A Safety and Efficacy Study of R21 +/- ChAd63/MVA ME-TRAP

NCT02905019 | Completed Phase 1 DMC

• 1 other identifier: VAC065
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess the safety and efficacy of adjuvanted R21 alone and in combination with a viral-vectored vaccine regimen (constituting adjuvanted R21 + ChAd63 and MVA encoding ME-TRAP) against malaria sporozoite challenge in healthy malaria-naive volunteers. Healthy adult volunteers will be recruited in London, Oxford and Southampton. All vaccinations will be administered intramuscularly. The study involves having either two, three or five vaccinations and then undergoing challenge infection with malaria, or receiving no vaccinations then undergoing challenge infection with malaria.

Conditions

Malaria

Outcome Measures

Primary Outcomes (2)

• Efficacy of adjuvanted R21 at two different doses and adjuvanted R21 + ChAd63 and MVA encoding ME-TRAP in healthy malaria-naïve volunteers as assessed by number of completely protected individuals.

  Use statistical analysis to compare number of completely protected individuals (those who do not, by Day 21 following sporozoite challenge, develop blood stage infection measured by occurrence of P. falciparum parasitemia, assessed by blood slide) in the vaccine groups compared to the controls.

  6 months

• Safety of adjuvanted R21 at two different doses and adjuvanted R21 + ChAd63 and MVA encoding ME-TRAP in healthy malaria-naïve volunteers as assessed by frequency of adverse events.

  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.

  6 months

Secondary Outcomes (5)

• Humoral immunogenicity generated in malaria naïve individuals with adjuvanted R21 at two different doses

  6 months

• Cell-mediated immunogenicity generated in malaria naïve individuals with ChAd63 and MVA encoding ME-TRAP

  6 months

• Efficacy measured as time to P. falciparum parasitemia assessed by PCR against malaria sporozoite challenge, in healthy malaria-naïve volunteers.

  6 months

• Efficacy measured as time to P. falciparum parasitemia assessed by blood slide against malaria sporozoite challenge, in healthy malaria-naïve volunteers.

  6 months

• Efficacy measured as time to P. falciparum parasitemia assessed by parasite density dynamics assessed by PCR against malaria sporozoite challenge, in healthy malaria-naïve volunteers.

  6 months

Other Outcomes (1)

• Long term protective efficacy of adjuvanted R21 at two different doses and adjuvanted R21 + ChAd63 and MVA encoding ME-TRAP

  12 months

Study Arms (9)

Standard Dose x3 (Group 1)

ACTIVE COMPARATOR

R21 with Matrix-M1. Three vaccinations with 10 µg R21/ 50 µg Matrix-M1 on days 0, 28 and 56.

Biological: R21 with Matrix-M1

High Dose (Group 2)

ACTIVE COMPARATOR

R21 with Matrix-M1. Two vaccinations with 50µg R21/50µg Matrix-M1 on days 0 and 28 and one vaccination with 10 µg R21/ 50 µg Matrix M1 on day 56.

Biological: R21 with Matrix-M1

Combination (Group 3)

ACTIVE COMPARATOR

R21 with Matrix-M1, ChAd63 ME-TRAP and MVA ME-TRAP. Three vaccinations with 10 µg R21/ 50 µg Matrix-M1 on days 0 , 28 and 56. Plus one vaccination with ChAd63 ME-TRAP on day 7 and one vaccination with MVA ME-TRAP on day 63.

Biological: R21 with Matrix-M1; Biological: ChAd63 ME-TRAP; Biological: MVA ME-TRAP

Control Group 4a

NO INTERVENTION

These volunteers will not be vaccinated and will serve as infectivity controls when groups 1-3 undergo challenge.

Control Group 4b

NO INTERVENTION

These volunteers will not be vaccinated and will serve as infectivity controls when group 5-7 and sterilely protected volunteers from groups 1-3 undergo challenge.

Control Group 4c

NO INTERVENTION

These volunteers will not be vaccinated and will serve as infectivity controls if any volunteers from groups 5 and 7 are rechallenged.

Fractional Dose (Group 5)

ACTIVE COMPARATOR

R21 with Matrix-M1. Two vaccinations with 10 µg R21/ 50 µg Matrix-M1 on days 0 and 28 and one vaccination with 2µg R21/ 50 µg Matrix-M1 on day 56.

Biological: R21 with Matrix-M1

Long-term Efficacy (Group 6)

NO INTERVENTION

Volunteers in this group have received vaccinations in a different malaria vaccine trial. These volunteers will not receive any vaccinations in this trial, but will undergo controlled human malaria infection as part of this study.

Standard Dose x2 (Group 7)

ACTIVE COMPARATOR

R21 with Matrix-M1. Two vaccinations with 10 µg R21/ 50 µg Matrix-M1 on days 0 and 28.

Biological: R21 with Matrix-M1

Interventions

R21 with Matrix-M1 BIOLOGICAL

Vaccine

Combination (Group 3); Fractional Dose (Group 5); High Dose (Group 2); Standard Dose x2 (Group 7); Standard Dose x3 (Group 1)

ChAd63 ME-TRAP BIOLOGICAL

Vaccine

Combination (Group 3)

MVA ME-TRAP BIOLOGICAL

Vaccine

Combination (Group 3)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18 to 45 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.
• Women only: Must practice continuous effective contraception\* for the duration of the study.
• Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
• Written informed consent to participate in the trial.
• Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment.
• Willingness to take a curative anti-malaria regimen following CHMI.
• For volunteers not living close to their designated malaria challenge follow-up site (Oxford or Southampton): agreement to stay in a hotel room close to the trial centre during a part of the study (from at least day 6.5 post mosquito bite until anti-malarial treatment is completed).
• Answer all questions on the informed consent quiz correctly.

You may not qualify if:

• History of clinical malaria (any species).
• Travel to a clearly malaria endemic locality during the study period or within the preceding six months
• Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
• For Group 3 volunteers only: prior receipt of a non-malaria MVA or non-malaria adenovirus vectored experimental vaccine
• 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).
• Use of immunoglobulins or blood products within 3 months prior to enrolment.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon) or malaria infection.
• Any history of anaphylaxis post vaccination.
• History of clinically significant contact dermatitis.
• History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
• Pregnancy, lactation or intention to become pregnant during the study.
• Use of medications known to cause prolongation of the QT interval and existing contraindication to the use of Malarone
• Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone
• Any clinical condition known to prolong the QT interval

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (3)

NIHR Wellcome Trust Clinical Research Facility, Hammersmith Hospital

London, United Kingdom

Location

CCVTM, University of Oxford,

Oxford, OX3 7LE, United Kingdom

Location

Southampton National Institute for Health Research

Southampton, United Kingdom

Location

Related Publications (2)

• Venkatraman N, Silman D, Bellamy D, Stockdale L, Bowyer G, Edwards NJ, Griffiths O, Lopez FR, Powlson J, Mair C, Folegatti PM, Datoo MS, Morter R, Minassian AM, Poulton I, Collins KA, Brod F, Angell-Manning P, Berrie E, Brendish N, Glenn G, Fries L, Baum J, Blagborough AM, Roberts R, Lawrie AM, Angus B, Lewis DJM, Faust SN, Ewer KJ, Hill AVS. R21 in Matrix-M adjuvant in UK malaria-naive adult men and non-pregnant women aged 18-45 years: an open-label, partially blinded, phase 1-2a controlled human malaria infection study. Lancet Microbe. 2025 Mar;6(3):100867. doi: 10.1016/S2666-5247(24)00083-1. Epub 2025 Jan 10.

  PMID: 39805301 DERIVED

• Ssemaganda A, Giddam AK, Zaman M, Skwarczynski M, Toth I, Stanisic DI, Good MF. Induction of Plasmodium-Specific Immune Responses Using Liposome-Based Vaccines. Front Immunol. 2019 Feb 1;10:135. doi: 10.3389/fimmu.2019.00135. eCollection 2019.

  PMID: 30774635 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Matrix-M

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Adrian V Hill, DPhil FRCP

  Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hosptal, Oxford, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: September 19, 2016
• Study Start: August 1, 2016
• Primary Completion: December 21, 2017
• Study Completion: December 21, 2017
• Last Updated: June 13, 2018

Record last verified: 2017-08

Locations

GB (3)