Pfs230D1M-EPA/AS01 Vaccine, a Transmission Blocking Vaccine Against Plasmodium Falciparum, in an Age De-Escalation Trial of Children and a Family Compound Trial in Mali

NCT03917654 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 99991908619-I-N086
• Study Type: interventional
• Target: 1,301
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Malaria affects many people in Mali and other parts of Africa. It is spread by mosquito bites. Malaria can make people sick or can lead to death. Scientists want to learn if a vaccine can stop it from spreading to other people. Objective: To test how well an experimental malaria vaccine works to decrease malaria infections. Eligibility: Healthy people ages 5 and older who live in Doneguebougou, Mali, and surrounding areas Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests EKG Participants will be randomly assigned to get either the experimental vaccine or an approved vaccine. They will not know which they are getting. Participants will have a visit about a week before their first vaccine. They will take a medicine that kills malaria. They will take it at the clinic the next 2 days. Participants ages 5-8 will take the drug again 2 weeks before their third vaccine. Participants get the vaccine through a needle in the arm. They will have visits 1, 3, 7, and 14 days after. They will have blood tests or finger pricks. Participants will get another vaccine 1 and 6 months later. Participants will have blood tests once a month. At these visits they may also have urines tests or mosquito feeds. For the feeds a cup full of mosquitoes will be placed on arms or legs for 15-20 minutes. Participants will have visits twice a month for 4 months after their last vaccine.

Conditions

Malaria

Keywords

Randomized; Assays; Blood Smear; Antibody; Parasites

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Local and Systemic Adverse Events in Years 1 and 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 at days, 0, 28, 126, 448 (for arms 1a, 1b, 2a, 2b), days 0, 28, 56, 392 (for arms 3a, 3b, 3c, 3d, 3e, 3f), days -14 and 385 (for arms 4a, 4b) and year 2 (for all arms)

Study Arms (8)

Arm 1a/3c

EXPERIMENTAL

Arm 1a (pilot) + Arm 3c (main) to receive 40ug of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of artemether/lumefantrine (AL) on day -7

Biological: Pfs230D1M-EPA/AS01; Biological: AVAXIM

Arm 1b/3d

ACTIVE COMPARATOR

Arm 1b (pilot) + Arm 3d (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7

Biological: HAVRIX; Biological: Menactra

Arm 2a/3a

EXPERIMENTAL

Arm 2a (pilot) + Arm 3a (main) to receive 40ug of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of AL on day -7 and 154

Biological: Pfs230D1M-EPA/AS01

Arm 2b/3b

ACTIVE COMPARATOR

Arm 2b (pilot) + Arm 3b (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7 and 154

Biological: HAVRIX; Biological: Menactra

Arm 3e

EXPERIMENTAL

Arm 3e (main) to receive 40microg of Pfs230D1M-EPA/AS01 on days 0, 28, 168; receipt of AL on day -7

Biological: Pfs230D1M-EPA/AS01

Arm 3f

ACTIVE COMPARATOR

Arm 3f (main) to receive HAVRIX (day 0), TYPHIM Vi (day 28), HAVRIX (day 168); receipt of AL on day -7

Biological: HAVRIX; Biological: TYPHIM Vi (Salmonella typhi vaccine); Biological: Menactra

Arm 4a

NO INTERVENTION

Receipt of AL on day 154

Arm 4b

NO INTERVENTION

Receipt of AL on day 154

Interventions

Pfs230D1M-EPA/AS01 BIOLOGICAL

The Pfs230D1M-EPA was formulated as conjugated Pfs230D1M in 4 mM phosphate-buffered saline (PBS) to a 2X dilution of the high dose (160 (Micro)g/mL in 0.5 mL volume) in cGMP compliance at Walter Reed Bioproduction facility in April 2016 and will be provided as a single use vial. AS01B adjuvant was manufactured for use in the SHINGRIX vaccine by GSK

Arm 1a/3c; Arm 2a/3a; Arm 3e

HAVRIX BIOLOGICAL

HAVRIX (Hepatitis A Vaccine; HAV) is produced by GSK and is a sterile suspension of inactivated virus for IM administration. The virus (strain HM175) is propagated in MRC-5 human diploid cells. HAVRIX is FDA approved for active immunization against disease caused by HAV for persons 12 months of age and older.

Arm 1b/3d; Arm 2b/3b; Arm 3f

TYPHIM Vi (Salmonella typhi vaccine) BIOLOGICAL

TYPHIM Vi (Typhoid Vi Polysaccharide Vaccine), produced by Sanofi Pasteur SA, for IM use, is a sterile solution containing the cell surface Vi polysaccharide extracted from Salmonella enterica serovar Typhi, S typhi Ty2 strain (inactivated, subunit vaccine). TYPHIM Vi vaccine is indicated for active immunization for the prevention of typhoid fever caused by S typhi and is FDA approved for use in persons 2 years of age or older

Arm 3f

Menactra BIOLOGICAL

Menactra (Sanofi Pasteur) is a sterile, intramuscularly administered vaccine that contains Neisseria meningitidis serogroup A, C, Y, and W-135 capsular polysaccharide antigens individually conjugated to diphtheria toxoid protein. No preservative or adjuvant is added during the manufacturing process. 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.

Arm 1b/3d; Arm 2b/3b; Arm 3f

AVAXIM BIOLOGICAL

AVAXIM - Pediatric \[Hepatitis A Vaccine Inactivated\] is a sterile, whitish, cloudy suspension. The active ingredient is a purified and formaldehyde-inactivated hepatitis A virus (HAV) obtained from the GBM strain, cultured on MRC-5 human diploid cells. HAV is adsorbed onto aluminum.

Arm 1a/3c

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All of the following criteria must be fulfilled for a volunteer to participate in this trial:
• Meets age requirements for Arm currently being enrolled.
• Available for the duration of the trial.
• Family compound known resident or long-term resident (more than 1 year) of Doneguebougou, Mali or surrounding villages.
• 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 from 21 days prior to Study Day 0 and until 1 month after the last vaccination.
• A reliable method of birth control includes one of the following:
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• Confirmed pharmacologic contraceptives (parenteral) delivery;
• Intrauterine or implantable device
• EXCEPTIONS to required pregnancy prevention includes the following:
• Postmenopausal state: defined as no menses for 12 months without an alternative medical cause
• Surgical sterilization
• Unmarried AND not sexually active AND menstruating OR not menstruating females 12-17 years of age

You may not qualify if:

• An individual will be excluded from participating in this trial if any one of the following criteria is fulfilled:
• Pregnant, as determined by a positive urine or serum beta human choriogonadotropin (beta-hCG) test (if female).
• NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing
• Menstruating females 11 years of age and younger. (In order to avoid cultural implications of further assessing pregnancy potential i.e. sexual activity in this age group.)
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol at a level appropriate for the subject s age.
• Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels 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 \<= Grade 2.)
• 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 \<= Grade 2.)
• Infected with HIV
• 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.
• Clinically significant prolonged QTc (\>450 milliseconds) on screening EKG
• History of receiving any investigational product within the past 30 days.
• Current or planned participation in an investigational vaccine study until the last required protocol visit.
• 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.
• Known:

Sponsors & Collaborators

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

Study Sites (1)

Mrtc/Usttb

Bamako, Mali

Location

Related Publications (4)

• MacDonald NJ, Nguyen V, Shimp R, Reiter K, Herrera R, Burkhardt M, Muratova O, Kumar K, Aebig J, Rausch K, Lambert L, Dawson N, Sattabongkot J, Ambroggio X, Duffy PE, Wu Y, Narum DL. Structural and Immunological Characterization of Recombinant 6-Cysteine Domains of the Plasmodium falciparum Sexual Stage Protein Pfs230. J Biol Chem. 2016 Sep 16;291(38):19913-22. doi: 10.1074/jbc.M116.732305. Epub 2016 Jul 18.

  PMID: 27432885 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

• 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

• 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

Hepatitis A Vaccines; Vi polysaccharide vaccine, typhoid; Meningococcal Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Bacterial Vaccines

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: Yes

Study Design

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

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 17, 2019
• Study Start: April 24, 2019
• Primary Completion: July 30, 2021
• Study Completion: October 31, 2022
• Last Updated: October 22, 2024
• Results First Posted: August 23, 2022

Record last verified: 2021-12

Locations

MA (1)