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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

Primary Purpose

Malaria

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pvs230D1-EPA/Matrix-M
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring TBV, Open Label, Antibody, Reactogencity, Mosquito

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

5 (micro)g Pvs230D1-EPA/50 (micro)g MM

25 (micro)g Pvs230D1-EPA/50 (micro)g MM

50 (micro)g Pvs230D1-EPA/50 (micro)g MM

Outcomes

Primary Outcome Measures

To assess the safety and reactogenicity of Pvs230D1-EPA/MM in healthy malaria-naive adults
Incidence and severity of local and systemic adverse events (AEs) or serious adverse events (SAEs)

Secondary Outcome Measures

Full Information

First Posted
June 19, 2023
Last Updated
October 14, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT05913973
Brief Title
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
Official Title
Phase 1 Dose Escalation 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 Type
Interventional

2. Study Status

Record Verification Date
October 12, 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2023 (Actual)
Primary Completion Date
May 15, 2025 (Anticipated)
Study Completion Date
May 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Background: Malaria is a disease carried by mosquitoes in tropical countries around the world. It can cause symptoms like fever, body aches, and weakness. More than half a million people worldwide died of malaria in 2021, mostly children. Researchers want to find ways to prevent the spread of this disease. Objective: To test the effects of a new malaria vaccine. (Volunteers will not be exposed to malaria.) Eligibility: Healthy adults aged 18 to 50 years. Design: Volunteers will be screened. They will have a physical exam with blood and urine tests. They will take a short quiz to make sure they understand the study. Volunteers will have 3 visits to receive the vaccine. These visits will be about 1 month apart. The vaccine will be injected into the muscle of the upper arm. Volunteers will have 12 additional clinic visits. These will start after the first vaccine visit and continue for 8 months. The visits may include a physical exam and blood tests. There will also be 7 follow-up phone calls. These will occur the day after each vaccine visit and then continue for another 12 months. Participants will be asked how they are doing and whether they have had any changes in their health.
Detailed Description
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
TBV, Open Label, Antibody, Reactogencity, Mosquito

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
5 (micro)g Pvs230D1-EPA/50 (micro)g MM
Arm Title
Group 2
Arm Type
Experimental
Arm Description
25 (micro)g Pvs230D1-EPA/50 (micro)g MM
Arm Title
Group 3
Arm Type
Experimental
Arm Description
50 (micro)g Pvs230D1-EPA/50 (micro)g MM
Intervention Type
Drug
Intervention Name(s)
Pvs230D1-EPA/Matrix-M
Intervention Description
Pvs230 domain 1 (Pvs230D1) is a recombinant protein consisting of subdomain 1 of native Pvs230 (Val-226 to Gly-427, Figure 2) produced in Pichia pastoris. The synthetic gene sequence was optimized for P. pastoris expression and cloned into the expression vector pPICZ(alpha)A, which also encodes a pre-prosecretory alpha-factor sequence.
Primary Outcome Measure Information:
Title
To assess the safety and reactogenicity of Pvs230D1-EPA/MM in healthy malaria-naive adults
Description
Incidence and severity of local and systemic adverse events (AEs) or serious adverse events (SAEs)
Time Frame
Receipt of first vaccine through subject study completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joel A Goldberg, M.D.
Phone
(240) 292-4138
Email
joel.goldberg@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joel A Goldberg, M.D.
Organizational Affiliation
National Institute of Allergy and Infectious Diseases (NIAID)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joel Goldberg, M.D.
Phone
240-292-4138
Email
joel.goldberg@nih.gov

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
.This study will be conducted in accordance with the following publication and data sharing policies and regulations:@@@@@@NIH Public Access Policy, which ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication.@@@@@@This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals. @@@@@@
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001501-I.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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