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Malaria, VivaxEarly Phase 1ChallengeIINCT01083095

Establishment of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers

A Early Phase 1 study testing Sporozoite Challenge Model for Plasmodium vivax in Humans in people with Malaria, Vivax, run by Malaria Vaccine and Drug Development Center at 1 site in Colombia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A clinical trial aimed to standardize a vivax sporozoite infection model in human volunteers was conducted at the Malaria Vaccine and Drug Development Center (MVDC) in collaboration with the Immunology Institute at Valle State University and the Fundación Clínica Valle del Lili (FCVL) in Cali, Colombia. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Malaria, Vivax
What is being tested?
Sporozoite Challenge Model for Plasmodium vivax in Humans
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteColombia
Study dates
Jan 2005to Dec 2006
Phase
Early 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 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy male or non-pregnant female adults (18- 50 years of age).
  • Use of adequate contraceptive method from the initiation of the study until two months after sporozoite challenge for females.
  • No plans to travel to a malaria endemic area during the course of the study and agree to not travel outside the study area from Day 7 to Day 23 post-challenge (the high risk period for becoming parasitemic).
  • Reachable by phone during the entire study period
  • Duffy positive phenotype

Who cannot join

  • Are <18 or >49 years of age.
  • Any female who is pregnant at serum positive B-HCG screening or who is nursing.
  • Duffy negative phenotype.
  • G-6-PD deficiency or any other hemoglobinopathy.
  • Current or past infection with any species of malaria
  • History of allergy to antimalarial drugs or immediate type hypersensitivity reactions to mosquito bites.
Show all 10Show fewer
  • Clinical or laboratory evidence of significant systemic disease, including hepatic, renal, cardiac, immunologic or hematological disease. Are HIV positive or have any other known immunodeficiency (including receiving immunosuppressive therapy or a history of splenectomy); are infected with hepatitis B or C virus; have a history of autoimmune disease (including inflammatory bowel disease, hemolytic anemia, autoimmune hepatitis, rheumatoid arthritis, lupus, etc.) or connective tissue disease or have any other serious underlying medical condition.
  • Clinically significant laboratory abnormalities as determined by the Investigator(s).
  • Plan to have surgery between enrollment and the end of the challenge follow-up.
  • Have any other conditions that are determined by at least two concurring investigators that may interfere with the capacity to provide free and willing informed consent.

Trial locations and contacts

1 site in 1 country.

Colombia1 site
  • Malaria Vaccine and Drug Testing Center

    Cali, Valle del Cauca Department

Other trials in Colombia

About this study

A clinical trial aimed to standardize a vivax sporozoite infection model in human volunteers was conducted at the Malaria Vaccine and Drug Development Center (MVDC) in collaboration with the Immunology Institute at Valle State University and the Fundación Clínica Valle del Lili (FCVL) in Cali, Colombia.

The primary objective was to determine if naïve human volunteers could be safely and reproducibly infected by the bite of An. albimanus mosquitoes carrying P. vivax sporozoites in their salivary glands and a secondary objective consisted in determining the minimal number of infected mosquitoes required to infect all volunteers, with a reproducible pre-patent period.

The trial was divided into two steps: Step A directed to obtain human blood infected with P.vivax parasite used to infect anopheles mosquitoes and Step B to produce P. vivax sporozoites in Anopheles mosquitoes to determine the dose response of naive human volunteers exposed to 3 +/- 1, 6 +/- 1 y 9 +/- 1 mosquitoes bites. A total of 15 samples of P. vivax infected donors were used to infect different batches of mosquitoes.

Read the detailed description

Study design:

The study was a randomized open label clinical trial to establish a sporozoite challenge model for Plasmodium vivax in humans. The development and standardization of such a model will make it possible to evaluate the efficacy of candidate P. vivax vaccines in Phase 2a trials. The study is divided into two successive steps:

Step A Parasite Blood Donation: Volunteers were recruited passively from a group of patients who presented with active P. vivax infection and accepted to donate infected blood. Samples of P. vivax infected blood was collected and was screened for infectious diseases, according to standard blood bank procedures. Colonized Anopheles albimanus mosquitoes were fed with this blood using a Membrane Feeding Assay (MFA). Sixteen (16) days after, selected positive mosquito batches were used for step B.

Step B Challenge: After informed consent signature, a total of 18 healthy volunteers were randomly allocated to Groups 1, 2 and 3, of 6 volunteers each and were challenged with the bite of 3±1, 6±1 or 9±1 P. vivax infected mosquitoes. Volunteers were closely monitored post infection, and were treated as soon as blood infection becomes patent as ascertained by microscopic examination of thick blood smears (TBS). Comparison of three bite patterns was used to select the optimal number of P. vivax-infected mosquito bites needed to provide reliable and reproducible blood infection.

Infection was expected to occur in the first 30 days. After that time, if infection was not documented, antimalarial treatment was planned. Nevertheless all exposed volunteers presented malarial infection. Despite infection was expected before day 30, a 18 month follow-up was performed with to be sure no delay malaria infection presented without detection. So, the total duration of the study was 18 months.

Infection was determined by the detection of P. vivax parasites on TBS from volunteers included.

Eligibility criteria for Blood donors Step A were:

  • Adult, male or female (18-60 years of age).
  • Capacity to freely understand and sign an informed consent form of participation.
  • TBS Positive for P.vivax but negative for all other malaria species.
  • P.vivax gametocytemia > 0.2%.

Exclusion criteria

  • Unable to provide free and willing written informed consent.
  • Have or have had any illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the blood donation.

Eligibility and exclusion criteria for Challenge is described below in this format.

Close monitoring of adverse events was performed, both by medical examination as by telephone contact.

Conditions
Malaria, Vivax
Being tested
Sporozoite Challenge Model for Plasmodium vivax in Humans
Keywords
Malaria, Sporozoite, Challenge Model, Plasmodium vivax, Human Volunteers
Medical subject headings
Malaria, Vivax, Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sporozoite Challenge Model for Plasmodium vivax in HumansBiological

    Also called Controlled malaria vivax infection challenge

    Eighteen naïve volunteers were exposed to the bite of carrying P. vivax sporozoites. Volunteers were randomly allocated to 1 of 6 groups and exposed to different numbers of mosquito biting, for 10 min. After feeding, dissection of all mosquitoes exposed in the cage was performed, to confirm the presence of a blood meal in their midguts and sporozoites in their salivary glands. If a volunteer did not get the number of infective bites assigned for his/her group, he/she was allowed to be bitten for a new group of mosquitoes until a total of 3±1, 6±1, or 9±1 mosquito bites were achieved.

Study groups in NCT01083095
Study groupRoleWhat they receive
3 +/- 1 biteActive comparatorVolunteers were exposed to mosquito biting for 10 min
Receives: Biological: Sporozoite Challenge Model for Plasmodium vivax in Humans
6 +/- 1 biteActive comparatorVolunteers were exposed to mosquito biting for 10 min
Receives: Biological: Sporozoite Challenge Model for Plasmodium vivax in Humans
9 +/- 1 biteActive comparatorVolunteers were exposed to mosquito biting for 15 min
Receives: Biological: Sporozoite Challenge Model for Plasmodium vivax in Humans

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of infected naïve human volunteers after different number of infected mosquito biting

    Measured: 30 days

Secondary outcomes (1)
  1. Minimal number of infected mosquitoes required to infect all volunteers with a reproducible prepatent period

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2010 (estimated)
  2. Study startJan 2005
  3. Primary completionMar 2005
  4. Study completionDec 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01083095
Sponsor's protocol ID
MVDC-2003-003
Other IDs
Reto II
Acronym
ChallengeII
Status last verified
Dec 2006
First submitted
6 Mar 2010
Last updated
9 Mar 2010
Results posted
No
Data monitoring committee
Yes

Publications

  • Clyde DF, Most H, McCarthy VC, Vanderberg JP. Immunization of man against sporozite-induced falciparum malaria. Am J Med Sci. 1973 Sep;266(3):169-77. doi: 10.1097/00000441-197309000-00002. No abstract available.

    PubMed 4583408
  • Good MF, Pombo D, Quakyi IA, Riley EM, Houghten RA, Menon A, Alling DW, Berzofsky JA, Miller LH. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1199-203. doi: 10.1073/pnas.85.4.1199.

    PubMed 2448793
  • Herrera MA, de Plata C, Gonzalez JM, Corradin G, Herrera S. Immunogenicity of multiple antigen peptides containing Plasmodium vivax CS epitopes in BALB/c mice. Mem Inst Oswaldo Cruz. 1994;89 Suppl 2:71-6. doi: 10.1590/s0074-02761994000600017.

    PubMed 7565136
  • Arevalo-Herrera M, Herrera S. Plasmodium vivax malaria vaccine development. Mol Immunol. 2001 Dec;38(6):443-55. doi: 10.1016/s0161-5890(01)00080-3.

    PubMed 11741694
  • Arevalo-Herrera M, Roggero MA, Gonzalez JM, Vergara J, Corradin G, Lopez JA, Herrera S. Mapping and comparison of the B-cell epitopes recognized on the Plasmodium vivax circumsporozoite protein by immune Colombians and immunized Aotus monkeys. Ann Trop Med Parasitol. 1998 Jul;92(5):539-51.

    PubMed 9797827
  • Baird JK, Tiwari T, Martin GJ, Tamminga CL, Prout TM, Tjaden J, Bravet PP, Rawlins S, Ferrel M, Carucci D, Hoffman SL. Chloroquine for the treatment of uncomplicated malaria in Guyana. Ann Trop Med Parasitol. 2002 Jun;96(4):339-48. doi: 10.1179/000349802125001023.

    PubMed 12171615
  • Blair S, Lopez ML, Pineros JG, Alvarez T, Tobon A, Carmona J. [Therapeutic efficacy of 3 treatment protocols for non-complicated Plasmodium falciparum malaria, Antioquia, Colombia, 2002]. Biomedica. 2003 Sep;23(3):318-27. Spanish.

    PubMed 14582335
  • Chotivanich K, Silamut K, Udomsangpetch R, Stepniewska KA, Pukrittayakamee S, Looareesuwan S, White NJ. Ex-vivo short-term culture and developmental assessment of Plasmodium vivax. Trans R Soc Trop Med Hyg. 2001 Nov-Dec;95(6):677-80. doi: 10.1016/s0035-9203(01)90113-0.

    PubMed 11816444
  • Chulay JD, Schneider I, Cosgriff TM, Hoffman SL, Ballou WR, Quakyi IA, Carter R, Trosper JH, Hockmeyer WT. Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. Am J Trop Med Hyg. 1986 Jan;35(1):66-8. doi: 10.4269/ajtmh.1986.35.66.

    PubMed 3511753
  • Church LW, Le TP, Bryan JP, Gordon DM, Edelman R, Fries L, Davis JR, Herrington DA, Clyde DF, Shmuklarsky MJ, Schneider I, McGovern TW, Chulay JD, Ballou WR, Hoffman SL. Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. J Infect Dis. 1997 Apr;175(4):915-20. doi: 10.1086/513990.

    PubMed 9086149
  • Clyde DF, McCarthy VC, Miller RM, Hornick RB. Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am J Med Sci. 1973 Dec;266(6):398-403. doi: 10.1097/00000441-197312000-00001. No abstract available.

    PubMed 4590095
  • Clyde DF. Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am J Trop Med Hyg. 1975 May;24(3):397-401. doi: 10.4269/ajtmh.1975.24.397.

    PubMed 808142
  • Clyde DF. Immunity to falciparum and vivax malaria induced by irradiated sporozoites: a review of the University of Maryland studies, 1971-75. Bull World Health Organ. 1990;68 Suppl(Suppl):9-12.

    PubMed 2094597
  • Collins WE, Jeffery GM. Primaquine resistance in Plasmodium vivax. Am J Trop Med Hyg. 1996 Sep;55(3):243-9. doi: 10.4269/ajtmh.1996.55.243.

    PubMed 8842108
  • Danis M. [Therapeutic advances against malaria in 2003]. Med Trop (Mars). 2003;63(3):267-70. French.

    PubMed 14579464

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Sporozoite Challenge Model for Plasmodium vivax in Humans in people with Malaria, Vivax, 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 5 inclusion and 10 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 9 Mar 2010. 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 phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

Percentage of infected naïve human volunteers after different number of infected mosquito biting (time frame: 30 days). 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 NCT01083095, which also lists 27 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 9 Mar 2010.

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