HealthyPhase 1/2NCT01055002
A Pilot Study to Test Activity of Antimalarial Drugs Against an Induced Malaria Infection in Healthy Volunteers
A Phase 1/2 study testing Blood stage parasite (BSP) inoculum in people with Healthy and Non-smokers, run by Medicines for Malaria Venture at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy, Non-smokers
- What is being tested?
- Blood stage parasite (BSP) inoculum
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteAustralia
- Study dates
- Jan 2010to Aug 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 31Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Australia1 site
Q-Pharm Clinics, Royal Brisbane and Women's Hospital
Brisbane, Queensland, 4006
About this study
Official 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
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.
Read the detailed description
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
- Healthy, Non-smokers
- Being tested
- Blood stage parasite (BSP) inoculum
- Keywords
- Health male volunteers, Male volunteers aged 18-45 years, Non-smokers and in good health
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood stage parasite (BSP) inoculumBiological
Inoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1
| Study group | Role | What they receive |
|---|---|---|
| Artemether/lumefantrine tablets | Active comparator | 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 Receives: Biological: Blood stage parasite (BSP) inoculum |
| Atovaquone/Proguanil HCl tablets | Active comparator | 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 Receives: Biological: Blood stage parasite (BSP) inoculum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasite clearance rates by PCR
Measured: 1-7 days after drug treatment
Secondary outcomes (1)
Parasite growth rates by PCR
Measured: 1-6 days after inoculation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2010 (estimated)
- Study startJan 2010
- Primary completionJul 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Queensland Institute of Medical Research, Q-Pharm Pty Limited, Trident Clinical Research Pty Ltd
- Investigators
- James McCarthy, MD FRACP, Principal investigator, Queensland Institute of Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01055002
- Sponsor's protocol ID
- QP09C08
- Status last verified
- Jun 2011
- First submitted
- 21 Jan 2010
- Last updated
- 27 Jun 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
McCarthy JS, Sekuloski S, Griffin PM, Elliott S, Douglas N, Peatey C, Rockett R, O'Rourke P, Marquart L, Hermsen C, Duparc S, Mohrle J, Trenholme KR, Humberstone AJ. A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs. PLoS One. 2011;6(8):e21914. doi: 10.1371/journal.pone.0021914. Epub 2011 Aug 22.
PubMed 21887214
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01055002
- Acronym / sponsor ID
- QP09C08
- Conditions
- Healthy, Non-smokers
- Keywords
- Health male volunteers, Male volunteers aged 18-45 years, Non-smokers and in good health
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Queensland Institute of Medical Research, Q-Pharm Pty Limited, Trident Clinical Research Pty Ltd
- Study start
- Jan 2010
- Primary completion
- Jul 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 25 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Artemether/lumefantrine tablets | Active comparator | Biological: Blood stage parasite (BSP) inoculumArtemether (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 |
| Atovaquone/Proguanil HCl tablets | Active comparator | Biological: Blood stage parasite (BSP) inoculumAtovaquone (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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (31 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood stage parasite (BSP) inoculumInoculum of human red blood cells infected with falciparum malaria administered intravenously on Day 1 | Biological | Artemether/lumefantrine tablets, Atovaquone/Proguanil HCl tablets |
Primary outcome
Parasite clearance rates by PCR
Time frame: 1-7 days after drug treatment
1 secondary outcome
Parasite growth rates by PCR
Time frame: 1-6 days after inoculation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2011.
- Derived from this study: PubMed 21887214McCarthy JS, Sekuloski S, Griffin PM, Elliott S, Douglas N, Peatey C, Rockett R, O'Rourke P, Marquart L, Hermsen C, Duparc S, Mohrle J, Trenholme KR, Humberstone AJ. A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs. PLoS One. 2011;6(8):e21914. doi: 10.1371/journal.pone.0021914. Epub 2011 Aug 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James McCarthy, MD FRACP principal investigator
Queensland Institute of Medical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Blood stage parasite (BSP) inoculum in people with Healthy and Non-smokers, run by Medicines for Malaria Venture at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parasite clearance rates by PCR (time frame: 1-7 days after drug treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01055002, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2011.