A Safety and Efficacy Study of ChAd63/MVA METRAP + RTS,S

NCT01883609 | Completed Phase 1

• 2 other identifiers: VAC0552013-000393-30
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

This is a clinical trial in which healthy volunteers will be administered experimental malaria vaccines. One group of volunteers will receive vaccination with the leading malaria vaccine candidate, RTS,S/AS01. This vaccine schedule will consist of 3 doses of RTS,S/AS01 with an interval of 4 weeks between doses (Doses given at 0,4 and 8 week timepoints). Another group will receive a vaccination schedule composed of the same dosage and timing regimen of RTS,S, but they will also receive vaccination with ChAd63 ME-TRAP, 2 weeks after the first RTS,S followed 8 weeks later by vaccination with MVA ME-TRAP (2 and 10 week timepoints). The study will assess the safety of the vaccinations, and the immune responses to vaccination. Immune responses are measured by tests on blood samples. Volunteers will be infected with malaria by mosquito bites, 12 weeks after the first vaccination. In addition, a group of volunteers not receiving vaccines will also be infected with malaria by the same method. These infection experiments will be used to assess vaccine efficacy: how well the vaccines act to prevent malaria disease. A further single volunteer may also be infected with malaria; this volunteer participated in a previous trial where they received vaccines and was completely protected against malaria disease after infection by mosquito bite. The RTS,S/AS01 vaccine is a protein (RTS,S) mixed with an adjuvant (AS01). The ChAd63 ME-TRAP and MVA ME-TRAP vaccines are called viral vectored vaccines. They are made from viruses which are modified so that they can not multiply. The viruses have extra DNA in them so that after injection, the body makes malaria proteins (but malaria does not develop), so that the immune system builds a response to malaria without having been infected by it. Healthy volunteers will be recruited in England at three research sites: in Oxford, London and Southampton.

Conditions

Plasmodium Falciparum Malaria

Keywords

Plasmodium Falciparum; Malaria; Vaccine; Plasmodium; Falciparum

Outcome Measures

Primary Outcomes (2)

• To assess the efficacy of a combination immunization regimen with ChAd63/MVA ME-TRAP and RTS,S/AS01B, and of RTS,S/AS01B alone, against malaria sporozoite challenge, in healthy malaria-naïve volunteers.

  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).

  12 months

• To assess the safety of a combination immunization regimen with ChAd63/MVA ME-TRAP and RTS,S/AS01B, and of RTS,S/AS01B alone, in healthy malaria-naïve volunteers.

  Occurrence of solicited and unsolicited adverse events will be monitored at each clinic visit (from diary cards, clinical review, clinical examination (including observations) and laboratory results).

  12 months

Secondary Outcomes (2)

• To assess immunogenicity generated in malaria naïve individuals of a malaria vaccine schedule containing RTS,S/AS01B and ChAd63/MVA ME-TRAP, and of RTS,S/AS01B alone.

  12 months

• To assess the efficacy of a combination immunization regimen with ChAd63/MVA ME-TRAP and RTS,S/AS01B, and of RTS,S/AS01B alone, against malaria sporozoite challenge, in healthy malaria-naïve volunteers.

  12 months

Other Outcomes (1)

• To assess the long term protective efficacy of a combination vaccine schedule of RTS,S/AS01B and ChAd63-MVA ME-TRAP by re-challenge of volunteers exhibiting sterile protection.

  12 months

Study Arms (4)

Group 1

ACTIVE COMPARATOR

Group 1 receive combination vaccination strategy: RTS,S/AS01B at weeks 0, ChAd63 ME-TRAP at week 2, RTS,S/AS01B at weeks 4 and 8, then MVA ME-TRAP at week 10 followed by sporozoite challenge (mosquito bite) at week 12.

Biological: RTS,S/AS01B; Biological: ChAd63 ME-TRAP; Biological: MVA ME-TRAP

Group 2

ACTIVE COMPARATOR

Group 2 receive three vaccinations (RTS,S/AS01B) at weeks 0, 4 and 8 followed by sporozoite challenge (mosquito bite) at week 12.

Biological: RTS,S/AS01B

Group 3

NO INTERVENTION

Groups 3 is an infectivity-control group for the sporozoite challenge procedures: these volunteers will not be vaccinated. Group 3 will undergo sporozoite challenge at the same time as Group 1 and 2 volunteers (week 12).

Group 4

NO INTERVENTION

Group 4 is an infectivity-control group for the sporozoite challenge procedures: these volunteers will not be vaccinated. Group 4 volunteers will be used as infectivity controls if any volunteers from groups 1 and 2 are rechallenged 5 - 7 months after the initial CHMI. CHMI may be administered in two separate cohorts if necessary due to limitations on volunteer availability.

Interventions

RTS,S/AS01B BIOLOGICAL

Each RTS,S/AS01B dose will be given intramuscularly, and will contain 50mcg of RTS,S and standard adult dose of AS01

Group 1; Group 2

ChAd63 ME-TRAP BIOLOGICAL

ChAd63 ME-TRAP will be given intramuscularly at a dose of 5 x 1010 vp

Group 1

MVA ME-TRAP BIOLOGICAL

MVA ME-TRAP will be given intramuscularly at a dose of 2 x 108 pfu

Group 1

Eligibility Criteria

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

You may qualify if:

• The volunteer must satisfy all the following criteria to be eligible for the study:
• 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 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:

• The volunteer may not enter the study if any of the following apply:
• History of clinical malaria (any species).
• Travel to a malaria endemic region during the study period or within the preceding six months with significant risk of malaria exposure.
• 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.
• 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 (4)

Wellcome Trust CRF, Southampton General Hospital, University of Southampton

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Infection and Immunity Section, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine

London, SW7 2AZ, United Kingdom

Location

Hammersmith Hospital, Imperial College NHS Trust

London, W12 0HS, United Kingdom

Location

Related Publications (2)

• Li K, Dodds M, Spreng RL, Abraha M, Huntwork RHC, Dahora LC, Nyanhete T, Dutta S, Wille-Reece U, Jongert E, Ewer KJ, Hill AVS, Jin C, Hill J, Pollard AJ, Munir Alam S, Tomaras GD, Dennison SM. A tool for evaluating heterogeneity in avidity of polyclonal antibodies. Front Immunol. 2023 Feb 16;14:1049673. doi: 10.3389/fimmu.2023.1049673. eCollection 2023.

  PMID: 36875126 DERIVED

• Rampling T, Ewer KJ, Bowyer G, Bliss CM, Edwards NJ, Wright D, Payne RO, Venkatraman N, de Barra E, Snudden CM, Poulton ID, de Graaf H, Sukhtankar P, Roberts R, Ivinson K, Weltzin R, Rajkumar BY, Wille-Reece U, Lee CK, Ockenhouse CF, Sinden RE, Gerry S, Lawrie AM, Vekemans J, Morelle D, Lievens M, Ballou RW, Cooke GS, Faust SN, Gilbert S, Hill AV. Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP. J Infect Dis. 2016 Sep 1;214(5):772-81. doi: 10.1093/infdis/jiw244. Epub 2016 Jun 15.

  PMID: 27307573 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

RTS,S-AS01B vaccine

Condition Hierarchy (Ancestors)

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

Study Officials

• Adrian V S Hill, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Saul N Faust

  University of Southampton

  PRINCIPAL INVESTIGATOR

• Graham S Cooke

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 13, 2013
• First Posted: June 21, 2013
• Study Start: September 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 1, 2014

Record last verified: 2014-09

Locations

GB (4)