An Efficacy Study of IV Boosting With ChAd63/MVA ME-TRAP

NCT03707353 | Completed Phase 1 DMC

• 1 other identifier: VAC066
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief Summary

Plasmodium falciparum Malaria remains a major global health problem with approximately 200 million cases and 500,000 deaths worldwide annually, mostly in African infants. Current malarial control strategies are threatened by emergence of parasite resistance to drug treatment and resistance of the mosquito vector to certain insecticides. A deployable malaria vaccine is therefore a key strategy for reducing malaria mortality and progressing towards global eradication, but those in clinical trials are currently someway short of WHO targets. ChAd63 ME-TRAP and MVA ME-TRAP are leading candidate vaccines being developed by Adrian Hill's group at the University of Oxford, and collaborators. Since 2007, testing of these vaccines intramuscularly in over 900 volunteers has shown them to be safe, well tolerated and capable of delivering partial efficacy against malaria infection. This study will be the first time studying the efficacy of giving a boosting dose of the vaccines intravenously in what the investigators call a "prime-target" strategy. It follows very encouraging pre-clinical work showing this route can target desirable immune responses to the liver to fight a crucial stage of malaria infection. An ongoing recent phase I study is dose escalating both these vaccines intravenously as a single dose prior to commencing this trial where intramuscular and intravenous doses will be combined for the first time. The investigators will initially recruit 46 healthy UK adult volunteers who will be enrolled into 4 vaccination arms (10 volunteers each) and an unvaccinated control group (6 volunteers) who will undergo a controlled human malaria infection (CHMI). These are standardised, carefully supervised infection experiments used internationally to assess vaccine efficacy. As this is the first time giving intramuscular and intravenous doses of these vaccines in a combined schedule, the investigators will closely profile the safety and immune response during the vaccination follow-up. All trial activity will take place in Oxford.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Efficacy and safety of intramuscular vaccination followed by intravenous boosting with ChAd63 and MVA encoding ME-TRAP, in healthy malaria-naïve volunteers, assessed by frequency of adverse events

  Occurrence of solicited and unsolicited local and systemic adverse events

  Solicited and Unsolicited AEs will be collected for 28 days. SAEs will be collected from enrolment until the end of the follow-up period (16 weeks following completion of the prime target regimen)

Secondary Outcomes (1)

• To assess cell-mediated immunogenicity generated in malaria naïve individuals of vaccination schedules incorporating intramuscular prime dose(s) followed by intravenous booster with ChAd63 and MVA encoding ME-TRAP.

  Up to 11-13 months from initial vaccination

Study Arms (7)

Group 1

EXPERIMENTAL

Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, then MVA ME-TRAP vaccination intramuscularly followed by ChAd63 ME-TRAP vaccination intravenously.

Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination

Group 2

EXPERIMENTAL

Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, then MVA ME-TRAP vaccination intramuscularly followed by MVA ME-TRAP vaccination intravenously.

Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination

Group 3

EXPERIMENTAL

Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, followed by ChAd63 ME-TRAP vaccination intravenously.

Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination

Group 4

EXPERIMENTAL

Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, followed by MVA ME-TRAP vaccination intravenously. 4 weeks after the last vaccine dose, all vaccinated volunteers will undergo malaria challenge by mosquito bite.

Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination

Group 5

NO INTERVENTION

6 Volunteers will receive no vaccinations but will undergo malaria challenge infection by mosquito bite at the same time as groups 1-4.

Group 6

NO INTERVENTION

6 Volunteers will be used as infectivity controls if any volunteers from Groups 1-4 are rechallenged 5 - 7 months after the initial CHMI.

Group A

EXPERIMENTAL

Volunteers will receive ChAd63 ME-TRAP vaccination intramuscularly, then MVA ME-TRAP vaccination intramuscularly followed by MVA ME-TRAP vaccination intravenously.

Biological: ChAd63 ME-TRAP and MVA ME-TRAP vaccination

Interventions

ChAd63 ME-TRAP and MVA ME-TRAP vaccination BIOLOGICAL

vaccination with ChAd63 ME-TRAP 5x10\^10 vp (intramuscularly and intravenously) vaccination with MVA METRAP 2x10\^8 pfu (intramuscularly) and MVA METRAP 2x10\^7 pfu (intravenously) Group 5 will be challenged with malaria by mosquito bite.

Group 1; Group 2; Group 3; Group 4; Group A

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
• For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent to participate in the trial.
• 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.
• Reachable (24/7) by mobile phone during the period between CHMI and completion of antimalarial treatment.
• Willingness to provide a named person who may be contacted in the event it is not possible to locate the volunteer following CHMI
• Willingness to take a curative anti-malaria regimen following CHMI.
• For volunteers not living in Oxford: 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
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
• 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.
• Pregnancy, lactation or 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 that may affect participation in the study.
• 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 standard UK units every week.
• Suspected or known injecting drug abuse in the 5 years preceding enrolment.
• Hepatitis B surface antigen (HBsAg) detected in serum.
• Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study).

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (4)

NIHR Clinical Research Facility, Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

CCVTM, University of Oxford

Oxford, OX3 7LE, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Southampton National Institute for Health Research

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Study Officials

• Adrian V Hill, DPhill FRCP

  Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 16, 2018
• Study Start: October 30, 2018
• Primary Completion: June 10, 2019
• Study Completion: June 10, 2019
• Last Updated: September 26, 2019

Record last verified: 2019-07

Locations

GB (4)