Plasmodium Vivax MalariaPhase 1PvivaxNCT00935623
Clinical Trial for the Development of a Safe Malaria Challenge Model That Can be Reproduced in Humans
A Phase 1 study testing Malaria Challenge in people with Plasmodium Vivax Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial summary
The purpose of this study is to demonstrate that volunteers can be safely and reproducibly infected with Plasmodium vivax (P. vivax) by the bites of experimentally infected Anopheles dirus (An. dirus) mosquitoes carrying P. vivax sporozoites in their salivary glands. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Vivax Malaria
- What is being tested?
- Malaria Challenge
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2009to Sep 2011
- Phase
- Phase 1
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults (male or non-pregnant, non-lactating female) 18 to 55 years of age;
- Able to provide free and willing written informed consent to participate;
- A score at least 80% correct on a 10 question Assessment of Understanding;
- No plans to travel to a malaria endemic area during the course of the study;
- Duffy positive phenotype;
- Normal (non-deficient) G6PD phenotype (range : 4.6 to 13.5 u/gm hemoglobin);
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- Free of significant health problems as established by medical history and clinical examination completed prior to the study;
- Available to participate and reachable by phone for duration of study (approximately 9 months starting from screening).
- Only subjects with no or low cardiac risk factors according to the Gaziano study and a normal EKG will be included in the study
Who cannot join
- Pregnant or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge;
- Duffy negative phenotype;
- G6PD deficiency or have any hemoglobinopathy by history;
- Past infection with any species of malaria (as demonstrated by a positive thick smear) in the last 5 years;
- History of receipt of treatment or prophylaxis for malaria during the previous 6 months;
- History of receipt of malaria vaccine within the previous 5 years;
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- History of receipt of malaria challenge (being bitten by experimentally infected mosquitoes) within the previous 5 years;
- Plans to travel to malarious areas during the study period;
- Allergy to antimalarials or significant (e.g. systemic) hypersensitivity reactions to mosquito bites (local hypersensitivity reactions at the site of a mosquito bite are not an exclusion criterion);
- History of psoriasis (given its interaction with chloroquine);
- Use of any investigational or non-registered drug or vaccine within 30 days preceding the challenge or planned use during the study period;
- Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, during the study period (volunteers can withhold the use of these medications during the study period, at the minimum starting from 4 weeks before the challenge until 4 weeks after becoming parasitemic);
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and history of splenectomy;
- Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of challenge;
- For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day;
- Inhaled and topical steroids are allowed;
- A family history of congenital or hereditary immunodeficiency;
- Chronic or active neurologic disease including seizure disorder;
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination, or abnormal baseline laboratory screening tests:
- ALT above normal range (table 9);
- Creatinine above normal range (table 9);
- Hemoglobin below normal range (table 10);
- Platelet count below normal range (table 10);
- Total white cell count below normal range (table 10);
- Acute disease at the time of enrollment
- Acute disease is defined as the presence of a moderate or severe illness with or without fever;
- Challenge can be administered to persons with a minor illness, such as diarrhea or mild upper respiratory infection without fever (i.e., oral temperature < 38°C/100.4°F);
- Hepatomegaly, right upper quadrant abdominal pain or tenderness;
- Seropositive for HIV, hepatitis C virus (antibodies to HIV and HCV), and/or HBsAg;
- Administration of immunoglobulins and/or any blood products within the 3 months preceding challenge or planned administration during the study period;
- Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination;
- Inability to make follow-up visits;
- Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
WRAIR Clinical Trials Center
Silver Spring, Maryland, 20910
About this study
Official title: Development of a Safe and Reproducible Human Sporozoite Challenge Model for Plasmodium Vivax in Healthy Adults in the United States
The purpose of this study is to demonstrate that volunteers can be safely and reproducibly infected with Plasmodium vivax (P. vivax) by the bites of experimentally infected Anopheles dirus (An. dirus) mosquitoes carrying P. vivax sporozoites in their salivary glands.
Read the detailed description
The study is a proof-of-concept clinical investigation designed to develop a safe and practical sporozoite challenge model for Plasmodium vivax in humans with a goal of 100% infectivity rate. The development and standardization of such a model will make possible efficacy evaluations of candidate P. vivax vaccines in Phase 2a trials. This trial is conducted in collaboration with Armed Forces Research Institute of Medical Sciences (AFRIMS) investigators in Bangkok, Thailand, who will be recruiting adult blood donors from a pool of patients who present with active P. vivax infections in Thailand. Samples of P. vivax infected blood will be collected and fed via membrane feeding apparatus to colony-reared Anopheles dirus mosquitoes at the AFRIMS Entomology Lab. A portion of the same blood will meanwhile be screened for potential co-infections at the AFRIMS Retrovirology Laboratory. When screening tests have confirmed the presence of only P. vivax in the blood (no co-infections with other malaria species), and selected dissection on days 3-7 has revealed oocyst production in the blood-fed mosquitoes, the mosquitoes will be transported from the AFRIMS insectary in Thailand to the WRAIR insectary in the US by a standard procedure (herein described) including permits and assurance against accidental release of the infected mosquitoes. Transport will be conducted in compliance with Thai exporting and US importing requirements.
Our study will involve two cohorts, each to be challenged once, in the hope of demonstrating reproducibility of the entire challenge procedure. Each cohort comprises up to 6 healthy adult volunteers. The first cohort will be challenged with 5 bites from P. vivax-infected mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary gland).
If all six volunteers in the first cohort develop P. vivax infection, the same procedure will be repeated in the second cohort. If the first cohort has less than 100% infectivity rate, the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100% infectivity rate. Volunteers will be closely monitored post-infection, and will be treated with standard chloroquine and primaquine therapies when the infection becomes patent in the peripheral blood.
- Conditions
- Plasmodium Vivax Malaria
- Being tested
- Malaria Challenge
- Keywords
- Malaria, Plasmodium vivax
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Malaria ChallengeBiological
Malaria challenge
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | The first cohort will be challenged with 5 bites from P. vivax-infected mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary gland). Receives: Biological: Malaria Challenge |
| Cohort 2 | Experimental | If the first cohort has less than 100% infectivity rate, the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100% infectivity rate. Receives: Biological: Malaria Challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of erythrocytic stage P. vivax parasites by blood smear in volunteers during the 28 day period post challenge via the bites of five P. vivax-infected mosquitoes; Occurrence and intensity of solicited and unsolicited symptoms post challenge
Measured: 28 days post challenge
Secondary outcomes (1)
Parasitologic and clinical infections in challenge volunteers will be characterized by descriptive analysis of prepatent and patent periods, incubation period and time to resolution of signs and symptoms, and timing and number of relapses.
Measured: Cross-sectional
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2009 (estimated)
- Study start21 Apr 2009
- Primary completionJun 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Plasmodium Vivax MalariaStudies 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
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- United States Department of Defense, Walter Reed Army Institute of Research (WRAIR)
- Responsible party
- Sponsor
- Investigators
- Ilin Chuang, MD, MPH, Principal investigator, US Military Malaria Vaccine Program, Naval Medical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00935623
- Sponsor's protocol ID
- WRAIR 1518
- Other IDs
- HSRRB A-15209
- Acronym
- Pvivax
- Status last verified
- Aug 2018
- First submitted
- 7 Jul 2009
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Safe and Reproducible Human Sporozoite Challenge Model for Plasmodium Vivax in Healthy Adults in the United States
- ClinicalTrials.gov ID
- NCT00935623
- Acronym / sponsor ID
- Pvivax / WRAIR 1518
- Conditions
- Plasmodium Vivax Malaria
- Keywords
- Malaria, Plasmodium vivax
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- United States Department of Defense, Walter Reed Army Institute of Research (WRAIR)
- Study start
- 21 Apr 2009 (actual)
- Primary completion
- Jun 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 9 Jul 2009 (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.
The purpose of this study is to demonstrate that volunteers can be safely and reproducibly infected with Plasmodium vivax (P. vivax) by the bites of experimentally infected Anopheles dirus (An. dirus) mosquitoes carrying P. vivax sporozoites in their salivary glands.
Detailed description
The study is a proof-of-concept clinical investigation designed to develop a safe and practical sporozoite challenge model for Plasmodium vivax in humans with a goal of 100% infectivity rate. The development and standardization of such a model will make possible efficacy evaluations of candidate P. vivax vaccines in Phase 2a trials. This trial is conducted in collaboration with Armed Forces Research Institute of Medical Sciences (AFRIMS) investigators in Bangkok, Thailand, who will be recruiting adult blood donors from a pool of patients who present with active P. vivax infections in Thailand. Samples of P. vivax infected blood will be collected and fed via membrane feeding apparatus to colony-reared Anopheles dirus mosquitoes at the AFRIMS Entomology Lab. A portion of the same blood will meanwhile be screened for potential co-infections at the AFRIMS Retrovirology Laboratory. When screening tests have confirmed the presence of only P. vivax in the blood (no co-infections with other malaria species), and selected dissection on days 3-7 has revealed oocyst production in the blood-fed mosquitoes, the mosquitoes will be transported from the AFRIMS insectary in Thailand to the WRAIR insectary in the US by a standard procedure (herein described) including permits and assurance against accidental release of the infected mosquitoes. Transport will be conducted in compliance with Thai exporting and US importing requirements.
Our study will involve two cohorts, each to be challenged once, in the hope of demonstrating reproducibility of the entire challenge procedure. Each cohort comprises up to 6 healthy adult volunteers. The first cohort will be challenged with 5 bites from P. vivax-infected mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary gland).
If all six volunteers in the first cohort develop P. vivax infection, the same procedure will be repeated in the second cohort. If the first cohort has less than 100% infectivity rate, the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100% infectivity rate. Volunteers will be closely monitored post-infection, and will be treated with standard chloroquine and primaquine therapies when the infection becomes patent in the peripheral blood.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Malaria ChallengeThe first cohort will be challenged with 5 bites from P. vivax-infected mosquitoes each carrying at least a grade 2 sporozoite infection (>10 sporozoites in salivary gland). |
| Cohort 2 | Experimental | Biological: Malaria ChallengeIf the first cohort has less than 100% infectivity rate, the second cohort will be challenged with up to 10 grade 2 infective bites to ensure 100% infectivity rate. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy adults (male or non-pregnant, non-lactating female) 18 to 55 years of age;
- Able to provide free and willing written informed consent to participate;
- A score at least 80% correct on a 10 question Assessment of Understanding;
- No plans to travel to a malaria endemic area during the course of the study;
- Duffy positive phenotype;
Key exclusion criteria (33 listed)
- Pregnant or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge;
- Duffy negative phenotype;
- G6PD deficiency or have any hemoglobinopathy by history;
- Past infection with any species of malaria (as demonstrated by a positive thick smear) in the last 5 years;
- History of receipt of treatment or prophylaxis for malaria during the previous 6 months;
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 |
|---|---|---|
| Malaria ChallengeMalaria challenge | Biological | Cohort 1, Cohort 2 |
Primary outcome
Detection of erythrocytic stage P. vivax parasites by blood smear in volunteers during the 28 day period post challenge via the bites of five P. vivax-infected mosquitoes; Occurrence and intensity of solicited and unsolicited symptoms post challenge
Time frame: 28 days post challenge
1 secondary outcome
Parasitologic and clinical infections in challenge volunteers will be characterized by descriptive analysis of prepatent and patent periods, incubation period and time to resolution of signs and symptoms, and timing and number of relapses.
Time frame: Cross-sectional
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 16 Aug 2018.
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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.
Ilin Chuang, MD, MPH principal investigator
US Military Malaria Vaccine Program, Naval Medical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Malaria Challenge in people with Plasmodium Vivax Malaria, run by U.S. Army Medical Research and Development Command at 1 site in United States.
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 9 inclusion and 33 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 16 Aug 2018. 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 United States. 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 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.
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?
Detection of erythrocytic stage P. vivax parasites by blood smear in volunteers during the 28 day period post challenge via the bites of five P. vivax-infected mosquitoes; Occurrence and intensity of solicited and unsolicited symptoms post challenge (time frame: 28 days post challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Aug 2018.