VAC 072-An Efficacy Study of R21/MM in Different Dose Schedules

NCT ID: NCT03970993

Last Updated: 2021-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-17

Study Completion Date

2021-08-24

Brief Summary

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An open label, partially blinded clinical trial in which healthy volunteers will be administered experimental malaria vaccines. There will be seven experimental groups of volunteers, of which five receive vaccination with the novel malaria vaccine candidate, R21, in combination with the vaccine adjuvant, Matrix M.

The study will assess the safety \& immune responses to vaccination, and the efficacy of the vaccine.

Detailed Description

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Arms 1a \& 1b receive vaccines at 3 vaccinations at 4 week intervals and a booster vaccination approximately 12 months after the first vaccination.

Arms 2a \& 2b receive 3 vaccinations at 0, 4 and 24 weeks. The protected volunteers in 2a from the first malaria challenge, VAC072A, will receive a booster vaccination 28 days before the rechallenge, VAC072B.

Arms 3a and 3b receive 3 vaccinations at 0, 4 and 8 weeks. The protected volunteers in 3a from the first malaria challenge, VAC072A, will receive a booster vaccination 28 days before the rechallenge, VAC072B.

Arms 4a and 4b will receive 3 vaccinations at 0, 4 and 24 weeks. The third dose is fractional. Volunteers then have the option to be challenged 28 days after final vaccination.

Group 5 will receive 3 vaccinations at 0, 4 and 24 weeks. The third dose is fractional. Volunteers then have the option to be challenged 28 days after final vaccination.

Groups 6 \& 7 are control groups and will receive controlled human malaria infection (CHMI)

Healthy volunteers will be recruited in England across four research sites in Oxford, London, and Southampton.

Conditions

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Malaria

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group 1a

Volunteers will receive 3 doses of 10μg R21/50μg Matrix-M 4 weeks apart and an optional booster vaccination 12 months after the third dose

Group Type EXPERIMENTAL

R21 Matrix-M vaccination

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly

R21 Matrix-M vaccination booster

Intervention Type BIOLOGICAL

Optional R21 Matrix-M vaccination booster following a three dose vaccination schedule

Group 2a

Volunteers will receive 3 doses of 10μg R21/50μg Matrix-M at 0, 4 and 24 weeks, followed by CHMI by sporozoite challenge (mosquito bite) 4 weeks later. If protected from malaria, volunteers will receive an optional booster vaccination 28 days prior to malaria rechallenge

Group Type EXPERIMENTAL

R21 Matrix-M vaccination and CHMI

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly. Volunteers then have the option to be challenged with malaria by mosquito bite

R21 Matrix-M vaccination booster

Intervention Type BIOLOGICAL

Optional R21 Matrix-M vaccination booster following a three dose vaccination schedule

Group 3a

Volunteers will receive 3 doses of 10μg R21/50μg Matrix-M 4 weeks apart, followed by CHMI by sporozoite challenge (mosquito bite) 4 weeks later. If protected from malaria, volunteers will receive an optional booster vaccination 28 days prior to malaria rechallenge

Group Type EXPERIMENTAL

R21 Matrix-M vaccination and CHMI

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly. Volunteers then have the option to be challenged with malaria by mosquito bite

R21 Matrix-M vaccination booster

Intervention Type BIOLOGICAL

Optional R21 Matrix-M vaccination booster following a three dose vaccination schedule

Group 4a

Volunteers will receive 2 doses of 50μg R21/50μg Matrix-M 4 weeks apart and a 3rd fractional dose of 10μg R21/50μg Matrix-M at 24 weeks. This is followed by optional CHMI by sporozoite challenge (mosquito bite) 4 weeks later

Group Type EXPERIMENTAL

R21 Matrix-M vaccination and CHMI

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly. Volunteers then have the option to be challenged with malaria by mosquito bite

Group 5

Volunteers will receive 2 doses of 10μg R21/50μg Matrix-M 4 weeks apart and a 3rd fractional dose of 2μg R21/50μg Matrix-M at 24 weeks. This is followed by optional CHMI by sporozoite challenge (mosquito bite) 4 weeks later

Group Type EXPERIMENTAL

R21 Matrix-M vaccination and CHMI

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly. Volunteers then have the option to be challenged with malaria by mosquito bite

Group 6

They are infectivity control volunteers for the sporozoite challenge procedures: these volunteers are not vaccinated.

Group Type NO_INTERVENTION

No interventions assigned to this group

Group 7

They are infectivity control volunteers for the sporozoite challenge procedures: these volunteers are not vaccinated.

Group Type NO_INTERVENTION

No interventions assigned to this group

Group 1b

Volunteers will receive 3 doses of 10μg R21/50μg Matrix-M, 4 weeks apart followed by an optional vaccination booster 12 months after the third dose.

Group Type EXPERIMENTAL

R21 Matrix-M vaccination

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly

R21 Matrix-M vaccination booster

Intervention Type BIOLOGICAL

Optional R21 Matrix-M vaccination booster following a three dose vaccination schedule

Group 2b

Volunteers will receive 3 doses of 10μg R21/50μg Matrix-M at 0, 4 and 24 weeks.

Group Type EXPERIMENTAL

R21 Matrix-M vaccination

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly

Group 3b

Volunteers will receive 3 doses of 10μg R21/50μg Matrix-M 4 weeks apart.

Group Type EXPERIMENTAL

R21 Matrix-M vaccination

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly

Group 4b

Volunteers will receive 2 doses of 50μg R21/50μg Matrix-M 4 weeks apart and a 3rd fractional dose of 10μg R21/50μg Matrix-M at 24 weeks.

Group Type EXPERIMENTAL

R21 Matrix-M vaccination

Intervention Type BIOLOGICAL

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly

Interventions

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R21 Matrix-M vaccination

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly

Intervention Type BIOLOGICAL

R21 Matrix-M vaccination and CHMI

Three dose vaccination of 2μg, 10μg or 50μg of R21 and 50ug Matrix-M delivered intramuscularly. Volunteers then have the option to be challenged with malaria by mosquito bite

Intervention Type BIOLOGICAL

R21 Matrix-M vaccination booster

Optional R21 Matrix-M vaccination booster following a three dose vaccination schedule

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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.
* Agree to refrain from blood donation 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 the malaria challenge follow-up site (CCVTM, 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.\*

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
* 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.
* Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data as assessed by the investigator.
* 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) 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 and existing contraindication to the use of Malarone.\*
* History of cardiac arrhythmia, including clinically relevant bradycardia and existing contraindication to the use of Malarone.\*
* Clinically significant disturbances of electrolyte balance, eg, hypokalaemia or hypomagnesaemia
* Family history of congenital QT prolongation or sudden death and existing contraindication to the use of Malarone.\*
* Contraindications to the use of both Riamet and 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.
* 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).
* 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 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.

* Not applicable for volunteers who do not undergo CHMI (Groups 1, 4 and 5)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adrian V Hill, DPhill FRCP

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

CCVTM, University of Oxford, Churchill Hospital

Oxford, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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VAC072

Identifier Type: -

Identifier Source: org_study_id