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

Malaria,Falciparum Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03947190
• Other study ID #: VAC074
• Status: Recruiting
• Phase: Phase 2
• Start date: August 31, 2022
• Est. completion date: April 2023

Study information

• Verified date: September 2022
• Source: University of Oxford
• Contact: Rachel Roberts
• Phone: +44 (0)1865 611418
• Email: vaccinetrials[@]ndm.ox.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Malaria,Falciparum

Intervention

Biological:
• R21/Matrix-M
R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant.
• 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.
• intradermal injection (ID) or direct venous injection (DVI) of PfSPZ Challenge
PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites.

Locations

Country	Name	City	State
Kenya	KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research - Coast	Kilifi

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	European and Developing Countries Clinical Trials Partnership (EDCTP), Kenya Medical Research Institute

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	To measure cellular immunogenicity assessed by ELISPOT	Assessing cellular immunogenicity by ELISPOT to enumerate IFN-? producing T cells	from vaccination day up to 90 days after malaria sporozoite challenge
Secondary	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
Secondary	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