A Study of Blood-stage Controlled Human Plasmodium Falciparum Malaria Infection in Tanzania

NCT04788862 | Completed DMC

• 1 other identifier: VAC083
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single-centre, open label trial to determine the safety and feasibility of CHMI model using Plasmodium falciparum-infected cryopreserved erythrocytes administered to healthy Tanzanian adults with varying prior exposure to P. falciparum.

Conditions

Malaria; Plasmodium Falciparum

Keywords

Malaria Challenge; Controlled Human Malaria Challenge

Outcome Measures

Primary Outcomes (4)

• Occurrence of adverse events to assess the safety of controlled blood-stage P. falciparum

  Frequency and severity of clinical and laboratory Adverse Events and Serious Adverse Events

  98 days

• Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum

  Proportion of participants who develop detectable parasitaemia post-CHMI as measured by qPCR

  28 days

• Development of parasitaemia to assess the feasibility of controlled blood-stage P. falciparum

  Proportion of participants who develop sustained parasitaemia detectable by qPCR that is then spontaneously cleared

  28 days

• Parasite multiplication rates to assess the feasibility of controlled blood-stage P. falciparum

  Determine parasite multiplication rates as calculated by fitting established models to quantitative PCR data, as routinely done in the published studies (Payne et al., JID 2016; Minassian et al., submitted)

  28 days

Secondary Outcomes (5)

• Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis

  98 days

• Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis

  98 days

• Cellular and Humoral Immune responses level at C-1, C+7, C+14, C+21, C+28, C+56, C+98 and diagnosis

  98 days

• To determine the effect of pre-exposure to malaria on parasite multiplication rates following controlled blood-stage P. falciparum infection.

  28 days

• To determine if malaria infection following inoculation of P. falciparum is caused by the inoculum parasite strain and not wild-type strains

  28 days

Study Arms (2)

Group 1: High prior P. falciparum exposure

EXPERIMENTAL

6 participants with high previous malaria exposure will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes (planned dose of 1000 iRBCs) of the chloroquine-susceptible 3D7 strain.

Biological: P. falciparum infected erythrocytes

Group 2: Low prior P. falciparum exposure

EXPERIMENTAL

6 participants with no or low previous malaria exposure will be infected via IV administration of Plasmodium falciparum-infected human erythrocytes (planned dose of 1000 iRBCs) of the chloroquine-susceptible 3D7 strain.

Biological: P. falciparum infected erythrocytes

Interventions

P. falciparum infected erythrocytes BIOLOGICAL

Chloroquine sensitive P. falciparum 3D7-infected red blood cells, thawed and prepared under strict aseptic conditions, will be used as a challenge agent.

Group 1: High prior P. falciparum exposure; Group 2: Low prior P. falciparum exposure

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteer being adult male aged ≥ 18 and ≤ 35 years, and in good health.
• Volunteer a resident in Bagamoyo town or rural areas of Bagamoyo district for the past 6 months
• Able and willing to complete the informed consent process conducted in English
• Volunteer has adequate understanding of the procedures of the study and is able and willing (in the investigator's opinion) to comply with all study requirements.
• Volunteer is willing to complete an informed consent questionnaire and is able to answer all questions correctly in a maximum of two attempts.
• Volunteer is able to communicate well with the investigator and is willing to be monitored in an inpatient setting for 28 days after challenge with infected erythrocytes.
• The volunteer agrees to refrain from blood donation throughout the study period.
• Volunteer agrees to refrain from intensive physical exercise (disproportionate to the volunteer's usual daily activity or exercise routine) during the malaria challenge period.
• Volunteer has signed written informed consent to participate in the trial.

You may not qualify if:

• Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, gastrointestinal, renal, hepatic, neurological, dermatological (e.g. psoriasis, contact dermatitis etc.), allergy, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the volunteer during the study or interfere with the interpretation of the study results.
• A heightened risk of cardiovascular disease, as determined by: an estimated ten-year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives \<50 years old.
• Body mass index (BMI) of \<18 or \>30 Kg/m2
• A medical history of functional asplenia.
• History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
• Confirmed parasite positive by PCR a day before challenge i.e., at C-1.
• Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
• Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral antihistamines exempted) or expected use of such during the study period
• Any recent or current systemic therapy with an antibiotic or drug with potential antimalarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (allowable time frame for use at the Investigator's discretion).
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
• Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
• History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
• Previous participation in any malaria investigational product study (allowable time frame for use at the Investigator's discretion)
• Known hypersensitivity to or contra-indications (including co-medication) for use of chloroquine, artemether-lumefantrine, Primaquine or history of severe (allergic) reactions to blood transfusion.
• Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.

Sponsors & Collaborators

• University of Oxford: lead
• Ifakara Health Institute: collaborator

Study Sites (1)

Ifakara Health Institute

Bagamoyo, Tanzania

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Study Officials

• Angela Minassian, Dr

  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: February 25, 2021
• First Posted: March 9, 2021
• Study Start: July 18, 2022
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05

Locations

TA (1)