This is a Phase 1, individually randomized, double-blind, dose escalating study designedto evaluate the safety, tolerability, and immunogenicity of Pfs230D1 conjugate vaccines,R21 nanoparticle vaccine, or their combination conjugate vaccines, formulated on Matrix-Min healthy African adults aged 18 to 50 years.
240 healthy adults (18-50 years of age) will be enrolled from Mali, Africa in a staggered
manner by increasing Pfs230D1 dosing.
Participants will be randomized by cohorts as (detailed below) to one of the study arms
to receive single antigen (Pfs230D1 or R21) or combination (Pfs230D1 + R21) with 50 μg of
Matrix-M, all administered as an IM injection on a 1, 29, 57-day schedule. Participants
will be followed for safety for 6 months post last dose with continued assessment for
clinical malaria cases and immunogenicity up until 12 months post last dose.
Cohort 1 (n=120); 1:1:1:1:1:1
- Arm 1a (n=20): 6μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
- Arm 1b (n=20): 6μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
- Arm 1c (n=20): 12μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
- Arm 1d (n=20): 12μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
- Arm 1e (n=20): 5μg of R21 in 50μg Matrix-M
- Arm 1f (n=20): 10μg of R21 in 50μg Matrix-M
Followed by Cohort 2 (n=80); 1:1:1:1
- Arm 2a (n=20): 20μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
- Arm 2b (n=20): 20μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
- Arm 2c (n=20): 20μg Pfs230D1-CRM197 in 50μg Matrix-M
- Arm 2d (n=20): 20μg Pfs230D1-EPA + 5μg of R21 in 50μg Matrix-M
Followed by Cohort 3 (n=40); 1:1
- Arm 3a (n=20): 40μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
- Arm 3b (n=20): 40μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
Biological: R21
R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in
the form of non-infectious virus-like particles (VLPs) produced in yeast cells
(Hansenula) by recombinant DNA technology.
Biological: Pfs230D1-CRM197
Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes,
gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted
with 50μg of Matrix-M.
Biological: Pfs230D1-EPA
Recombinant Pfs230D1 conjugated to a recombinant Pseudomonas aeruginosa ExoProtein A
(EPA)
Other: Matrix-M
Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and
cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for
vaccinations.
Inclusion Criteria:
1. Age: 18 to 50 years old.
2. Provides written informed consent.
3. Able to understand and comply with planned study procedures and be available for the
duration of the trial.
4. In good general health and without clinically significant medical history in the
opinion of the investigator.
5. Females of childbearing potential must be willing to use reliable contraception from
21 days prior to Study Day 1 and until 1 month after the last vaccination.
Exclusion Criteria:
1. Pregnant and breastfeeding females.
2. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels
outside the local laboratory-defined reference ranges.
3. Alanine transaminase (ALT) or creatinine (Cr) level above the local
laboratory-defined upper limit of reference range.
4. Infected with HIV, hepatitis B, hepatitis C.
5. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by
history, physical examination, and/or laboratory studies.
6. Current or planned participation in an investigational product study until the time
period of the last required study visit under this protocol.
7. Medical, occupational, or family problems as a result of alcohol or illicit drug use
during the past 12 months.
8. History of a severe allergic reaction or anaphylaxis.
9. Known: Severe asthma, Autoimmune or antibody-mediated disease, Immunodeficiency,
Seizure disorder, Asplenia or functional asplenia, Use of chronic oral or
intravenous corticosteroids (excluding topical or nasal), Sickle cell disease.
10. Any other condition that in the opinion of the investigator might jeopardize the
safety or rights of a subject participating in the trial, interfere with the
evaluation of the study objectives, or might render the subject unable to comply
with the protocol.
University of Science, Technique and Technology of Bamako (Usttb)
Bamako 2460596, Mali
Not Provided