VAC063C: A Study to Assess Repeat Blood-stage P. Falciparum Infection

NCT03906474 | Completed DMC

• 1 other identifier: VAC063C
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clinical study to assess the safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as well as to evaluate any effect of prior exposure to a blood-stage controlled human malaria infection (CHMI) on the parasite multiplication rate. As a secondary objective, the immune response to primary, secondary and tertiary P. falciparum blood-stage infection, as well as gametocytaemia, will also be assessed.

Conditions

Malaria

Outcome Measures

Primary Outcomes (2)

• The safety of primary, secondary and tertiary blood-stage controlled human Plasmodium falciparum malaria infection of healthy malaria-naïve UK adults, as measured by (S)AE occurrences.

  3 months

• The effect of prior blood-stage CHMI on parasite multiplication rate following tertiary (Group 1) and secondary (Group 2) homologous CHMI in unvaccinated volunteers, compared to primary challenge in new malaria naïve controls (Group 3).

  The qPCR-derived parasite multiplication rate (PMR) will be the primary endpoint for the trial, and reporting of the endpoint for Groups 1-3 will constitute the primary analysis.

  3 months

Secondary Outcomes (2)

• P. falciparum specific immunogenicity following primary, secondary and tertiary P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses

  2 years

• Gametocytaemia following primary, secondary and tertiary P. falciparum blood-stage infection.

  2 years

Study Arms (3)

Group 1

EXPERIMENTAL

A third blood-stage controlled human P. falciparum malaria infection will be administered to individuals who have previously been exposed to two blood-stage challenges in the VAC063 trial. Group 1 will be challenged in parallel with Groups 2 (undergoing a second challenge) and 3 (malaria-naïve controls).

Biological: Blood-stage controlled human P. falciparum malaria infection

Group 2

EXPERIMENTAL

A second blood-stage controlled human P. falciparum malaria infection will be administered to individuals who have previously been exposed to one blood-stage challenge in the VAC063 trial. Group 2 will be challenged in parallel with Groups 1 (undergoing a third challenge) and 3 (malaria-naïve controls).

Biological: Blood-stage controlled human P. falciparum malaria infection

Group 3

EXPERIMENTAL

Malaria-naïve controls will receive a primary blood-stage controlled human P. falciparum malaria infection. Group 3 will be challenged in parallel with Groups 1 (undergoing a third challenge) and 2 (undergoing a second challenge).

Biological: Blood-stage controlled human P. falciparum malaria infection

Interventions

Blood-stage controlled human P. falciparum malaria infection BIOLOGICAL

Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously.

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18 to 50 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 (GP).
• For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and on the day prior to blood-stage CHMI, and prior to the start of antimalarial treatment.
• Provide written informed consent.
• Agreement to permanently refrain from blood donation, as per current UK Blood Transfusion and Tissue Transplantation Services guidelines.
• Reachable (24 hours a day) by mobile phone during the period between CHMI and completion of antimalarial treatment.
• Willingness to take a curative anti-malarial regimen following CHMI.
• Answer all questions on the informed consent questionnaire correctly.
• For Groups 1-2: completion of primary or secondary challenge in the VAC063 trial, curative anti-malarials and follow-up (up until at least the C+28 visit).

You may not qualify if:

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
• Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator.
• Administration of immunoglobulins and/or any blood products at any time in the past.
• 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).
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• History of malaria chemoprophylaxis within 30 days prior to CHMI.
• Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
• History of allergic disease or reactions likely to be exacerbated by malaria infection.
• Pregnancy, lactation or willingness/intention to become pregnant during the study.
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of serious psychiatric condition likely to 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 units every week.
• Suspected or known injecting drug abuse in the 5 years preceding enrolment.
• Seropositive for hepatitis B surface antigen (HBsAg) at screening.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

CCVTM, University of Oxford, Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Salkeld J, Themistocleous Y, Barrett JR, Mitton CH, Rawlinson TA, Payne RO, Hou MM, Khozoee B, Edwards NJ, Nielsen CM, Sandoval DM, Bach FA, Nahrendorf W, Ramon RL, Baker M, Ramos-Lopez F, Folegatti PM, Quinkert D, Ellis KJ, Poulton ID, Lawrie AM, Cho JS, Nugent FL, Spence PJ, Silk SE, Draper SJ, Minassian AM. Repeat controlled human malaria infection of healthy UK adults with blood-stage Plasmodium falciparum: Safety and parasite growth dynamics. Front Immunol. 2022 Aug 22;13:984323. doi: 10.3389/fimmu.2022.984323. eCollection 2022.

  PMID: 36072606 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Study Officials

• Angela M Minassian, MBBS MA DPhil MRCP FRCPath

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: April 8, 2019
• Study Start: November 6, 2018
• Primary Completion: February 14, 2019
• Study Completion: February 14, 2019
• Last Updated: April 8, 2019

Record last verified: 2019-04

Locations

GB (1)