MalariaPhase 1/2ChallengeIIINCT01585077
Exposure of Naive and Pre-immune Subjects to P. Vivax Challenge
A Phase 1/2 study testing P. vivax infected mosquito bites in people with Malaria, run by Socrates Herrera Valencia at 1 site in Colombia.
Trial summary
This study is a randomized clinical trial designed to compare the susceptibility of naive and pre-immune volunteers to infectious challenge with viable Plasmodium vivax sporozoites. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- P. vivax infected mosquito bites
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteColombia
- Study dates
- Oct 2012to Nov 2013
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Step 1:
- Age 15 to 60 years.
- Hemoglobin levels > 9g/dL.
- Presence of Current P. vivax infection.
- Absence of other Plasmodium species determined by thick blood smear and PCR.
- Blood parasite count of 0.1% or more.
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- Absence of other acute or chronic diseases.
- Being able to sign an informed consent form.
- Step 2:
- Healthy 18 to 45 years old man or non-pregnant women.
- To have the capacity to sign an informed consent in a free and voluntary way.
- To have an acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process.
- Obligatory use of adequate contraceptive method from beginning of recruitment and screening time up to three months after last immunization.
- Do not have chronic or acute diseases. These conditions will be determined by clinical history, physical exam and laboratory tests.
- To accept not traveling to malaria endemic areas during the clinical trial should
- To have telephone at home or mobile phone that permit permanent contact for follow up
- Being willing to participated during both steps of the clinical trial.
Who cannot join
- Step 1:
- history of blood transfusion in the last six months.
- Pregnancy in women.
- Have received antimalarial treatment before the diagnosis.
- Step 2:
- Pregnant or nursing women.
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- History of moderate or severe insect, or food allergies.
- G-6PD deficiency or any Hb genetic defect.
- Symptoms, signs or data from laboratory test that suggests any systemic disorder like renal, hepatic, cardiovascular, pulmonary, psychiatric disorders or other illnesses that could interfere with results of clinical trial or could compromise the health of the volunteer.
- To have antibodies against hepatitis C, VIH, or hepatitis B superficial antigen and/or hepatitis B core antibodies.
- To have any abnormality in the parameters assessed by blood laboratory tests
- Presence or history of an auto-immune disease.
- History of surgical removal of the spleen (splenectomy).
- Use of medical treatment known to alter the immune system before 3 months to recruitment.
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Malaria Vaccine and Drug development Center (MVDC)
Cali, Valle del Cauca Department
About this study
Official title: Comparison of the Susceptibility of Naive and Pre-immune Volunteers to Infectious Challenge With Viable Plasmodium Vivax Sporozoites.
This study is a randomized clinical trial designed to compare the susceptibility of naive and pre-immune volunteers to infectious challenge with viable Plasmodium vivax sporozoites. The term preimmune hereafter denoted only previous experience with infection by this parasite and not a definite state of immunity to malaria infection. The study hypothesis is that pre-immune volunteers present a delayed onset of malaria clinical and parasitological manifestations when compared to naive individuals. The development of this study will establish a protocol for evaluating the effectiveness of vaccine candidates against P. vivax in subsequent Phases IIa and IIb clinical trials.
Read the detailed description
This study is a prospective controlled, blinded clinical trial, designed to establish the differences on infectivity of an infectious challenge with P. vivax sporozoites between human volunteers with and without history of malaria.
Study subjects
This study will require the involvement of two types of volunteers:
- Parasite donors: 5-15 P. vivax-infected patients who will serve as parasites donors for experimental infection of mosquitoes, who will be enrolled in the endemic area.
- Volunteers for infectious challenge Two other groups of volunteers will be exposed to mosquitoes infected with P. vivax sporozoites. A group of 7 people without previous exposure to malaria (naive) and another 12 people with a history of previous malaria infection (pre-immune).
Methodology
- Recruitment of infected patients Parasite donors will be recruited among P. vivax infected patients attending a diagnostic center in the endemic area.
- Infection of mosquitoes Blood from donors will be used to feed three days old mosquitoes by artificial membrane feeding technique. At day 7 a sample of mosquitoes will be examined to determine the degree of infection by dissection of the mosquito gut. On day 14, a small amount of mosquitoes with a good degree of infectivity will be used to infect challenged volunteers.
- Recruitment of pre-immune and naive volunteers Volunteers for the challenge will be recruited both in the city of Cali, non-endemic region, and in Buenaventura, a malaria endemic region, through various activities such as conferences, meetings and other means approved by the IRB like posters and flyers.
Infection of volunteers
The "feeding cage" will be placed on the forearm of a volunteer for 10 minutes, allowing that the feeding window, wich will be covered by a mesh surface be placed against the volunteer's skin.
Follow Up
Volunteers will be educated about the signs and symptoms of malaria and they will have a daily telephone contact during the first 6 days.
Between days 7 and 23 the volunteers will be asked to go to the Clinical Trials Unit daily in order to establish the presence or absence of disease through thick blood smear and samples will be collected for retrospective real time PCR P. vivax.
From day 23 until day 31, volunteers will receive physical and laboratory evaluation every other day and will have daily telephone contact.
Once the patients present signs and symptoms of the disease curative treatment will be immediately provided, and 15 ml of blood will be drawn, which will be used for immune response assessment.
If the volunteers do not develop the disease during the follow-up period, on day 31 they will be given antimalarial treatment.
Treatment
Volunteers will be treated with antimalarial drugs approved by the Colombian Ministry of Social Protection: chloroquine (three (3) doses: 600 mg initially, followed by 450mg at 24, and 48 hours), associated with primaquine (30mg/día) for 14 days. All the volunteers will be asked to return two weeks after starting treatment for a thick blood smear test to ensure cure of malaria.
- Conditions
- Malaria
- Being tested
- P. vivax infected mosquito bites
- Keywords
- Plasmodium vivax, Malaria, Challenge, Anopheles albimanus
- Medical subject headings
- Malaria, Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P. vivax infected mosquito bitesBiological
All volunteers will receive one dose of 2-4 P. vivax infected mosquito bites. All the mosquitoes will correspond to the same mosquito batch to make sure that all volunteers receive the same P. vivax strain.
| Study group | Role | What they receive |
|---|---|---|
| Naive volunteers | Experimental | Volunteers without previous exposure to malaria, and negative antibody titers (<1:20) against native protein of P. vivax. Receives: Biological: P. vivax infected mosquito bites |
| Pre-immune volunteers | Experimental | Volunteers with previous exposure to malaria, and positive antibody titers against native protein of P. vivax Receives: Biological: P. vivax infected mosquito bites |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pre-patent period onset
begining at day 7 after mosquito bites exposure, both groups of volunteers will be evaluated with dayly Thick blood smear to compare the malaria onset between the pre-immune and naive groups.
Measured: Two months after the challenge
Secondary outcomes (1)
Immune response
Malaria signs and symptoms will be assessed to stablish severity and frequency of appearence in both groups: Pre-immune and naive.
Blood sample will be taken at the end of the study to determine the differences in celular and humoral immune responses in both study groups.
Measured: Two months after the malaria challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2012 (estimated)
- Study startOct 2012
- Primary completionJun 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Socrates Herrera Valencia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Socrates Herrera Valencia, Malaria Vaccine and Drug Development Center
- Investigators
- Sócrates Herrera, MD, Principal investigator, Malaria Vaccine and Drug Development Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01585077
- Sponsor's protocol ID
- CIV - 08 - 102010
- Acronym
- ChallengeIII
- Status last verified
- Jan 2014
- First submitted
- 23 Apr 2012
- Last updated
- 15 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Herrera S, Solarte Y, Jordan-Villegas A, Echavarria JF, Rocha L, Palacios R, Ramirez O, Velez JD, Epstein JE, Richie TL, Arevalo-Herrera M. Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers. Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):4-11. doi: 10.4269/ajtmh.2011.09-0498.
PubMed 21292872Herrera S, Fernandez O, Manzano MR, Murrain B, Vergara J, Blanco P, Palacios R, Velez JD, Epstein JE, Chen-Mok M, Reed ZH, Arevalo-Herrera M. Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors. Am J Trop Med Hyg. 2009 Nov;81(5):740-6. doi: 10.4269/ajtmh.2009.09-0194.
PubMed 19861603Arevalo-Herrera M, Forero-Pena DA, Rubiano K, Gomez-Hincapie J, Martinez NL, Lopez-Perez M, Castellanos A, Cespedes N, Palacios R, Onate JM, Herrera S. Plasmodium vivax sporozoite challenge in malaria-naive and semi-immune Colombian volunteers. PLoS One. 2014 Jun 25;9(6):e99754. doi: 10.1371/journal.pone.0099754. eCollection 2014.
PubMed 24963662
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Susceptibility of Naive and Pre-immune Volunteers to Infectious Challenge With Viable Plasmodium Vivax Sporozoites.
- ClinicalTrials.gov ID
- NCT01585077
- Acronym / sponsor ID
- ChallengeIII / CIV - 08 - 102010
- Conditions
- Malaria
- Keywords
- Plasmodium vivax, Malaria, Challenge, Anopheles albimanus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Socrates Herrera ValenciaUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Jun 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 25 Apr 2012 (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 study is a randomized clinical trial designed to compare the susceptibility of naive and pre-immune volunteers to infectious challenge with viable Plasmodium vivax sporozoites. The term preimmune hereafter denoted only previous experience with infection by this parasite and not a definite state of immunity to malaria infection. The study hypothesis is that pre-immune volunteers present a delayed onset of malaria clinical and parasitological manifestations when compared to naive individuals. The development of this study will establish a protocol for evaluating the effectiveness of vaccine candidates against P. vivax in subsequent Phases IIa and IIb clinical trials.
Detailed description
This study is a prospective controlled, blinded clinical trial, designed to establish the differences on infectivity of an infectious challenge with P. vivax sporozoites between human volunteers with and without history of malaria.
Study subjects
This study will require the involvement of two types of volunteers:
- Parasite donors: 5-15 P. vivax-infected patients who will serve as parasites donors for experimental infection of mosquitoes, who will be enrolled in the endemic area.
- Volunteers for infectious challenge Two other groups of volunteers will be exposed to mosquitoes infected with P. vivax sporozoites. A group of 7 people without previous exposure to malaria (naive) and another 12 people with a history of previous malaria infection (pre-immune).
Methodology
- Recruitment of infected patients Parasite donors will be recruited among P. vivax infected patients attending a diagnostic center in the endemic area.
- Infection of mosquitoes Blood from donors will be used to feed three days old mosquitoes by artificial membrane feeding technique. At day 7 a sample of mosquitoes will be examined to determine the degree of infection by dissection of the mosquito gut. On day 14, a small amount of mosquitoes with a good degree of infectivity will be used to infect challenged volunteers.
- Recruitment of pre-immune and naive volunteers Volunteers for the challenge will be recruited both in the city of Cali, non-endemic region, and in Buenaventura, a malaria endemic region, through various activities such as conferences, meetings and other means approved by the IRB like posters and flyers.
Infection of volunteers
The "feeding cage" will be placed on the forearm of a volunteer for 10 minutes, allowing that the feeding window, wich will be covered by a mesh surface be placed against the volunteer's skin.
Follow Up
Volunteers will be educated about the signs and symptoms of malaria and they will have a daily telephone contact during the first 6 days.
Between days 7 and 23 the volunteers will be asked to go to the Clinical Trials Unit daily in order to establish the presence or absence of disease through thick blood smear and samples will be collected for retrospective real time PCR P. vivax.
From day 23 until day 31, volunteers will receive physical and laboratory evaluation every other day and will have daily telephone contact.
Once the patients present signs and symptoms of the disease curative treatment will be immediately provided, and 15 ml of blood will be drawn, which will be used for immune response assessment.
If the volunteers do not develop the disease during the follow-up period, on day 31 they will be given antimalarial treatment.
Treatment
Volunteers will be treated with antimalarial drugs approved by the Colombian Ministry of Social Protection: chloroquine (three (3) doses: 600 mg initially, followed by 450mg at 24, and 48 hours), associated with primaquine (30mg/día) for 14 days. All the volunteers will be asked to return two weeks after starting treatment for a thick blood smear test to ensure cure of malaria.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naive volunteers | Experimental | Biological: P. vivax infected mosquito bitesVolunteers without previous exposure to malaria, and negative antibody titers (<1:20) against native protein of P. vivax. |
| Pre-immune volunteers | Experimental | Biological: P. vivax infected mosquito bitesVolunteers with previous exposure to malaria, and positive antibody titers against native protein of P. vivax |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Step 1:
- Step 2:
Key exclusion criteria (14 listed)
- Step 1:
- Step 2:
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 |
|---|---|---|
| P. vivax infected mosquito bitesAll volunteers will receive one dose of 2-4 P. vivax infected mosquito bites. All the mosquitoes will correspond to the same mosquito batch to make sure that all volunteers receive the same P. vivax strain. | Biological | Naive volunteers, Pre-immune volunteers |
Primary outcome
Pre-patent period onset
Time frame: Two months after the challenge
begining at day 7 after mosquito bites exposure, both groups of volunteers will be evaluated with dayly Thick blood smear to compare the malaria onset between the pre-immune and naive groups.
1 secondary outcome
Immune response
Time frame: Two months after the malaria challenge
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 15 Jan 2014.
- Background: PubMed 21292872Herrera S, Solarte Y, Jordan-Villegas A, Echavarria JF, Rocha L, Palacios R, Ramirez O, Velez JD, Epstein JE, Richie TL, Arevalo-Herrera M. Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers. Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):4-11. doi: 10.4269/ajtmh.2011.09-0498.
- Background: PubMed 19861603Herrera S, Fernandez O, Manzano MR, Murrain B, Vergara J, Blanco P, Palacios R, Velez JD, Epstein JE, Chen-Mok M, Reed ZH, Arevalo-Herrera M. Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors. Am J Trop Med Hyg. 2009 Nov;81(5):740-6. doi: 10.4269/ajtmh.2009.09-0194.
- Derived from this study: PubMed 24963662Arevalo-Herrera M, Forero-Pena DA, Rubiano K, Gomez-Hincapie J, Martinez NL, Lopez-Perez M, Castellanos A, Cespedes N, Palacios R, Onate JM, Herrera S. Plasmodium vivax sporozoite challenge in malaria-naive and semi-immune Colombian volunteers. PLoS One. 2014 Jun 25;9(6):e99754. doi: 10.1371/journal.pone.0099754. eCollection 2014.
- Malaria Vaccine and Drug Development Center web pageLink provided by the sponsor.
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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.
Sócrates Herrera, MD principal investigator
Malaria Vaccine and Drug Development Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing P. vivax infected mosquito bites in people with Malaria, run by Socrates Herrera Valencia at 1 site in Colombia.
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 17 inclusion and 14 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 15 Jan 2014. 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 Colombia. 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?
Pre-patent period onset (time frame: Two months after the challenge). 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 NCT01585077, which also lists 3 linked publications.
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 15 Jan 2014.