Study of the Transmission-Blocking Vaccine Pfs230D1-EPA/Matrix-M Against Malaria in Adults in Mali

NCT05135273 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: N°2021/210/CE/USTTB000576
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Researchers are trying to develop a vaccine that will safely reduce the spread of malaria in the community by preventing mosquitos from carrying malaria from person to person. Objective: To assess in African adults the safety of and immune response to the administration of Pfs230D1-EPA/Matrix-M vaccine as compared to the rabies vaccine control. Eligibility: Healthy adults (18 to 50 years of age) who reside in Sotuba and surrounding villages in Mali Design: Participants will be screened with:

• Medical history
• Physical exam
• Blood, urine, and heart tests
• Malaria comprehension exam Participants will be randomly assigned to get either the experimental vaccine or the approved rabies vaccine. They will not know which they are getting. Participants will get 3 doses of the study or comparator vaccine via injection in the upper arm. This occurs at the first visit, 1 month, and 2 months later. Participants will have up to 23 scheduled visits over 14 to 16 months. Each visit includes a physical exam, and blood will be collected at most visits. Participants will be followed up to 1 year after the final vaccination. If participants develop an injection site rash or reaction, photographs may be taken of the site.

Conditions

Malaria,Falciparum

Keywords

Malaria; Reactogenicity; Antibody; Mosquito; Vaccine

Outcome Measures

Primary Outcomes (2)

• Number of Local and Systemic Adverse Events (AEs) to Assess the Safety of the Study Drug

  The analyses included only subjects who received at least one vaccination

  Adverse Events monitored/assessed for 7 days after each vaccination at days 1, 29, and 57; All-Cause Mortality monitored/assessed through 14 months

• Number of Local and Systemic Serious Adverse Events (SAEs) to Assess the Safety of the Study Drug

  Serious Adverse Events monitored/assessed for 7 days after each vaccination at days 1, 29, and 57; All-Cause Mortality monitored/assessed through 14 months

Study Arms (8)

1a (Pilot Group)

EXPERIMENTAL

(n=5) to receive 12.5 µg Pfs230D1-EPA/25 µg Matrix-M on D1, D29, D57

Biological: Pfs230D1-EPA/Matrix-M Vaccine

1b (Pilot Group)

EXPERIMENTAL

(n=5) to receive 20 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57

Biological: Pfs230D1-EPA/Matrix-M Vaccine

1c (Pilot Group)

EXPERIMENTAL

(n=5) to receive 40 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57

Biological: Pfs230D1-EPA/Matrix-M Vaccine

1d (Pilot Group)

ACTIVE COMPARATOR

(n=4) to receive rabies vaccine (standard dose) on D1, D29, D57

Biological: Verorab Rabies Vaccine

2a (Main Group)

EXPERIMENTAL

(n=15) to receive 12.5 µg Pfs230D1-EPA/25 µg Matrix-M on D1, D29, D57

Biological: Pfs230D1-EPA/Matrix-M Vaccine

2b (Main Group)

EXPERIMENTAL

(n=15) to receive 20 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57

Biological: Pfs230D1-EPA/Matrix-M Vaccine

2c (Main Group)

EXPERIMENTAL

(n=15) to receive 40 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57

Biological: Pfs230D1-EPA/Matrix-M Vaccine

2d (Main Group)

ACTIVE COMPARATOR

(n=16) to receive rabies vaccine (standard dose) on D1, D29, D57

Biological: Verorab Rabies Vaccine

Interventions

Pfs230D1-EPA/Matrix-M Vaccine BIOLOGICAL

Each single-use vial of Pfs230D1M-EPA contains 160 µg/mL of conjugated Pfs230D1M and 124 µg/mL or 143 µg/mL of conjugated EPA in 4 mM phosphate-buffered saline (PBS), in a volume of 0.5 mL. Each vial of Matrix-M1 contains saponin content of 0.375 mg/mL in PBS, at a pH of 7.2, in a final volume of 0.75 mL. Components will be combined in volumes defined in the protocol at point of use.

1a (Pilot Group); 1b (Pilot Group); 1c (Pilot Group); 2a (Main Group); 2b (Main Group); 2c (Main Group)

Verorab Rabies Vaccine BIOLOGICAL

Verorab Rabies Vaccine is a purified inactivated rabies vaccine (Wistar rabies PM/WI 38 1503-3M strain) prepared on Vero cells. It is supplied as a powder and solvent for suspension for injection in a prefilled syringe. Before reconstitution, the powder is a white and homogeneous pellet. The solvent is a limpid solution.

1d (Pilot Group); 2d (Main Group)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• 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: \> 18 years old and \< 50 years old.
• Available for the duration of the trial.
• Known resident or long-term resident (more than 1 year) of Sotuba, 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:
• 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.
• Willing to have blood samples stored for future research.

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 (β hCG) test (if female). NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing.
• 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.
• History of receiving any investigational product within the past 30 days.
• Current or planned participation in an investigational vaccine study until the time period of the last required study visit under this protocol.
• 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:
• 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.
• Autoimmune or antibody-mediated disease including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia.
• Immunodeficiency syndrome.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Novavax: collaborator
• Malaria Research and Training Center, Bamako, Mali: collaborator

Study Sites (1)

Malaria Research Training Center

Bamako, Mali

Location

Related Publications (4)

• Coelho CH, Tang WK, Burkhardt M, Galson JD, Muratova O, Salinas ND, Alves E Silva TL, Reiter K, MacDonald NJ, Nguyen V, Herrera R, Shimp R, Narum DL, Byrne-Steele M, Pan W, Hou X, Brown B, Eisenhower M, Han J, Jenkins BJ, Doritchamou JYA, Smelkinson MG, Vega-Rodriguez J, Truck J, Taylor JJ, Sagara I, Healy SA, Renn JP, Tolia NH, Duffy PE. A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes. Nat Commun. 2021 Mar 19;12(1):1750. doi: 10.1038/s41467-021-21955-1.

  PMID: 33741942 BACKGROUND

• Datoo MS, Natama MH, Some A, Traore O, Rouamba T, Bellamy D, Yameogo P, Valia D, Tegneri M, Ouedraogo F, Soma R, Sawadogo S, Sorgho F, Derra K, Rouamba E, Orindi B, Ramos Lopez F, Flaxman A, Cappuccini F, Kailath R, Elias S, Mukhopadhyay E, Noe A, Cairns M, Lawrie A, Roberts R, Valea I, Sorgho H, Williams N, Glenn G, Fries L, Reimer J, Ewer KJ, Shaligram U, Hill AVS, Tinto H. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021 May 15;397(10287):1809-1818. doi: 10.1016/S0140-6736(21)00943-0. Epub 2021 May 5.

  PMID: 33964223 BACKGROUND

• 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 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, Falciparum; Malaria

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. David Cook
• Organization: Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH

david.cook@nih.gov

240.627.3066

Study Officials

• Patrick Duffy, MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  STUDY CHAIR

• Issaka Sagara, MD

  Malaria Research and Training Center, Bamako, Mali

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• 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: November 17, 2021
• First Posted: November 26, 2021
• Study Start: October 22, 2021
• Primary Completion: February 17, 2023
• Study Completion: June 21, 2023
• Last Updated: May 6, 2024
• Results First Posted: May 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)