugated Pfs25M in 4 mM PBS to a 2X dilution of the high dose (188 (Micro)g/ml in 0.5 ml volume) in cGMP compliance at Walter Reed Bio-production facility in April 2016 and will be provided as a single use vial.

1a; 1b; 3a; 3b

Pfs230D1M-EPA BIOLOGICAL

The Pfs230D1M-EPA was formulated as conjugated Pfs230D1M in 4 mM PBS to a 2X dilution of the high dose (160 (Micro)g/ml in 0.5 ml volume) in cGMP compliance at Walter Reed Bio-production facility in April 2016 and will be provided as a single use vial.

2a; 2b; 2c; 2d; 3a; 3b

AS01 OTHER

AS01B adjuvant will also be provided as a single use vial by GSK, 100 microgram/mL MPL and 100microgram/mL QS21 in a liposomal formulation in a volume of 0.625 mL. One dose injected of AS01B corresponds to 50 μg QS21 and 50 μg MPL.

1a; 1b; 2a; 2b; 2c; 2d; 3a; 3b

Engerix-B BIOLOGICAL

ENGERIX-B (hepatitis B vaccine; recombinant): is a sterile suspension of noninfectious hepatitis B virus surface antigen (HBsAg) for intramuscular administration. It contains purified HBsAg obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus. Each 1-mL adult dose contains 20 g of HBsAg adsorbed on 0.5 mg aluminum as aluminum hydroxide. FDA approved for persons 20 years of age and older for a series of 3 doses on a 0-, 1-, 6-month schedule.

4a; 4b; 4c

Menactra BIOLOGICAL

Menactra is FDA approved for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 (but does not protect against serotype B) for use in individuals 9 months through 55 years of age

4c

Normal Saline OTHER

Sterile isotonic (0.9%) normal saline will be commercially procured in the US and shipped to Mali at ambient temperature. Normal saline will be administered in a 0.5 mL dose as an intramuscular injection. Normal saline will also be used for diluting Pfs25M-EPA and Pfs230D1M-EPA prior to formulation with AS01B for the lower dose groups in Bamako, Mali.

1a; 2a; 3a; 4a

Coartem DRUG

Artemether/lumefantrine (Coartem(R)) is a licensed antimalarial in the US and Mali for treatment of uncomplicated malaria. It has an excellent safety profile and is widely used to treat malaria. Subjects who may have any contraindications to the use of these drugs will be excluded at screening. Coartem will be dosed with food and administered over 3 days for a total of 6 doses, as per package insert and standard adult dosing

2c; 2d; 4b; 4c

Eligibility Criteria

• Age: 18 Years - 52 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age greater than or equal to 18 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 in the opinion of the investigator.
• Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to Study Day 0 (Study Day 476 for re-enrollment) and then until 3 months after 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.
• 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 DSFs (Arms 3c, 3d, 4c only).
• Known resident of Bancoumana or Doneguebougou or surrounding area or known student or long term resident (more than 1 year) of Bamako/Sotuba, Mali

You may not qualify if:

• Pregnancy as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test (if female).
• NOTE: Pregnancy is also a criteria for discontinuation of any further dosing or non-safety 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 laboratory-defined limits of normal (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range and less than or equal to Grade 1).
• 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 and less than or equal to Grade 1).
• 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.
• Severe asthma, defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years.
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sj(SqrRoot)(Delta)gren s syndrome, or autoimmune thrombocytopenia.
• Known immunodeficiency syndrome.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Bancoumana Malaria Vaccine Center

Bamako, Mali

Location

Related Publications (5)

• Wu Y, Przysiecki C, Flanagan E, Bello-Irizarry SN, Ionescu R, Muratova O, Dobrescu G, Lambert L, Keister D, Rippeon Y, Long CA, Shi L, Caulfield M, Shaw A, Saul A, Shiver J, Miller LH. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18243-8. doi: 10.1073/pnas.0608545103. Epub 2006 Nov 16.

  PMID: 17110440 BACKGROUND

• Tachibana M, Wu Y, Iriko H, Muratova O, MacDonald NJ, Sattabongkot J, Takeo S, Otsuki H, Torii M, Tsuboi T. N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity. Clin Vaccine Immunol. 2011 Aug;18(8):1343-50. doi: 10.1128/CVI.05104-11. Epub 2011 Jun 29.

  PMID: 21715579 BACKGROUND

• Diallo M, Toure AM, Traore SF, Niare O, Kassambara L, Konare A, Coulibaly M, Bagayogo M, Beier JC, Sakai RK, Toure YT, Doumbo OK. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar J. 2008 Dec 2;7:248. doi: 10.1186/1475-2875-7-248.

  PMID: 19055715 BACKGROUND

• Healy SA, Sagara I, Assadou MH, Katile A, Kone M, Imeru A, Kwan JL, Swihart BJ, Fintzi J, Potter GE, Zeguime A, Dolo A, Diarra B, Narum DL, Rausch KM, MacDonald NJ, Zhu D, Mohan R, Thera I, Morrison RD, Zaidi I, Doritchamou JYA, Sylla D, Hume JCC, Coulibaly MB, Morelle D, Lievens M, Doumbo OK, Duffy PE; Pfs230D1 Vaccine Team. A Vaccine to Block Plasmodium falciparum Transmission. NEJM Evid. 2025 Jul;4(7):EVIDoa2400188. doi: 10.1056/EVIDoa2400188. Epub 2025 Jun 24.

  PMID: 40552966 DERIVED

• 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

MeSH Terms

Conditions

Malaria

Interventions

Engerix-B; Meningococcal Vaccines; Saline Solution; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations

Limitations and Caveats

No limitations or caveats to report.

Results Point of Contact

• Title: Patrick E. Duffy
• Organization: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

patrick.duffy@nih.gov

301.761.5089

Study Officials

• Patrick E Duffy, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

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: October 21, 2016
• First Posted: October 24, 2016
• Study Start: October 21, 2016
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: December 10, 2024
• Results First Posted: January 28, 2022

Record last verified: 2020-07-29

Locations

MA (1)