Susceptibility of Gambian Adults to PfSPZ-Challenge Infection in the Controlled Human Malaria Infection Model

NCT03496454 | Completed DMC

• 1 other identifier: SCC 1529
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Controlled human malaria infection (CHMI) is an important tool for the assessment of the efficacy of novel malaria vaccines and drugs prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo and thus allows for the assessment of the natural acquisition and loss of malaria immunity. This may be particularly useful in individuals from endemic areas with changing levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria could be a valuable tool to accelerate malaria vaccine development and inform malaria control programs of changing immunity levels and related disease presentations. In this trial, the investigators intend to study the effect of pre-exposure to Plasmodium falciparum (Pf) on parasite kinetics, clinical symptoms and immunity after CHMI by PfSPZ Challenge in Gambian adults. Based on a well-defined sero-profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection.

Conditions

Malaria

Keywords

malaria; infection; controlled

Outcome Measures

Primary Outcomes (2)

• frequency and magnitude of adverse events

  Frequency, incidence, nature and magnitude of adverse events

  28 days

• time to first detection of parasites and parasites density

  to compare time to first detection of parasites and parasite density at first detection by 18S qPCR and varATS qPCR. This time to patency and first parasite density are important indicators of pre-erythrocytic immunity and will be compared between cohorts A and B

  28 days

Secondary Outcomes (3)

• Time to Pf-NF54 parasitemia

  28 days

• parasite growth

  day 5 to day 28

• differences in immune responses

  28 days

Study Arms (1)

PfSPZ Challenge

OTHER

this is a basic sciences protocol designed to study the effect of pre-exposure to Plasmodium falciparum (Pf) on malaria parasite kinetics, clinical symptoms and immunity after Controlled Human Malaria Infection by administration of an injection PfSPZ Challenge in Gambian adults. Based on a well-defined serological profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection. The classification as a clinical trial results from the administration of the PfSPZ Challenge to the healthy volunteers

Other: PfSPZ Challenge

Interventions

PfSPZ Challenge OTHER

The administration of an injection PfSPZ Challenge in Gambian adults

PfSPZ Challenge

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Males aged ≥ 18 and ≤ 35 years and in good health
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males aged ≥ 18 and ≤ 35 years and in good health;
• At least 4 completed years of secondary education;
• Adequate understanding of the procedures of the study in English language;
• Willing (in the investigator's opinion) to comply with all study requirements;
• Willing to complete an informed consent questionnaire and is able to answer all questions correctly;
• Signed written informed consent to participate in the trial;
• Willing to take a course of curative anti-malaria medication;
• Able to communicate well with the investigator and is available to attend all study visits;
• Willing to stay in a hotel close to the trial centre OR willing to be hospitalized in the CSD of MRCG during a part of the study (day 5 post-infection until day 3 after treatment);
• Reachable (24/7) by mobile telephone throughout the entire study period;
• Agrees to refrain from blood donation or for other purposes throughout the study period and after the end of their involvement in the study according to the local blood banking eligibility criteria.
• Agrees to refrain from intensive physical exercise (disproportionate to the participant's usual daily activity or exercise routine) during the malaria challenge period;
• Hb ≥12 g/dl.

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, renal, hepatic, neurological, dermatological, endocrine,malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following
• Body weight \<50 kg or Body Mass Index (BMI) \<18 or \>30 kg/m2 at screening.
• 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's, 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.
• A medical history of functional asplenia, G6PD disease or α-thalassaemia disease.
• Positive test for sickle cell disease.
• History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
• 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 anti-histamines exempted) or expected use of such during the study period.
• Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (Allowable timeframe 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.
• Suspicion or history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
• Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
• qPCR positive for Pf parasites at screening or previous participation in any malaria (vaccine) study.
• Known hypersensitivity to artemether-lumefantrine.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Radboud University Medical Center: collaborator
• Sanaria Inc.: collaborator

Study Sites (1)

MRC Unit

Fajara, The Gambia

Location

Related Publications (1)

• Achan J, Reuling IJ, Yap XZ, Dabira E, Ahmad A, Cox M, Nwakanma D, Tetteh K, Wu L, Bastiaens GJH, Abebe Y, Manoj A, Kaur H, Miura K, Long C, Billingsley PF, Sim BKL, Hoffman SL, Drakeley C, Bousema T, D'Alessandro U. Serologic Markers of Previous Malaria Exposure and Functional Antibodies Inhibiting Parasite Growth Are Associated With Parasite Kinetics Following a Plasmodium falciparum Controlled Human Infection. Clin Infect Dis. 2020 Jun 10;70(12):2544-2552. doi: 10.1093/cid/ciz740.

  PMID: 31402382 DERIVED

MeSH Terms

Conditions

Malaria; Infections

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 12, 2018
• Study Start: March 29, 2018
• Primary Completion: May 3, 2018
• Study Completion: December 5, 2018
• Last Updated: January 16, 2019

Record last verified: 2019-01

Locations

TH (1)