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A Study of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in the UK

Primary Purpose

Malaria, Plasmodium Falciparum

Status
Recruiting
Phase
Early Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Pfs48/45 in Matrix-M
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring Pfs48/45, Matrix-M

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy adult aged 18 to 45 years.
  • Able and willing (in the Investigator's opinion) to comply with all study requirements.
  • Willing to allow the Investigators to discuss the volunteer's medical history with their GP.
  • Volunteers with the potential to become pregnant only: must practice continuous effective contraception for the duration of the study (see section 10.10).
  • Agreement to refrain from blood donation for the duration of the study.
  • Able and willing to provide written informed consent to participate in the trial

Exclusion Criteria:

  • History of clinical malaria (any species).
  • Travel to a clearly malaria endemic locality during the study period or within the preceding six months.
  • Use of immunoglobulins or blood products (e.g., blood transfusion) in the last three months.
  • Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination.
  • Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
  • Concurrent involvement in another clinical trial or planned involvement during the study period.
  • Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator.
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
  • Any history of anaphylaxis in reaction to vaccinations.
  • Pregnancy, lactation or intention to become pregnant during the study.
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
  • History of serious psychiatric condition that may affect participation in the study.
  • Any other serious chronic illness requiring hospital specialist supervision.
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 25 standard UK units every week.
  • Suspected or known injecting drug abuse in the 5 years preceding enrolment.
  • Hepatitis B surface antigen (HBsAg) detected in serum.
  • Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless volunteer has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV ribonucleic acid (RNA) PCR at screening for this study).
  • Volunteers unable to be closely followed for social, geographic or psychological reasons.
  • Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027.
  • Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
  • Inability of the study team to contact the volunteer's GP to confirm medical history

Sites / Locations

  • CCVTM, University of OxfordRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group 1 - low dose

Group 2 - standard dose

Group 3 - fractional dose

Arm Description

8-10 volunteers receiving three doses of 10 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm

8-10 volunteers receiving three doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm

8-10 volunteers receiving two doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0 and 28, followed by one dose of 10 µg Pfs48/45 in 50 µg Matrix-M on day 56 via intramuscular injection (IM) in the deltoid region of the arm

Outcomes

Primary Outcome Measures

To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers by assessing the occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers by assessing the occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination
Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers by assessing the occurrence of unsolicited adverse events (AEs) for 28 days following the vaccination
Occurrence of unsolicited adverse events (AEs) for 28 days following the vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers. assessed through the number of participants with abnormal laboratory test results
Occurrence of change from baseline laboratory tests
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers assessed through the number of participants with serious adverse events
Occurrence of serious adverse events and will be presented according to local grading scales
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers.
Occurrence of AEs of special interest and will be presented according to local grading scales and will be described in detail

Secondary Outcome Measures

To assess the humoral immunogenicity of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers as assessed by humoral responses to the Pfs48/45 protein
Antibody responses to the Pfs48/45 protein will be assessed through total IgG isotypes and avidity
To assess the cellular immunogenicity of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers as assessed by cellular responses to the Pfs48/45 protein
T cell responses to Pfs48/45 will be assessed by ex vivo enzyme-linked immunospot assays (ELISpot)
To assess ex vivo efficacy of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers using direct membrane feeding assays as assessed by transmission-reducing activity
Transmission-reducing activity
To assess ex vivo efficacy of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers using direct membrane feeding assays as assessed by transmission-blocking activity
Transmission-blocking activity

Full Information

First Posted
May 26, 2022
Last Updated
December 13, 2022
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT05400746
Brief Title
A Study of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in the UK
Official Title
A Phase Ia Study to Assess Safety and Immunogenicity of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in Healthy Adults Living in the UK
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 2, 2022 (Actual)
Primary Completion Date
May 30, 2023 (Anticipated)
Study Completion Date
May 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

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

5. Study Description

Brief Summary
This is an open label, single-site, first-in-human, dose-escalation Phase Ia study to assess safety and immunogenicity of the Plasmodium falciparum malaria vaccine candidate Pfs48/45 in Matrix-M adjuvant in healthy adults living in the UK
Detailed Description
Volunteers will be recruited into one of three groups (n=8-10 per group) at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford over approximately 12 months. All volunteers will receive three dose of Pfs48/45 in 50 µg Matrix-M, administered intramuscularly and given four weeks apart. Enrolment will be staggered with clinical and safety reviews, follow-up visits and monitoring via a diary card.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Plasmodium Falciparum
Keywords
Pfs48/45, Matrix-M

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Group 1 - low dose
Arm Type
Experimental
Arm Description
8-10 volunteers receiving three doses of 10 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm
Arm Title
Group 2 - standard dose
Arm Type
Experimental
Arm Description
8-10 volunteers receiving three doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm
Arm Title
Group 3 - fractional dose
Arm Type
Experimental
Arm Description
8-10 volunteers receiving two doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0 and 28, followed by one dose of 10 µg Pfs48/45 in 50 µg Matrix-M on day 56 via intramuscular injection (IM) in the deltoid region of the arm
Intervention Type
Biological
Intervention Name(s)
Pfs48/45 in Matrix-M
Intervention Description
Three doses of Pfs48/45 in Matrix-M at different doses
Primary Outcome Measure Information:
Title
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers by assessing the occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination
Description
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
Time Frame
7 days following each vaccination
Title
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers by assessing the occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination
Description
Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
Time Frame
7 days following each vaccination
Title
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers by assessing the occurrence of unsolicited adverse events (AEs) for 28 days following the vaccination
Description
Occurrence of unsolicited adverse events (AEs) for 28 days following the vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
Time Frame
28 days following the vaccination
Title
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers. assessed through the number of participants with abnormal laboratory test results
Description
Occurrence of change from baseline laboratory tests
Time Frame
28 days following vaccination
Title
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers assessed through the number of participants with serious adverse events
Description
Occurrence of serious adverse events and will be presented according to local grading scales
Time Frame
Whole duration of the study (8 months following initial trial vaccination)
Title
To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers.
Description
Occurrence of AEs of special interest and will be presented according to local grading scales and will be described in detail
Time Frame
Whole duration of the study (8 months following initial trial vaccination)
Secondary Outcome Measure Information:
Title
To assess the humoral immunogenicity of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers as assessed by humoral responses to the Pfs48/45 protein
Description
Antibody responses to the Pfs48/45 protein will be assessed through total IgG isotypes and avidity
Time Frame
Days 1, 29, 57, 140 and 240
Title
To assess the cellular immunogenicity of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers as assessed by cellular responses to the Pfs48/45 protein
Description
T cell responses to Pfs48/45 will be assessed by ex vivo enzyme-linked immunospot assays (ELISpot)
Time Frame
Days 1, 29, 57, 140 and 240
Title
To assess ex vivo efficacy of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers using direct membrane feeding assays as assessed by transmission-reducing activity
Description
Transmission-reducing activity
Time Frame
Days 1, 29, 57, 140 and 240
Title
To assess ex vivo efficacy of the Pfs48/45 with Matrix-M vaccine, when administered to healthy adult volunteers using direct membrane feeding assays as assessed by transmission-blocking activity
Description
Transmission-blocking activity
Time Frame
Days 1, 29, 57, 140 and 240

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy adult aged 18 to 45 years. Able and willing (in the Investigator's opinion) to comply with all study requirements. Willing to allow the Investigators to discuss the volunteer's medical history with their GP. Volunteers with the potential to become pregnant only: must practice continuous effective contraception for the duration of the study (see section 10.10). Agreement to refrain from blood donation for the duration of the study. Able and willing to provide written informed consent to participate in the trial Exclusion Criteria: History of clinical malaria (any species). Travel to a clearly malaria endemic locality during the study period or within the preceding six months. Use of immunoglobulins or blood products (e.g., blood transfusion) in the last three months. Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination. Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. Concurrent involvement in another clinical trial or planned involvement during the study period. Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Any history of anaphylaxis in reaction to vaccinations. Pregnancy, lactation or intention to become pregnant during the study. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). History of serious psychiatric condition that may affect participation in the study. Any other serious chronic illness requiring hospital specialist supervision. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 25 standard UK units every week. Suspected or known injecting drug abuse in the 5 years preceding enrolment. Hepatitis B surface antigen (HBsAg) detected in serum. Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless volunteer has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV ribonucleic acid (RNA) PCR at screening for this study). Volunteers unable to be closely followed for social, geographic or psychological reasons. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027. Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. Inability of the study team to contact the volunteer's GP to confirm medical history
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Volunteer Recruitment Co-ordinator Volunteer Recruitment Co-ordinator
Phone
01865 611424
Email
vaccinetrials@ndm.ox.ac.uk
Facility Information:
Facility Name
CCVTM, University of Oxford
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

A Study of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in the UK

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