NCT02252640

Brief Summary

The purpose of this study is to assess two types of new malaria vaccines in different combinations. The study will enable us to assess:

  1. 1.The ability of the vaccines to prevent malaria infection.
  2. 2.The safety of the vaccines in healthy participants.
  3. 3.The response of the human immune system to the vaccines.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2015

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 25, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 30, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

January 1, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
Last Updated

December 3, 2015

Status Verified

December 1, 2015

Enrollment Period

9 months

First QC Date

September 25, 2014

Last Update Submit

December 2, 2015

Conditions

Plasmodium Falciparum Malaria

Keywords

Plasmodium FalciparumMalariaVaccinePlasmodiumFalciparum

Outcome Measures

Primary Outcomes (2)

  • Efficacy of a combination immunization regimen with ChAd63/MVA ME-TRAP given concomitantly with RTS,S/AS01B against malaria sporozoite challenge.

    Use statistical analysis to compare number of completely protected individuals (those who do not, by Day 23 following sporozoite challenge, develop blood stage infection measured by occurrence of P. falciparum parasitemia, assessed by blood slide)

    6 months

  • Safety of a combination immunization regimen with ChAd63/MVA ME-TRAP given concomitantly with RTS,S/AS01B against malaria sporozoite challenge.

    Occurrence of solicited and unsolicited adverse events will be monitored. Solicited and unsolicited AE data will be collected at each clinic visit. It will be collected 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 (1)

  • Immunogenicity generated in malaria naïve individuals of two different dosing regimens of RTS,S/AS01B given concomitantly with ChAd63/MVA ME-TRAP, and of RTS,S/AS01B alone at either full standard dose or with a reduced third dose.

    6 months

Other Outcomes (1)

  • Long term protective efficacy of a combination immunization regimen with ChAd63/MVA ME-TRAP given concomitantly with RTS,S/AS01B

    12 months

Study Arms (6)

Group 1

ACTIVE COMPARATOR

Week 0: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01), Week 4: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01), Week 8: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01), Week 11: Controlled Human Malaria Infection (CHMI), Week 31-39: Repeat CHMI of sterilely protected volunteers.

Biological: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01)

Group 2

ACTIVE COMPARATOR

Week 0: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01), Week 4: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01), Week 8: RTS,S/AS01B (10mcg of RTS,S and 1/5 of the standard dose of AS01), Week 11: Controlled Human Malaria Infection (CHMI), Week 31-39: Repeat CHMI of sterilely protected volunteers.

Biological: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01)Biological: RTS,S/AS01B (10mcg of RTS,S and one fifth of the standard dose of AS01)

Group 3

ACTIVE COMPARATOR

Week 0: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01) \& ChAd63 ME-TRAP (5 x 10\^10 vp), Week 4: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01) \& MVA ME-TRAP (2 x 10\^8 pfu), Week 8: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01) \& MVA ME-TRAP (2 x 10\^8 pfu), Week 11: Controlled Human Malaria Infection (CHMI), Week 31-39: Repeat CHMI of sterilely protected volunteers.

Biological: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01)Biological: ChAd63 ME-TRAP (5 x 10^10 vp)Biological: MVA ME-TRAP (2 x 10^8 pfu)

Group 4

ACTIVE COMPARATOR

Week 0: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01) \& ChAd63 ME-TRAP (5 x 10\^10 vp), Week 4: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01) \& MVA ME-TRAP (2 x 10\^8 pfu), Week 8: RTS,S/AS01B (10mcg of RTS,S and 1/5 of the standard dose of AS01) \& MVA ME-TRAP (2 x 10\^8 pfu), Week 11: Controlled Human Malaria Infection (CHMI), Week 31-39: Repeat CHMI of sterilely protected volunteers.

Biological: RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01)Biological: RTS,S/AS01B (10mcg of RTS,S and one fifth of the standard dose of AS01)Biological: ChAd63 ME-TRAP (5 x 10^10 vp)Biological: MVA ME-TRAP (2 x 10^8 pfu)

Group 5

NO INTERVENTION

Week 11: Controlled Human Malaria Infection

Group 6

NO INTERVENTION

Week 31-39: Controlled Human Malaria Infection

Interventions

RTS,S/AS01B (50mcg of RTS,S and standard adult dose of AS01)BIOLOGICAL
Group 1Group 2Group 3Group 4
RTS,S/AS01B (10mcg of RTS,S and one fifth of the standard dose of AS01)BIOLOGICAL
Group 2Group 4
ChAd63 ME-TRAP (5 x 10^10 vp)BIOLOGICAL
Group 3Group 4
MVA ME-TRAP (2 x 10^8 pfu)BIOLOGICAL
Group 3Group 4

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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 Controlled Human Malaria Infection (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:

  • 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
  • History of cardiac arrhythmia, including clinically relevant bradycardia
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

NIHR WTCRF, University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Surrey Clinical Research Centre, University of Surrey

Guildford, Surrey, GU2 7XP, United Kingdom

Location

NIHR/Wellcome Trust Imperial CRF, Hammersmith Hospital, Imperial College NHS Trust

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Malaria, FalciparumMalaria

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Study Officials

  • Adrian VS Hill

    University of Oxford

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

September 25, 2014

First Posted

September 30, 2014

Study Start

January 1, 2015

Primary Completion

October 1, 2015

Study Completion

October 1, 2015

Last Updated

December 3, 2015

Record last verified: 2015-12

Locations

GB(4)