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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01055002




Registration number
NCT01055002
Ethics application status
Date submitted
21/01/2010
Date registered
25/01/2010
Date last updated
27/06/2011

Titles & IDs
Public title
A Pilot Study to Test Activity of Antimalarial Drugs Against an Induced Malaria Infection in Healthy Volunteers
Scientific title
A Pilot Phase II Study of the Efficacy of Antimalarial Drugs Against Plasmodium Falciparum by Experimental Challenge With a Low Dose of Blood Stage Parasites in Healthy Male Volunteers
Secondary ID [1] 0 0
QP09C08
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Non-smokers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Blood stage parasite (BSP) inoculum

Active Comparator: 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

Active Comparator: 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


Other interventions: Blood stage parasite (BSP) inoculum
Inoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parasite clearance rates by PCR
Timepoint [1] 0 0
1-7 days after drug treatment
Secondary outcome [1] 0 0
Parasite growth rates by PCR
Timepoint [1] 0 0
1-6 days after inoculation

Eligibility
Key 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
Minimum age
18 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Q-Pharm Clinics, Royal Brisbane and Women's Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Other
Name
Medicines for Malaria Venture
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Queensland Institute of Medical Research
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Q-Pharm Pty Limited
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
Trident Clinical Research Pty Ltd
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01055002
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James McCarthy, MD FRACP
Address 0 0
Queensland Institute of Medical Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications