MalariaPhase 2NCT02083068
Evaluation of the Protective Efficacy of a Vaccine Derived From the Synthetic CS Protein of Plasmodium Vivax
A Phase 2 study testing Vaccine PvCS N+C+R, Vaccine PvCS N+C and SSN Montanide ISA-51 in people with Malaria, run by Malaria Vaccine and Drug Development Center at 1 site in Colombia.
Trial summary
This is a randomized, double-blind, controlled, which seeks to compare two groups of volunteers (naive and previously exposed to malaria) who were made 3 immunizations with a synthetic derivative of the CS protein of Plasmodium vivax in order to determine their protective efficacy. 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?
- Vaccine PvCS N+C+R, Vaccine PvCS N+C and SSN Montanide ISA-51
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteColombia
- Study dates
- Aug 2014to Jul 2017
- Phase
- Phase 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
- Naïve group
- Healthy men and women aged 18-45 years. Signing freely and voluntary informed consent , accompanied by two witnesses who also sign.
- Not have a history of malaria infection. For women, use of adequate contraception from the star restriction to be lifted by a doctor for contraception study. Accept not to travel to areas considered endemic for malaria during Trophies infectious period (1 month ) ( Buenaventura , Tierralta , Pretoria , Tumaco ,Urabá and Bajo Cauca) .
- Be reachable by phone throughout the study period. Being Duffy positive ( Fy +) . Levels of hemoglobin ( Hb) > 11 g / dl. Availability to participate during the period in which they develop the study. Do not be participating in another clinical study
- 2. Preimmune group
- Healthy men and women aged 18-45 years. Signing freely and voluntary informed consent , accompanied by two witnesses who also sign .
Show all 17Show fewer
- Having a history of infection (s ) and serological tests for malaria positive for P. vivax.
- For women, use adequate contraception from the start restriction to be lifted by a doctor for contraception study .
- Accept not to travel to areas considered endemic for malaria during Trophies infectious period (1 month ) ( Buenaventura , Tierralta , Pretoria , Tumaco Urabá and Bajo Cauca) .
- Be reachable by phone throughout the study period. Availability to participate during the period in which they develop the study.
- 3. Voluntary blood donors
- Healthy men and women aged 18-45 years.
- Be positive diagnosis of P. vivax determined by thick smear examination .
- The patient must not have circulating malaria parasites such as P. falciparum or P. malariae .
- Have a parasitemia ≥ 0.1 %. by thick smear .
- Hb ≥ 9 g / dL at the time of diagnosis of malaria.
- The patient must have the capacity to provide informed consent freely and voluntarily . Should be illiterate may assert its decision to participate by putting their fingerprint in the format consent. Minors who are between 15 and 17 and wishing to participate must sign the informed consent and one of its Parents must sign the informed consent, accompanied by 2 witnesses who also sign
Who cannot join
- Step 1
- Negative IFAT (< 1:20) for P. vivax on screening tests
- Other criteria used in the case of naive volunteers, except a history of having lived in an endemic area for the past 6 months.
- Step 2 Patients that have chronic or acute disease, different from malaria by P. vivax.
- Having a history of disease or clinical conditions that according to medical criteria might increase significantly the risk related with participation on this study Hemoglobin levels <9 g/dL at the time of recruitment Have received antimalarial treatment before the diagnosis
Trial locations and contacts
1 site in 1 country.
Colombia1 site
Malaria Vaccine and Drug Development Center
Cali, Valle del Cauca Department
About this study
This is a randomized, double-blind, controlled, which seeks to compare two groups of volunteers (naive and previously exposed to malaria) who were made 3 immunizations with a synthetic derivative of the CS protein of Plasmodium vivax in order to determine their protective efficacy. Then volunteers will be subject to an infectious challenge to assess the infectivity of gametocytes in the blood early stage of P. vivax in Anopheles albimanus mosquitoes.
Read the detailed description
This study is a prospective controlled, blinded clinical trial, designed to establish the protective efficacy induced by the vaccine PvCSP 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 immunization: Two other groups of volunteers will be immunized with the vaccine PvCSP. A group of 16 people without previous exposure to malaria (naive) and another 16 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 immunization stage 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.
Immunization: Volunteers will be immunized with the vaccine (n=16) or placebo (n=16).
Follow Up Volunteers will be under medical vigilance during the first hour following the immunization to detect any adverse reaction. After the first hour period a medical exam will be made. Eight hours after immunization, each volunteer will be telephoned to assess physical condition. Any adverse event (AE) will be registered.
Subsequent follow up will be made on the day next to immunization and 1 or 2 weeks before the next immunization by a new clinical evaluation and AE report. Volunteers will be educated to contact the research staff at any moment.
Infection of volunteers Immunized volunteers will be challenged on day ~150 of the study, 1 month after the third immunization by the bite of 3±1 infected mosquitos. 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.
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
- Vaccine PvCS N+C+R, Vaccine PvCS N+C, SSN Montanide ISA-51
- Keywords
- Malaria, vaccine, P. vivax
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaccine PvCS N+C+RBiological
Vaccine PvCS N+C+R 60 mcg, freeze dried powder, Batch n°P0RGB, Exp: 18.10.2015 At month 2 and 6
Vaccine PvCS N+CBiological
Vaccine PvCS N+C 60 mcg, freeze dried powder, Batch n°P0RGA, Exp: 18.10.2015, at month 0
SSN Montanide ISA-51Biological
SSN Montanide ISA-51 1 mL
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | 10 individuals per sub- group to be immunized with the Vaccine PvCS N+C at month 0 and the Vaccine PvCS N+C+R at months 2 and 6 Receives: Biological: Vaccine PvCS N+C+R; Biological: Vaccine PvCS N+C |
| Control | Placebo comparator | six individuals for each sub- group to be immunized with placebo SSN Montanide ISA-51 Receives: Biological: SSN Montanide ISA-51 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protective efficacy against P. vivax infection on volunteers exposed to infected mosquito bites
Vaccine protective efficacy against P. vivax infection on volunteers exposed to infected mosquito bites
Measured: Thirty days after the last immunization
Secondary outcomes (5)
Evolution of antibody titers
Follow up every 2 months (month 0, 2, 4 and 6) until the end of the trial will be done to assess the evolution of P. vivax antibody titers.
Measured: At months 0, 2, 4 and 6 of the trial
Specific cytokine induction
Specific cytokine induction will be measured by IFN- γ, TNF-α, IL-2; IL- 4, IL-6, IL-10
Measured: At months 0, 2, 4 and 6 of the trial
Changes on vaccine biological security
Changes on vaccine biological security will be measured by renal, hepatic and hematologic function and pregnancy test.
Measured: On the day next to immunization and 1 or 2 weeks before the next immunization
Antibody functionality in vitro through inhibition of sporozoite invasion (ISI) to Hep-G2 cells.
Antibody functionality will be tested in vitro through essays of inhibition of sporozoite invasion (ISI) to Hep-G2 cells.
Measured: Every 2 months
Vaccine-induced protection for P. vivax
Vaccine-induced protection for P. vivax will be assessed by pre-patent period onset after infected mosquito bites exposure
Measured: 28 days after mosquito bites
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2014 (estimated)
- Study startAug 2014
- Primary completionSep 2015
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Malaria Vaccine and Drug Development Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Administrative Department of Science, Technology and Innovation, Colciencias
- Responsible party
- Principal investigator, Socrates Herrera Valencia, Malaria Vaccine and Drug Development Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02083068
- Sponsor's protocol ID
- 2304-493-26202
- Status last verified
- Mar 2018
- First submitted
- 5 Mar 2014
- Last updated
- 23 Mar 2018
- 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 21292872Arevalo-Herrera M, Gaitan X, Larmat-Delgado M, Caicedo MA, Herrera SM, Henao-Giraldo J, Castellanos A, Devaud JC, Pannatier A, Onate J, Corradin G, Herrera S. Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine. Nat Commun. 2022 Mar 25;13(1):1603. doi: 10.1038/s41467-022-29226-3.
PubMed 35338131
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Protective Efficacy of a Vaccine Derived From the Synthetic CS Protein of Plasmodium Vivax
- ClinicalTrials.gov ID
- NCT02083068
- Acronym / sponsor ID
- 2304-493-26202
- Conditions
- Malaria
- Keywords
- Malaria, vaccine, P. vivax
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Malaria Vaccine and Drug Development CenterUniversity, hospital or other
- Collaborators
- The Administrative Department of Science, Technology and Innovation, Colciencias
- Study start
- Aug 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 11 Mar 2014 (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 randomized, double-blind, controlled, which seeks to compare two groups of volunteers (naive and previously exposed to malaria) who were made 3 immunizations with a synthetic derivative of the CS protein of Plasmodium vivax in order to determine their protective efficacy. Then volunteers will be subject to an infectious challenge to assess the infectivity of gametocytes in the blood early stage of P. vivax in Anopheles albimanus mosquitoes.
Detailed description
This study is a prospective controlled, blinded clinical trial, designed to establish the protective efficacy induced by the vaccine PvCSP 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 immunization: Two other groups of volunteers will be immunized with the vaccine PvCSP. A group of 16 people without previous exposure to malaria (naive) and another 16 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 immunization stage 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.
Immunization: Volunteers will be immunized with the vaccine (n=16) or placebo (n=16).
Follow Up Volunteers will be under medical vigilance during the first hour following the immunization to detect any adverse reaction. After the first hour period a medical exam will be made. Eight hours after immunization, each volunteer will be telephoned to assess physical condition. Any adverse event (AE) will be registered.
Subsequent follow up will be made on the day next to immunization and 1 or 2 weeks before the next immunization by a new clinical evaluation and AE report. Volunteers will be educated to contact the research staff at any moment.
Infection of volunteers Immunized volunteers will be challenged on day ~150 of the study, 1 month after the third immunization by the bite of 3±1 infected mosquitos. 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.
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
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Biological: Vaccine PvCS N+C+R, Biological: Vaccine PvCS N+C10 individuals per sub- group to be immunized with the Vaccine PvCS N+C at month 0 and the Vaccine PvCS N+C+R at months 2 and 6 |
| Control | Placebo comparator | Biological: SSN Montanide ISA-51six individuals for each sub- group to be immunized with placebo SSN Montanide ISA-51 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Naïve group
- Healthy men and women aged 18-45 years. Signing freely and voluntary informed consent , accompanied by two witnesses who also sign.
- Not have a history of malaria infection. For women, use of adequate contraception from the star restriction to be lifted by a doctor for contraception study. Accept not to travel to areas considered endemic for malaria during Trophies infectious period (1 month ) ( Buenaventura , Tierralta , Pretoria , Tumaco ,Urabá and Bajo Cauca) .
- Be reachable by phone throughout the study period. Being Duffy positive ( Fy +) . Levels of hemoglobin ( Hb) > 11 g / dl. Availability to participate during the period in which they develop the study. Do not be participating in another clinical study
- 2. Preimmune group
Key exclusion criteria (5 listed)
- Step 1
- Step 2 Patients that have chronic or acute disease, different from malaria by P. vivax.
- Having a history of disease or clinical conditions that according to medical criteria might increase significantly the risk related with participation on this study Hemoglobin levels <9 g/dL at the time of recruitment Have received antimalarial treatment before the diagnosis
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 |
|---|---|---|
| Vaccine PvCS N+C+RVaccine PvCS N+C+R 60 mcg, freeze dried powder, Batch n°P0RGB, Exp: 18.10.2015 At month 2 and 6 | Biological | Experimental |
| Vaccine PvCS N+CVaccine PvCS N+C 60 mcg, freeze dried powder, Batch n°P0RGA, Exp: 18.10.2015, at month 0 | Biological | Experimental |
| SSN Montanide ISA-51SSN Montanide ISA-51 1 mL | Biological | Control |
Primary outcome
Protective efficacy against P. vivax infection on volunteers exposed to infected mosquito bites
Time frame: Thirty days after the last immunization
Vaccine protective efficacy against P. vivax infection on volunteers exposed to infected mosquito bites
5 secondary outcomes
Evolution of antibody titers
Time frame: At months 0, 2, 4 and 6 of the trial
Specific cytokine induction
Time frame: At months 0, 2, 4 and 6 of the trial
Changes on vaccine biological security
Time frame: On the day next to immunization and 1 or 2 weeks before the next immunization
Antibody functionality in vitro through inhibition of sporozoite invasion (ISI) to Hep-G2 cells.
Time frame: Every 2 months
Vaccine-induced protection for P. vivax
Time frame: 28 days after mosquito bites
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 23 Mar 2018.
- 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.
- Derived from this study: PubMed 35338131Arevalo-Herrera M, Gaitan X, Larmat-Delgado M, Caicedo MA, Herrera SM, Henao-Giraldo J, Castellanos A, Devaud JC, Pannatier A, Onate J, Corradin G, Herrera S. Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine. Nat Commun. 2022 Mar 25;13(1):1603. doi: 10.1038/s41467-022-29226-3.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vaccine PvCS N+C+R, Vaccine PvCS N+C and SSN Montanide ISA-51 in people with Malaria, run by Malaria Vaccine and Drug Development Center 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 5 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 23 Mar 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 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. Some participants in this study may receive a placebo. 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 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?
Protective efficacy against P. vivax infection on volunteers exposed to infected mosquito bites (time frame: Thirty days after the last immunization). 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 NCT02083068, which also lists 2 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 23 Mar 2018.