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Phase Ia Study of ChAd63/MVA PvDBP

Primary Purpose

Malaria, Plasmodium Vivax

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
ChAd63 PvDBP 5 x 10^9
ChAd63 PvDBP 5 x 10^10
MVA PvDBP 1 x 10^8
MVA PvDBP 2 x 10^8
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 PvDBP, Malaria, Plasmodium vivax

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy adults aged 18 to 50 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 General Practitioner.
  • For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of vaccination.

Agreement to refrain from blood donation during the course of the study.

-Provide written informed consent.

Exclusion Criteria:

  • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
  • Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
  • 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, e.g. egg products, Kathon.
  • History of clinically significant contact dermatitis.
  • Any history of anaphylaxis in reaction to vaccination.
  • Pregnancy, lactation or willingness/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.
  • Any other serious chronic illness requiring hospital specialist supervision.
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.
  • Suspected or known injecting drug abuse in the 5 years preceding enrolment.
  • Seropositive for hepatitis B surface antigen (HBsAg).
  • Seropositive for hepatitis C virus (antibodies to HCV) with positive PCR for hepatitis C at screening.
  • History of clinical malaria (any species).
  • Travel to a malaria endemic region during the study period or within the previous six months.
  • Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis.
  • 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 and safety to participate.

Sites / Locations

  • Centre for Clinical Vaccinology and Tropical Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 1

Group 2A

Group 2B

Group 2C

Arm Description

4 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^9 vp intramuscularly

4 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly

8 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly and 1 dose MVA PvDBP 1 x 10^8 pfu 8 weeks later intramuscularly

8 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly and 1 dose MVA PvDBP 2 x 10^8 pfu 8 weeks later intramuscularly

Outcomes

Primary Outcome Measures

The safety in healthy volunteers of two new candidate malaria vaccines, ChAd63 PvDBP administered alone, and with MVA PvDBP, in a prime-boost regime.
To assess the safety of ChAd63 PvDBP when administered alone and in heterologous prime-boost with MVA PvDBP. Safety will be assessed by the frequency, incidence and nature of adverse events and serious adverse events arising during the study as well as abnormalities in Hematology and Biochemistry lab tests.

Secondary Outcome Measures

The humoral and cellular immunogenicity of ChAd63 PvDBP, when administered to healthy volunteers alone and with MVA PvDBP.
PvDBP_RII-specific immunogenicity will be assessed by a variety of immunological assays. These may include ex vivo ELISpot assays for interferon gamma and flow cytometry assays, as well as antibody ELISAs. Other exploratory immunological assays including cytokine analysis, antibody assays, anti-adenovirus antibodies, DNA analysis of genetic polymorphisms potentially relevant to vaccine immunogenicity and gene expression studies amongst others may be performed at the discretion of the investigators. Other exploratory immunology may be carried out in collaboration with other specialist labs, including labs outside of Europe. This would involve transfer of serum/plasma, but samples will be anonymised. Volunteers will be consented beforehand.

Full Information

First Posted
March 13, 2013
Last Updated
May 5, 2017
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT01816113
Brief Title
Phase Ia Study of ChAd63/MVA PvDBP
Official Title
A Phase Ia Clinical Trial to Assess the Safety and Immunogenicity of New Plasmodium Vivax Malaria Vaccine Candidates ChAd63 PvDBP Alone and With MVA PvDBP
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an open label phase Ia study, to assess the safety of two novel malaria vaccines, ChAd63 PvDBP, with or without MVA PvDBP. Heterologous prime-boost with ChAd63-MVA is, to our knowledge, one of the most potent T cell-inducing subunit vaccine regimens which can importantly also induce antibodies. Previous clinical trials using this regimen expressing ME-TRAP, AMA1 & MSP1, have shown that administering ChAd63 as a prime followed 8 weeks later by MVA as a boost is a very immunogenic schedule (32-34). For this reason, and to provide comparability with previous ChAd63-MVA trials, we propose to use a similar administration schedule.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Plasmodium Vivax
Keywords
PvDBP, Malaria, Plasmodium vivax

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Experimental
Arm Description
4 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^9 vp intramuscularly
Arm Title
Group 2A
Arm Type
Experimental
Arm Description
4 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly
Arm Title
Group 2B
Arm Type
Experimental
Arm Description
8 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly and 1 dose MVA PvDBP 1 x 10^8 pfu 8 weeks later intramuscularly
Arm Title
Group 2C
Arm Type
Experimental
Arm Description
8 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly and 1 dose MVA PvDBP 2 x 10^8 pfu 8 weeks later intramuscularly
Intervention Type
Biological
Intervention Name(s)
ChAd63 PvDBP 5 x 10^9
Intervention Description
1 dose of ChAd63 PvDBP 5 x 10^9 vp intramuscularly
Intervention Type
Biological
Intervention Name(s)
ChAd63 PvDBP 5 x 10^10
Intervention Description
1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly
Intervention Type
Biological
Intervention Name(s)
MVA PvDBP 1 x 10^8
Intervention Description
1 dose MVA PvDBP 1 x 108 pfu 8 weeks later intramuscularly
Intervention Type
Biological
Intervention Name(s)
MVA PvDBP 2 x 10^8
Intervention Description
1 dose MVA PvDBP 2 x 108 pfu 8 weeks later intramuscularly
Primary Outcome Measure Information:
Title
The safety in healthy volunteers of two new candidate malaria vaccines, ChAd63 PvDBP administered alone, and with MVA PvDBP, in a prime-boost regime.
Description
To assess the safety of ChAd63 PvDBP when administered alone and in heterologous prime-boost with MVA PvDBP. Safety will be assessed by the frequency, incidence and nature of adverse events and serious adverse events arising during the study as well as abnormalities in Hematology and Biochemistry lab tests.
Time Frame
Up to 20 weeks post first vaccination
Secondary Outcome Measure Information:
Title
The humoral and cellular immunogenicity of ChAd63 PvDBP, when administered to healthy volunteers alone and with MVA PvDBP.
Description
PvDBP_RII-specific immunogenicity will be assessed by a variety of immunological assays. These may include ex vivo ELISpot assays for interferon gamma and flow cytometry assays, as well as antibody ELISAs. Other exploratory immunological assays including cytokine analysis, antibody assays, anti-adenovirus antibodies, DNA analysis of genetic polymorphisms potentially relevant to vaccine immunogenicity and gene expression studies amongst others may be performed at the discretion of the investigators. Other exploratory immunology may be carried out in collaboration with other specialist labs, including labs outside of Europe. This would involve transfer of serum/plasma, but samples will be anonymised. Volunteers will be consented beforehand.
Time Frame
U to 20 weeks post first vaccination.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy adults aged 18 to 50 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 General Practitioner. For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of vaccination. Agreement to refrain from blood donation during the course of the study. -Provide written informed consent. Exclusion Criteria: Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. Prior receipt of an investigational malaria vaccine or any other investigational vaccine likely to impact on interpretation of the trial data. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. 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, e.g. egg products, Kathon. History of clinically significant contact dermatitis. Any history of anaphylaxis in reaction to vaccination. Pregnancy, lactation or willingness/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. Any other serious chronic illness requiring hospital specialist supervision. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. Suspected or known injecting drug abuse in the 5 years preceding enrolment. Seropositive for hepatitis B surface antigen (HBsAg). Seropositive for hepatitis C virus (antibodies to HCV) with positive PCR for hepatitis C at screening. History of clinical malaria (any species). Travel to a malaria endemic region during the study period or within the previous six months. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis. 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 and safety to participate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian V S Hill, MD
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Clinical Vaccinology and Tropical Medicine
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28614791
Citation
Payne RO, Silk SE, Elias SC, Milne KH, Rawlinson TA, Llewellyn D, Shakri AR, Jin J, Labbe GM, Edwards NJ, Poulton ID, Roberts R, Farid R, Jorgensen T, Alanine DG, de Cassan SC, Higgins MK, Otto TD, McCarthy JS, de Jongh WA, Nicosia A, Moyle S, Hill AV, Berrie E, Chitnis CE, Lawrie AM, Draper SJ. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight. 2017 Jun 15;2(12):e93683. doi: 10.1172/jci.insight.93683. eCollection 2017 Jun 15.
Results Reference
derived

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Phase Ia Study of ChAd63/MVA PvDBP

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