Study of the Plasmodium Vivax Transmission-blocking Vaccine Pvs230D1-EPA/Matrix-M to Assess Safety, Immunogenicity, and Transmission-blocking Activity in Healthy Malaria-naive Adults

Study Description:

Single-center, open-label, first-in-human, dose-escalating phase 1 study to characterize the safety, immunogenicity, and transmission-blocking activity in healthy malaria-naive adults of the Plasmodium vivax (P. vivax) transmission-blocking vaccine (TBV), Pvs230D1-EPA combined with adjuvant Matrix-M (MM). Three doses of vaccine will be administered at 1-month intervals (study days 0, 28, and 56). Subjects will be divided into low, intermediate, and high dose groups based on the amount of the antigen component in each vaccine dose:

• Group 1 (n = 10): 5 (micro)g Pvs230D1-EPA/50 (micro)g MM
• Group 2 (n = 10): 25 (micro)g Pvs230D1-EPA/50 (micro)g MM
• Group 3 (n = 10): 50 (micro)g Pvs230D1-EPA/50 (micro)g MM

Objectives:

Primary Objective

-To assess the safety and reactogenicity of Pvs230D1-EPA/MM in healthy malaria-naive adults

Exploratory Objectives

• To determine the antibody response to Pvs230D1-EPA/MM
• To determine the functional response to Pvs230D1-EPA/MM by mosquito feeding assays
• To assess cellular and transcriptomic responses to Pvs230D1-EPA/MM
• To identify and characterize human monoclonal antibodies (mAbs) with activity against Pvs230D1M

Endpoints:

Primary Endpoint

-Incidence and severity of local and systemic adverse events (AEs) or serious adverse events (SAEs)

Exploratory Endpoints

• Anti-Pvs230D1M antibody levels as measured by enzyme-linked immunosorbent assay (ELISA)
• Transmission-reducing activity (TRA) and/or transmission-blocking activity (TBA) of Pvs230D1-EPA/MM using direct membrane feeding assays (DMFA)
• Cellular immune responses and whole genome transcriptional profiles
• Isolation of reactive antibodies from sorted B cells

• INCLUSION CRITERIA:

All of the following criteria must be fulfilled for a subject to participate in this trial:

• Age >=18 and <=50 years.
• In good general health and without clinically significant medical history.
• Able to sign a written informed consent prior to undertaking any study-related procedure.
• Vaccine comprehension exam completed, passed (a score of (Bullet)80% or per investigator s discretion), and reviewed prior to enrollment.
• Suitable accommodation and reliable access to the NIHCC for the duration of the study, in the opinion of the investigator.
• Individuals of childbearing potential must agree to use an acceptable method of contraception from 1 month prior to enrollment to 1 month after the final vaccination (i.e., from study day -28 until study day 84).
• Individuals capable of fathering children must agree to use an acceptable method of contraception from 1 month prior to enrollment to 1 month after the final vaccination (i.e., from study day -28 until study day 84).
• Willing to allow long-term storage of study samples for future research.
• Willing to refrain from donating blood throughout the study until 6 months after the last vaccination.

Exclusion criteria

A subject will be excluded from participating in this trial if any 1 of the following criteria is fulfilled:

• Planned travel to a malaria-endemic area until 6-months beyond the final vaccination (see https://www.cdc.gov/malaria/travelers/country_table/a.html). Exceptions may be made, at the investigator s discretion, if the travel is limited to areas without appreciable levels of P. vivax transmission.
• Any prior confirmed P. vivax malaria diagnosis or clinical history consistent with P. vivax malaria diagnosis within the previous 10 years, at the investigator's discretion.
• Any subject without good peripheral venous access, at the investigator's discretion.
• For individuals of childbearing potential:

• Currently breastfeeding.
• Currently pregnant as determined by history or a positive human choriogonadotropin (beta-hCG) test.
• Clinical trial staff with direct involvement in the conduct of the trial are excluded from participation.
• HIV, hepatitis B, and/or hepatitis C as determined by HIV antigen/antibody, Hepatitis B surface antigen, and anti-Hepatitis C antibody laboratory tests.
• Screening blood test or urinalysis laboratory parameters outside of local lab normal range. Subjects may be included at the investigator s discretion for "not clinically significant" values outside of normal range.
• History of anaphylaxis, severe allergy, or other concerning adverse reaction, in the opinion of the investigator, to a previous vaccine.
• Any of the following within the specified periods:

• Investigational P. vivax malaria vaccine within the last 2 years.
• Chronic systemic immunosuppressive medications (>14 days) within 6 months of study day 0 (e.g., cytotoxic medications, adrenocorticotrophic hormone, or oral/parental corticosteroids equivalent to >0.5 mg/kg/day of prednisone). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed at the discretion of the investigator.
• Investigational or non-FDA approved/authorized product or vaccine within 28 days prior to study day 0.
• Asplenia or functional asplenia.
• Blood transfusion or IVIG within 6 months of study day 0.
• Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a subject s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study.

Subjects who are excluded from participation for any of the reasons above may be considered for

enrollment on a postponed schedule if the investigator considers this appropriate.

Subjects will be selected in an equitable manner from the available pool of potentially eligible individuals, without regard to factors such as sex, gender, race, ethnicity, socioeconomic status, etc., except for age.