NCT04739917

Efficacy of a Synthetic Vaccine Derived From Plasmodium Vivax Circumsporozoite Protein (PvCS) in naïve and Semi-immune Volunteers

Safety and Protective Efficacy of a Synthetic Vaccine Derived From the CS Protein of Plasmodium Vivax: a Double-blind, Placebo-controlled, Randomized Clinical Trial in naïve and Pre-immune Colombian Volunteers

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Malaria Vaccine and Drug Development Center · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This is a randomized, double-blind, controlled, which seeks to compare two groups of volunteers (naive and previously exposed to malaria) vaccinated with three doses of a synthetic derivative of the CS protein of Plasmodium vivax to determine their protective efficacy. Then volunteers will be subject to an infectious challenge (Controlled Human Malaria Infection) 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. Volunteers will be recruited in Cali, Colombia and Quibdó, Colombia. Study subjects: This study will require the involvement of two types of volunteers, parasite donors and volunteers for immunization 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 PvCSP vaccine. A group of 60 people without previous exposure to malaria (naïve) and another 60 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 mosquito's blood from donors will be used to feed three-day-old mosquitoes by artificial membrane feeding technique. At day 7, a sample of mosquitoes will be examined to determine the level of infection by dissection of the mosquito's gut. On day 14, a small number 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 (Colombia), non-endemic region, and in Quibdó (Colombia), a malaria endemic region, through various activities such as conferences, meetings and other strategies previously approved by the IRB, like posters, radio advertising flyers and social media. Immunization: Volunteers will be immunized with the vaccine (n=60) or placebo (n=60). Follow-up of volunteers will be performed 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 contacted via telephone 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 instructed 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 2-4 infected mosquito. A "feeding cage" will be placed on the forearm of a volunteer for 10 minutes, allowing that the feeding window, which will be covered by a mesh surface be placed against the volunteer's skin. Volunteers will be instructed 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 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 Health: chloroquine (three (3) doses: 600 mg initially, followed by 450 mg at 24, and 48 hours), associated with primaquine (30mg/day) 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, Vivax

Interventions

Type	Name	Description
BIOLOGICAL	Vaccine PvCS N+C+R 150 mcg	Vaccine PvCS N+C+R 150 mcg (Montanide ISA-51), freeze dried powder.
OTHER	Placebo SSN Montanide ISA-51 1 mL	SSN Montanide ISA-51 1 mL

Timeline

• Start date: 2021-06-01
• Primary completion: 2022-06-01
• Completion: 2022-12-01
• First posted: 2021-02-05
• Last updated: 2021-03-01

Locations

1 site across 1 country: Colombia