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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Malaria,Falciparum
• Intervention / Treatment: Biological: R21/Matrix-M; Biological: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge; Biological: ChAd63/MVA ME-TRAP

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.

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Kenya
  • Kilifi, Kenya, PO Box 230, 80108
    • Recruiting
    • KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast
    • Contact: Mainga Hamaluba; Email: MHamaluba@kemri-wellcome.org
    • Principal Investigator: Mainga Hamaluba
    • Principal Investigator: Melissa Kapulu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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: intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge; PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.; 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of solicited local and systemic reactogenicity signs and symptoms, and unsolicited adverse events	Assessing the safety and reactogenicity of adjuvanted R21/MM and heterologous prime- boost regime of ChAd63-MVA ME-TRAP in healthy adult volunteers	Solicited AEs are collected for 7 days post vaccination and unsolicited AEs for 28 days post vaccination
Occurrence of P. falciparum parasitemia assessed by PCR, and parasite density dynamics assessed by PCR, against malaria sporozoite challenge	To assess the safety of intradermal sporozoite infection dose in semi-immune healthy adult volunteers	up to 3 months after malaria sporozoite challenge
Occurrence of P. falciparum parasitemia, assessed by qPCR	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	from vaccination day up to 90 days after malaria sporozoite challenge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure cellular immunogenicity assessed by ELISPOT	Assessing cellular immunogenicity by ELISPOT to enumerate IFN-ƴ producing T cells	from vaccination day up to 90 days after malaria sporozoite challenge
To measure humoral immunogenicity assessed by ELISA	Assessing humoral immunogenicity by ELISA to quantify antibodies to the vaccine components CS, NANP, TRAP and HBsAb.	from vaccination day up to 90 days after malaria sporozoite challenge
Parasite density dynamics assessed by qPCR	To assess any differences in efficacy estimates with ID versus DVI challenge in individuals receiving R21/MM	up to 3 months after malaria sporozoite challenge

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: European and Developing Countries Clinical Trials Partnership (EDCTP); Kenya Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 14, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum
• Other Study ID Numbers: VAC074

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No