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A Study to Determine if a New Malaria Vaccine is Safe and Induces Immunity Among Kenyan Adults, Young Children and Infants

Primary Purpose

Malaria,Falciparum

Status
Completed
Phase
Phase 1
Locations
Kenya
Study Type
Interventional
Intervention
R21 in Matrix- M adjuvant vaccine
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malaria,Falciparum

Eligibility Criteria

5 Months - 45 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy adults aged 18 to 45 years (Group 1), Healthy child aged 1-5 years (Group 2), healthy infant aged 5- <12 months (Group 3)
  • Able and willing (in the Investigator's opinion) to comply with all study requirements
  • Non-pregnant, non-lactating adult female or adult male
  • Agreement to refrain from blood donation during the study
  • Use of effective method of contraception for duration of study for female participants.

For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject's entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository)

  • Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or young children and infants with Z-score of weight-for-age within ±2SD
  • Provide written informed consent
  • Plan to remain resident in the study area for 2 years following last dose of vaccination

Exclusion Criteria:

  • Clinically significant congenital abnormalities as judged by the study clinician.
  • 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).
  • Sickle cell trait or disease or G6PD deficiency.
  • Any history of anaphylaxis in relation to vaccination.
  • Clinically significant laboratory abnormality as judged by the study clinician.
  • Blood transfusion within one month of enrolment.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
  • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
  • Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG).
  • Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Sites / Locations

  • KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast

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

Group 1 adults (n=20) will be administered 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the non-dominant arm). A booster dose will be administered at 9-25 months post 3rd dose.

Group 2A children 1-5 years (n=3) will be receiving 5mcg R21/25mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 2B children 1-5 years (n=17) will be receiving 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). A booster dose will be administered at 9-25 months post 3rd dose.

Group 3A infants 5-<12 months (n=3) will be receiving 5mcg R21/25mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3B infants 5-<12 months (n=3) will be receiving 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3C infants 5-<12 months (n=15) will be receiving 5mcg R21/25mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3D infants 5-<12 months (n=15) will be receiving 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3E infants 5-<12 months (n=15) will be receiving 5mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). A booster dose will be administered at 9-25 months post 3rd dose.

Outcomes

Primary Outcome Measures

To evaluate the safety and tolerability of R21 with adjuvant Matrix-M in healthy adults then children and finally infants.
Solicited and unsolicited adverse event data will be collected at each clinic visit from diary cards, clinical review, clinical examination (including observations) and laboratory results. This AE data will be tabulated and frequency, duration and severity of AEs compared between groups. The following parameters will be assessed for all study groups: Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination Occurrence of unsolicited adverse events for 28 days following the vaccination Change from baseline for safety laboratory measures Occurrence of serious adverse events during the whole study duration

Secondary Outcome Measures

To assess the cellular and humoral immunogenicity of R21 in humans with adjuvant Matrix- M in healthy adults, children and infants.
Comparison of immunogenicity (antibody responses) of the R21-Matrix-M1 - adjuvanted vaccination doses and the longevity of responses. ELISA to quantify antibodies to the vaccine components CS, NANP and HBsAb. Flow cytometry assays with intracellular cytokine staining to enumerate and functionally characterise immune cell populations such as effector and memory T cells (e.g. CD4+ and CD8+), T follicular helper cells, regulatory T cells, B cells, plasma cells and dendritic cells ELISPOT for enumeration of antibody-secreting cells (e.g. B and plasma cells)

Full Information

First Posted
June 11, 2018
Last Updated
July 31, 2023
Sponsor
University of Oxford
Collaborators
Kenya Medical Research Institute, European and Developing Countries Clinical Trials Partnership (EDCTP)
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1. Study Identification

Unique Protocol Identification Number
NCT03580824
Brief Title
A Study to Determine if a New Malaria Vaccine is Safe and Induces Immunity Among Kenyan Adults, Young Children and Infants
Official Title
A Phase 1b, Open-label, Age De-escalation, Dose-escalation Study to Evaluate the Safety and Immunogenicity of Different Doses of a Candidate Malaria Vaccine; Adjuvanted R21(R21/MM) in Adults, Young Children and Infants in Kilifi, Kenya
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
April 30, 2019 (Actual)
Primary Completion Date
June 14, 2022 (Actual)
Study Completion Date
June 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Kenya Medical Research Institute, European and Developing Countries Clinical Trials Partnership (EDCTP)

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 a clinical trial to evaluate the safety and immunogenicity of R21/MM in healthy Kenyan participants from the different age groups.Participants will receive 3 vaccinations 4 weeks apart.
Detailed Description
The study includes three age groups: Group 1: healthy adults (18-45 years) Group 2: young children (aged 1-5 years) Group 3: infants (aged 5- <12 months of age) Each group will receive 3 vaccine doses which will be 4-weeks apart. A booster dose will be administered at 9-25 months post 3rd dose. The trial is funded by The European & Developing Countries Clinical Trials Partnership (EDCTP), European Union, ref: RIA2016V-1649 MMVC

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria,Falciparum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
Group 1 adults (n=20) will be administered 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the non-dominant arm). A booster dose will be administered at 9-25 months post 3rd dose.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Group 2A children 1-5 years (n=3) will be receiving 5mcg R21/25mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 2B children 1-5 years (n=17) will be receiving 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). A booster dose will be administered at 9-25 months post 3rd dose.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Group 3A infants 5-<12 months (n=3) will be receiving 5mcg R21/25mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3B infants 5-<12 months (n=3) will be receiving 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3C infants 5-<12 months (n=15) will be receiving 5mcg R21/25mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3D infants 5-<12 months (n=15) will be receiving 10mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). Group 3E infants 5-<12 months (n=15) will be receiving 5mcg R21/50mcg Matrix-M vaccine through intramuscular route (into the left deltoid). A booster dose will be administered at 9-25 months post 3rd dose.
Intervention Type
Biological
Intervention Name(s)
R21 in Matrix- M adjuvant vaccine
Intervention Description
R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant.
Primary Outcome Measure Information:
Title
To evaluate the safety and tolerability of R21 with adjuvant Matrix-M in healthy adults then children and finally infants.
Description
Solicited and unsolicited adverse event data will be collected at each clinic visit from diary cards, clinical review, clinical examination (including observations) and laboratory results. This AE data will be tabulated and frequency, duration and severity of AEs compared between groups. The following parameters will be assessed for all study groups: Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination Occurrence of unsolicited adverse events for 28 days following the vaccination Change from baseline for safety laboratory measures Occurrence of serious adverse events during the whole study duration
Time Frame
up to 2 years following vaccination
Secondary Outcome Measure Information:
Title
To assess the cellular and humoral immunogenicity of R21 in humans with adjuvant Matrix- M in healthy adults, children and infants.
Description
Comparison of immunogenicity (antibody responses) of the R21-Matrix-M1 - adjuvanted vaccination doses and the longevity of responses. ELISA to quantify antibodies to the vaccine components CS, NANP and HBsAb. Flow cytometry assays with intracellular cytokine staining to enumerate and functionally characterise immune cell populations such as effector and memory T cells (e.g. CD4+ and CD8+), T follicular helper cells, regulatory T cells, B cells, plasma cells and dendritic cells ELISPOT for enumeration of antibody-secreting cells (e.g. B and plasma cells)
Time Frame
up to 2 years following vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Months
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy adults aged 18 to 45 years (Group 1), Healthy child aged 1-5 years (Group 2), healthy infant aged 5- <12 months (Group 3) Able and willing (in the Investigator's opinion) to comply with all study requirements Non-pregnant, non-lactating adult female or adult male Agreement to refrain from blood donation during the study Use of effective method of contraception for duration of study for female participants. For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject's entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository) Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or young children and infants with Z-score of weight-for-age within ±2SD Provide written informed consent Plan to remain resident in the study area for 2 years following last dose of vaccination Exclusion Criteria: Clinically significant congenital abnormalities as judged by the study clinician. 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). Sickle cell trait or disease or G6PD deficiency. Any history of anaphylaxis in relation to vaccination. Clinically significant laboratory abnormality as judged by the study clinician. Blood transfusion within one month of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG). Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Hill
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast
City
Kilifi
ZIP/Postal Code
PO Box 230, 80108
Country
Kenya

12. IPD Sharing Statement

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A Study to Determine if a New Malaria Vaccine is Safe and Induces Immunity Among Kenyan Adults, Young Children and Infants

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