Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Determine if New Types of Malaria Vaccines Are Safe, Effective and Lead to Immunity in Kenyan Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03947190
Recruitment Status : Not yet recruiting
First Posted : May 13, 2019
Last Update Posted : August 18, 2020
Sponsor:
Collaborators:
Kenya Medical Research Institute
The European & Developing Countries Clinical Trials Partnership (EDCTP), European Union
Information provided by (Responsible Party):
University of Oxford

Brief Summary:
This is a phase IIb clinical trial in malaria-exposed individuals to assess the immunogenicity, safety and efficacy of the two vaccines in the context of controlled human malaria infection, P. falciparum sporozoite challenge (PfSPZ Challenge).

Condition or disease Intervention/treatment Phase
Malaria,Falciparum Biological: R21/Matrix-M Biological: ChAd63/MVA ME-TRAP Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge Phase 2

Detailed Description:

A total of 64 participants will be enrolled for challenge and divided into four groups as follows:

  • 20 participants to receive R21/Matrix M (R21/MM) with intradermal PfSPZ Challenge;
  • 20 participants to receive viral-vectored ME-TRAP with intradermal PfSPZ Challenge;
  • 10 participants to receive R21/MM with direct venous inoculation PfSPZ Challenge; and
  • 14 participants comprising of the control group with intradermal PfSPZ Challenge.

Blood tests and clinical assessments will be conducted to screen out participants with health conditions that may impact participation in the study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Immunogenicity, and Efficacy of R21/Matrix-M and ChAd63/MVA-ME-TRAP in the Context of Controlled Human Malaria Infection: A Phase IIb Trial in Kenyan Adults
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
Group 1 adults (n=20) will be receiving, 4 weeks apart, three doses of 10µg R21 /50µg Matrix M vaccine, and a CHMI intradermally (ID) by inoculation of 22,500 PfSPZ Challenge.
Biological: R21/Matrix-M
R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant.

Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.

Experimental: Group 2
Group 2 adults (n=20) will be receiving 5x10^10 vp ChAd63 ME-TRAP and 2x10^8 pfu MVA ME-TRAP vaccines, 8 weeks apart, and then a CHMI intradermally (ID) by inoculation of 22,500 PfSPZ Challenge, 4 weeks later.
Biological: ChAd63/MVA ME-TRAP
ChAd63, chimpanzee adenovirus serotype 63; ME-TRAP, multiple epitope string fused to the thrombospondin-related adhesion protein; MVA, modified vaccinia Ankara.

Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.

Experimental: Group 3
Group 3 adults (n=10) will be receiving, 4 weeks apart, three doses of 10µg R21 /50µg Matrix M vaccine, and a CHMI intravenously (DVI) by inoculation of 3,200 PfSPZ Challenge.
Biological: R21/Matrix-M
R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant.

Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.

Experimental: Group 4
Group 4 adults (n=14) will be the control group receiving no vaccine, only a CHMI intradermally (ID) by inoculation of 22,500 PfSPZ Challenge.
Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.




Primary Outcome Measures :
  1. Occurrence of solicited local and systemic reactogenicity signs and symptoms, and unsolicited adverse events [ Time Frame: Solicited AEs are collected for 7 days post vaccination and unsolicited AEs for 28 days post vaccination ]
    Assessing the safety and reactogenicity of adjuvanted R21/MM and heterologous prime- boost regime of ChAd63-MVA ME-TRAP in healthy adult volunteers

  2. Occurrence of P. falciparum parasitemia assessed by PCR, and parasite density dynamics assessed by PCR, against malaria sporozoite challenge [ Time Frame: up to 3 months after malaria sporozoite challenge ]
    To assess the safety of intradermal sporozoite infection dose in semi-immune healthy adult volunteers

  3. Occurrence of P. falciparum parasitemia, assessed by qPCR [ Time Frame: from vaccination day up to 90 days after malaria sporozoite challenge ]
    To assess the efficacy of adjuvanted R21 and heterologous prime- boost regime of ChAd63-MVA ME-TRAP against malaria sporozoite challenge, in healthy adult volunteers


Secondary Outcome Measures :
  1. To measure cellular immunogenicity assessed by ELISPOT [ Time Frame: from vaccination day up to 90 days after malaria sporozoite challenge ]
    Assessing cellular immunogenicity by ELISPOT to enumerate IFN-ƴ producing T cells

  2. To measure humoral immunogenicity assessed by ELISA [ Time Frame: from vaccination day up to 90 days after malaria sporozoite challenge ]
    Assessing humoral immunogenicity by ELISA to quantify antibodies to the vaccine components CS, NANP, TRAP and HBsAb.

  3. Parasite density dynamics assessed by qPCR [ Time Frame: up to 3 months after malaria sporozoite challenge ]
    To assess any differences in efficacy estimates with ID versus DVI challenge in individuals receiving R21/MM



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adults aged 18 to 45 years
  • 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 the duration of study for female participants. For those with no contraception, they will be referred for contraception at the relevant health facility. 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 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)
  • Provide written informed consent
  • Plan to remain resident in the study area for 1 year following first dose of vaccination

Exclusion Criteria:

  • Clinically significant congenital abnormalities as judged by the study clinicians
  • 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 disease
  • 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
  • Haemoglobin less than 11.3 g/dl for men and less than 10g/dl for in women, where judged to be clinically significant in the opinion of the investigator.
  • 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)
  • Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
  • Women only; pregnancy, or an intention to become pregnant a day before challenge i.e. at C-1
  • 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
  • Confirmed parasite positive by PCR a day before challenge i.e. at C-1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03947190


Contacts
Layout table for location contacts
Contact: Rachel Roberts +44 (0)1865 611418 vaccinetrials@ndm.ox.ac.uk

Sponsors and Collaborators
University of Oxford
Kenya Medical Research Institute
The European & Developing Countries Clinical Trials Partnership (EDCTP), European Union
Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03947190    
Other Study ID Numbers: VAC074
First Posted: May 13, 2019    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: May 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases