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

NCT03970993 | Completed Phase 1 DMC

• 1 other identifier: VAC072
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Malaria

Keywords

Malaria challenge; Malaria vaccine

Outcome Measures

Primary Outcomes (2)

• The safety and tolerability of adjuvanted R21 using different immunisation schedules in healthy malaria naïve volunteers

  Occurrence of solicited and unsolicited local and systemic adverse events

  Solicited AEs will be collected for 7 days and Unsolicited AEs will be collected for 28 days. SAEs will be collected from enrolment until the end of the follow-up period

• The efficacy (prevention of occurrence of P. falciparum parasitemia) of adjuvanted R21 against malaria sporozoite challenge, in healthy malaria-naïve volunteers using two immunisation regimes

  Assessed by PCR of adjuvanted R21 in two different vaccination regimes

  Weeks 2 & 3 following malaria infection

Secondary Outcomes (4)

• To assess humoral immunogenicity generated in malaria-naïve individuals by adjuvanted R21 using different immunisation schedules in healthy malaria-naïve volunteers.

  Blood samples will be taken to assess immune responses at specified time points over the duration of the study

• To assess the safety and tolerability of adjuvanted R21 using different immunisation schedules in healthy malaria-naïve volunteers following booster vaccination

  Solicited AEs will be collected for 7 days and Unsolicited AEs will be collected for 28 days. SAEs will be collected from enrolment until the end of the follow-up period

• To assess the efficacy of adjuvanted R21 against malaria sporozoite challenge in healthy malaria-naïve volunteers following a booster vaccination.

  Week 2 following malaria infection

• To further assess the efficacy using different thresholds of adjuvanted R21 in two different vaccination regimes and compared to R21c against malaria sporozoite challenge, in healthy malaria-naïve volunteers.

  Weeks 2 & 3 following malaria infection

Other Outcomes (1)

• To evaluate further exploratory immunological end points in the vaccinees.

  Duration of the study

Study Arms (11)

Group 1a

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination; Biological: R21 Matrix-M vaccination booster

Group 2a

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination and CHMI; Biological: R21 Matrix-M vaccination booster

Group 3a

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination and CHMI; Biological: R21 Matrix-M vaccination booster

Group 4a

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination and CHMI

Group 5

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination and CHMI

Group 6

NO INTERVENTION

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

Group 7

NO INTERVENTION

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

Group 1b

EXPERIMENTAL

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.

Biological: R21 Matrix-M vaccination; Biological: R21 Matrix-M vaccination booster

Group 2b

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination

Group 3b

EXPERIMENTAL

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

Biological: R21 Matrix-M vaccination

Group 4b

EXPERIMENTAL

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.

Biological: R21 Matrix-M vaccination

Interventions

R21 Matrix-M vaccination BIOLOGICAL

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

Group 1a; Group 1b; Group 2b; Group 3b; Group 4b

R21 Matrix-M vaccination and CHMI 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 2a; Group 3a; Group 4a; Group 5

R21 Matrix-M vaccination booster BIOLOGICAL

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

Group 1a; Group 1b; Group 2a; Group 3a

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.
• 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.\*

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
• 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.\*

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (4)

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

CCVTM, University of Oxford, Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Malaria

Interventions

1-acetyl-1,2,3,3a,8,8a-hexahydro-8a-hydroxy-5-methoxypyrrolo(2,3-b)indole

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, United Kingdom

  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: May 29, 2019
• First Posted: June 3, 2019
• Study Start: June 17, 2019
• Primary Completion: August 24, 2021
• Study Completion: August 24, 2021
• Last Updated: October 13, 2021

Record last verified: 2021-10

Locations

GB (4)