Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    vac063c
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03906474
Recruitment Status : Completed
First Posted : April 8, 2019
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
University of Oxford

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.


Condition or disease Intervention/treatment Phase
Malaria Biological: Blood-stage controlled human P. falciparum malaria infection Not Applicable

Detailed Description:

Nine to seventeen healthy adult volunteers, aged between 18 and 50 years, will be recruited and receive a blood-stage controlled human malaria infection (CHMI) at the CCVTM, Oxford. Of these volunteers, three will be newly recruited, malaria-naïve volunteers, who will receive a primary CHMI.

The remaining volunteers will be invited to be involved in this study, following previous participation in the VAC063 study (ClinicalTrials.gov Identifier: NCT02927145). VAC063 was a study to assess the safety, immune responses and efficacy of the new malaria vaccine RH5.1/AS01. As part of this study, control volunteers, who did not receive a vaccine, received a blood-stage CHMI, or "challenge", in order to compare to the vaccinated volunteers. Some control (unvaccinated) participants received two challenges and some received just one challenge, therefore, in this study, participants who previously took part in VAC063 will receive either a third or second malaria challenge.

Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously. Blood will then be taken at regular intervals to measure the parasite growth, quantify the sexual parasite forms and assess the immune response to primary, secondary or tertiary P. falciparum CHMI.

When volunteers are diagnosed with malaria, treatment with a standard antimalarial course of oral artemether-lumefantrine (Riamet) will be given over 3 days.

Volunteers who take part in this study will be involved in the trial for approximately 3 months.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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, and to Characterise Parasite Growth Dynamics
Actual Study Start Date : November 6, 2018
Actual Primary Completion Date : February 14, 2019
Actual Study Completion Date : February 14, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
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
Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously.

Experimental: Group 2
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
Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously.

Experimental: Group 3
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
Volunteers will be challenged with malaria by administering a small amount of P. falciparum infected blood intravenously.




Primary Outcome Measures :
  1. 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. [ Time Frame: 3 months ]
  2. 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). [ Time Frame: 3 months ]
    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.


Secondary Outcome Measures :
  1. P. falciparum specific immunogenicity following primary, secondary and tertiary P. falciparum blood-stage infection, as assessed by antibody, B cell and T cell responses [ Time Frame: 2 years ]
  2. Gametocytaemia following primary, secondary and tertiary P. falciparum blood-stage infection. [ Time Frame: 2 years ]
    Gametocytaemia will be measured by PCR.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.
  • Seropositive for HIV virus (antibodies to HIV) at screening
  • 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).
  • History of clinical malaria (any species - NOT applicable to prior challenge in VAC063 study for Groups 1 and 2).
  • Travel to a malaria endemic region during the study period or within the previous six months.
  • Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis.
  • 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 to allow Investigator to assess safety to participate.

  • History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection.
  • Laboratory evidence of G6PD deficiency at screening.
  • Laboratory evidence of haemoglobinopathy at screening.
  • 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.
  • Contraindications to the use of both Riamet and Malarone.
  • Any clinical condition known to prolong the QT interval.
  • Family history of congenital QT prolongation or sudden death.
  • Positive family history in both 1st and 2nd degree relatives < 50 years old for cardiac disease.
  • History of cardiac arrhythmia, including clinically relevant bradycardia.
  • Volunteer unable to be closely followed for social, geographic or psychological reasons.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03906474


Locations
Layout table for location information
United Kingdom
CCVTM, University of Oxford, Churchill Hospital
Oxford, United Kingdom, OX3 7LE
Sponsors and Collaborators
University of Oxford
Investigators
Layout table for investigator information
Principal Investigator: Angela M Minassian, MBBS MA DPhil MRCP FRCPath University of Oxford

Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03906474     History of Changes
Other Study ID Numbers: VAC063C
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Protozoan Infections
Parasitic Diseases