A Pilot Study to Test Activity of Antimalarial Drugs Against an Induced Malaria Infection in Healthy Volunteers

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2010-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a pilot study of a protocol for inducing a falciparum malaria infection in healthy volunteers in order to test the activity of novel agents being developed as drugs for the treatment of uncomplicated malaria. In this pilot study, 16 healthy male volunteers will be administered a low level malaria infection via infected human red blood cells. After 6 days they will be administered one of two registered antimalarial treatments (8 volunteers for each treatment) in order to define the rate of clearance of the infection. This information will be used to design similar future studies for the initial assessment of the efficacy of novel antimalarial drugs in development.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Experimental Falciparum Transmission to Anopheles

NCT02431637

Malaria

COMPLETED PHASE1

Effectiveness of OZ439 as a Gametocytocidal and Transmission Blocking Agent

NCT02431650

Malaria

COMPLETED PHASE1/PHASE2

Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers

NCT02453581

Malaria

COMPLETED PHASE1

SJ733 Induced Blood Stage Malaria Challenge Study

NCT02867059

Plasmodium Falciparum Malaria

COMPLETED PHASE1

First-in-Human Trial of Single Ascending Dose, Multiple Ascending Dose and Malaria Challenge Model in Healthy Participants

NCT03261401

Healthy

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a single-center, controlled, randomized, study using a BSP inoculum challenge as a model to assess the activity of antimalarial agents. The study will be conducted in 2 cohorts (n = 6 and n = 10). Cohort 2 will not commence until at least after day 12 of cohort 1 and review by Safety Review Team following day 9 exit of cohort 1. The participants will be randomized 1:1 to the two registered antimalarials. This is an enabling study using registered antimalarial drugs as reference treatments (one slow acting and one fast acting), aimed to inform trial design, endpoints and testing regimens for assessing new candidate antimalarial drugs in development. The study will follow the sequence of the challenge inoculation, reference treatment and follow-up.

Healthy male participants will be inoculated on Day 1 with \~1,800 Plasmodium falciparum-infected human erythrocytes administered intravenously. On an outpatient basis, participants will be monitored morning (AM) and night (PM) from day 3 to day 5 for adverse events and the unexpected early onset of symptoms, signs or parasitological evidence of malaria. On day 5 evening, participants will be admitted to the study unit and confined for safety monitoring and antimalarial treatment. Reference treatment administration will begin on the evening of Day 6 and continued on Day 7 and 8 (3 days of treatment).

If clinical or parasitologic evidence of malaria (either the identification of two or more malaria parasites on a malaria thick film, platelet count less than 100 x109/L, or the onset of clinical features of malaria) occurs before day 6 evening, allocated treatment will begin at this time.

Following treatment, participants will be followed up as inpatients for at least 86 hours, (4 evenings) to ensure tolerance of the therapy and clinical response, then if clinically well on an outpatient basis for safety and continued presence of malaria parasites via PCR and thick blood film review.

Adverse events will be monitored via telephone monitoring, within the clinical research unit and on outpatient review after malaria challenge inoculation and antimalarial study drug administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell antibodies will be drawn at baseline and at nominated times after malaria challenge.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy Non-smokers

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Artemether/lumefantrine tablets

Artemether (20 mg) and Lumefantrine (120 mg) tablets: Four tablets taken as a single dose twice a day with fatty food for three days (total dose of 24 tablets in 6 doses) on days 6-8

Group Type ACTIVE_COMPARATOR

Blood stage parasite (BSP) inoculum

Intervention Type BIOLOGICAL

Inoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1

Atovaquone/Proguanil HCl tablets

Atovaquone (250 mg) and Proguanil HCl (100 mg) tablets: Four tablets taken as a single dose daily for 3 days (total dose of 12 tablets) on days 6-8

Group Type ACTIVE_COMPARATOR

Blood stage parasite (BSP) inoculum

Intervention Type BIOLOGICAL

Inoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Blood stage parasite (BSP) inoculum

Inoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Males aged 18-45 years who do not live alone
* BMI within 18-30
* Understand the procedures and risks involved
* Contactable for the duration of the study
* Non-smokers and in good health
* Good venous access

Exclusion Criteria

* History of malaria
* Been in a malaria-endemic country within 12 months
* Evidence of cardiovascular risk
* Splenectomy
* History of severe allergic reactions after vaccination of infusion
* Any serious chronic illness
* Inherited genetic anomaly
* Any volunteers wishing to donate blood to the blood bank in the future
* Retinal or visual field changes
* Diagnosis of chronic severe psychiatric condition
* Hospitalisation within 5 years for psychiatric illness, suicide attempt or danger to self or others
* Receiving psychiatric drugs (some exceptions)
* Known QTc prolongation
* Family history of cardiac anomalies
* Recent or current therapy with an antibiotic or drug with potential antimalarial activity
* Known hypersensitivity to artemether or lumefantrine, atovaquone or proguanil hydrochloride or any of the excipients
* Concomitant use of any drug which is metabolised by the cytochrome enzyme CYP2D6 OR drugs that are known to prolong the QTc interval
* Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. Currently receiving or have previously received immunosuppressive therapy, including systemic steroids including ACTH or inhaled steroids in dosages which are associated with hypothalamicpituitary- adrenal axis suppression such as 1mg/kg/day of prednisone or its equivalent or chronic use of inhaled high potency corticosteroids
* Presence of acute infectious disease or fever
* Evidence of acute illness within the four weeks before trial prior to screening
* Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical examination, and/or laboratory studies including urinalysis
* Alcohol consumption greater than community norms
* A history of drug habituation, or any prior intravenous usage of an illicit substance
* Medical requirement for intravenous immunoglobulin or blood transfusions
* Participation in any investigational product study within the 8 weeks preceding the study
* Participation in any research study involving significant blood sampling, or blood donation to a blood bank during the 8 weeks preceding the study
* Have ever received a blood transfusion
* Positive test for HIV, Hepatitis B, hepatitis C, Human T-cell Lymphotropic Virus I \& II (HTLVI \& HTLVII), and syphilis
* Any clinically significant biochemical or haematologic abnormality (Hb must be ≥13.5g/dL)
* Ingestion of any poppy seeds within the 48 hours prior to the screening blood test
* Detection of any recreational drug listed in the urine drug screen

Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes