Clinical trial NCT04009096: VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines
Official title: A Phase IIa Challenge Study to Assess Efficacy of the Plasmodium Vivax Malaria Vaccine Candidates ChAd63 PvDBP and MVA PvDBP in Healthy Adults Living in the UK
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria, Vivax
Keywords: PvDBP
efficacy
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is an open label, Phase IIa, controlled human malaria infection (CHMI) study aimed to assess whether the new vivax malaria vaccines ChAd63 PvDBP and MVA PvDBP can protect against malaria infection.

The participants will receive one or two doses of ChAd63 PvDBP followed by one dose of MVA PvDBP 8 weeks later.

Approximately 4 weeks after the second vacccination, the volunteers will be challenged (deliberately infected) with malaria by intravenous injection blood-stage

Detailed description: Volunteers will be recruited and vaccinated at the CCVTM, Oxford.

There will be two groups vaccinated in the trial, with an optional third group included if fewer than 6 volunteers complete group 2. Up to 19 volunteers will be included in total. These will be compared to a matched number of infectivity controls, receiving no vaccination, who will be recruited as part of a separate study (VAC069 - NCT03797989).

Eligibility criteria: Inclusion Criteria:

* Healthy adult aged 18 to 45 years.
* Red blood cells positive for the Duffy antigen/chemokine receptor (DARC).
* Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PD).
* 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 permanently refrain from blood donation
* Written informed consent to participate in the trial.
* Reachable (24/7) by mobile phone during the period between CHMI and completion of all antimalarial treatment.
* Willing to take a curative anti-malarial regimen following CHMI.
* Willing to reside in Oxford for the duration of the study, until antimalarials have been completed.
* Answer all questions on the informed consent quiz correctly.

  * Female volunteers are required to use an effective form of contraception during the course of the study as malaria challenge could pose a serious risk to both maternal health and the unborn foetus.

Exclusion Criteria:

* History of clinical malaria (any species).
* Travel to a clearly malaria endemic locality during the study period or within the preceding six months.
* Current or planned treatment with long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
* Chronic use of antibiotics with antimalarial effects (e.g. tetracyclines for dermatologic patients, trimethoprim-sulfamethoxazole for recurrent urinary tract infections, etc.).
* Weight less than 50kg, as measured at the screening visit.
* Receipt of immunoglobulins within the three months prior to planned administration of the vaccine candidate.
* Receipt of blood products (e.g., blood transfusion) at any time in the past.
* Peripheral venous access unlikely to allow twice daily blood testing (as determined by the Investigator).
* Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
* Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days preceding or following each study vaccination, with the exception of licensed COVID-19 vaccines, which should not be received within 14 days before or 7 days after any study vaccination.
* Planned receipt of a COVID-19 vaccine between 2 weeks before the day of CHMI until completion of antimalarial treatment
* Concurrent involvement in another clinical trial or planned involvement during the study period.
* Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data or the P. vivax parasite as assessed by the Investigator.
* History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
* 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).
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine e.g. egg products, Kathon, aminoglycosides.
* History of allergic disease or reactions likely to be exacerbated by malaria infection.
* History of clinically significant contact dermatitis.
* Any history of anaphylaxis in reaction to vaccinations.
* 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.
* Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia.
* Family history of congenital QT prolongation or sudden death.
* Contraindications to the use of both of the proposed anti-malarial medications; Riamet Malarone.
* 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 25 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 or (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).
* Positive family history in both 1st AND 2nd degree relatives \< 50 years old for cardiac disease.
* Volunteers unable to be closely followed for social, geographic or psychological reasons.
* Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027.
* Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
* Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate.

Primary outcomes:
measure: Efficacy of the ChAd63 and MVA PvDBP Vaccines, Administered in a Heterologous Prime-boost Regimen, Assessed by a Reduced Parasite Multiplication Rate in Vaccinated Subjects
timeFrame: 3 months post CHMI
Secondary outcomes:
measure: Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers
timeFrame: Within 28 days following each vaccination. Vaccinations occurred at 0 and 2 months in Groups 1 and 3 (ChAd63, MVA PvDBP); and at 0, 17 and 19 months in Group 2 (ChAd63, ChAd63, MVA PvDBP).
measure: The Humoral Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen
timeFrame: 14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3; and at 19 months in Group 2.
measure: The Cellular Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen
timeFrame: 14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3 ; and at 19 months in Group 2.
measure: Immunological Readouts for Association With a Reduced Parasite Multiplication Rate
timeFrame: 3 months post CHMI
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Centre for Clinical Vaccinology & Tropical Medicine
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Angela M Minassian, MBBS MA DPhil MRCP FRCPath
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hou MM, Barrett JR, Themistocleous Y, Rawlinson TA, Diouf A, Martinez FJ, Nielsen CM, Lias AM, King LDW, Edwards NJ, Greenwood NM, Kingham L, Poulton ID, Khozoee B, Goh C, Mac Lochlainn DJ, Salkeld J, Guilotte-Blisnick M, Huon C, Mohring F, Reimer JM, Chauhan VS, Mukherjee P, Biswas S, Taylor IJ, Lawrie AM, Cho JS, Nugent FL, Long CA, Moon RW, Miura K, Silk SE, Chitnis CE, Minassian AM, Draper SJ. Impact of a blood-stage vaccine on Plasmodium vivax malaria. medRxiv [Preprint]. 2022 May 30:2022.05.27.22275375. doi: 10.1101/2022.05.27.22275375.