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临床试验/NCT04739917
NCT04739917Unknown2 期

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

Malaria Vaccine and Drug Development Center1 个研究点 分布在 1 个国家目标入组 120 人开始时间: 2021年6月1日最近更新:
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适应症

试验速览

阶段
2 期
入组人数
120
试验地点
1
主要终点
Frequency of first case of P. vivax malaria after CHMI and meeting the primary case definition.
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Prevention
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
18 Years 至 45 Years（Adult）
性别
All
接受健康志愿者
是

入选标准

  • •Naïve group:
  • •Non-pregnant, healthy men and women between 18-45 years old.
  • •Freely and voluntarily sign an IC, accompanied by two witnesses who must also sign.
  • •Absence history of malaria infection.
  • •To have negative serology for the PvCS protein by the ELISA test.
  • •For women, not be pregnant.
  • •Use of an adequate contraceptive method from the beginning until the contraceptive restriction is lifted by a study doctor, at the end of the study.
  • •To accept not to travel to areas considered as endemic for malaria from the infectious challenge period and to the end of its follow-up (1 month).
  • •Be reachable by phone throughout the study period.
  • •To be Duffy positive (Fy +).
  • •Have Hemoglobin (Hb) levels> 11 g / dl.
  • •Be willing to participate during the period in which the study will take place.
  • •Not be participating in another clinical study.
  • •Be affiliated with the general health social security system of Colombia, in any of its regimes (subsidized or contributory)
  • •Semi-immune group:
  • •Non-pregnant, healthy men and women between 18-45 years old,
  • •Freely and voluntarily sign an informed consent, accompanied by two witnesses who will also sign.
  • •Have a history of malaria infection (s) and positive serological tests (ELISA) for P. vivax.
  • •For women, not be pregnant or nursing.
  • •For women, use of adequate contraception from inception until the contraceptive restriction is lifted by a study physician.
  • •Be a permanent resident of the municipality of Quibdó during the study.
  • •Be reachable by phone throughout the study period.
  • •Availability to participate during the period in which the study will take place.
  • •Be affiliated with the general health social security system of Colombia, in any of its regimes (subsidized or contributory)

排除标准

  • •Naïve group:
  • •Glucose 6 phosphate dehydrogenase deficiency (G-6-P-D).
  • •Present any hemoglobinopathy (eg HbS).
  • •Personal history of allergies to medications or insect bites.
  • •Have received vaccination against malaria.
  • •Clinical or laboratory abnormalities determined by the investigator (s).
  • •IFAT> 1:20 for P. vivax in screening tests.
  • •Have lived in a malaria-endemic region during the 12 months before the study.
  • •Clinical or laboratory evidence of systemic disease, including kidney, liver, cardiovascular, pulmonary, psychiatric, or other diseases that may negatively impact and alter study results.
  • •Evidence of active hepatitis B or Hepatitis C infection
  • •Evidence of active HIV infection.
  • •History of transfusion of any blood product in the 6 (six) months before the study.
  • •Plan to have surgery from the recruitment period to the end of the post-challenge follow-ups.
  • •Presence or history of autoimmune disease (lupus, rheumatoid arthritis, thyroiditis, or other).
  • •Splenectomized volunteers.
  • •Volunteers in treatment with drugs with activity on the immune system (steroids, immunosuppressive agents, or immunomodulators).
  • •History of alcoholism or drug abuse defined as a habit that interferes with the normal social functioning of the individual.
  • •Any condition that may interfere with the ability to provide a free and voluntary IC.
  • •Not being affiliated with the general health social security system of Colombia, in any of its regimes (subsidized or contributory)
  • •Semi-immune group:
  • •IFAT negative (<1:20) for P. vivax in screening tests.
  • •The other criteria used in the case of naïve volunteers, except the antecedent of having lived in the endemic area.

结局指标

主要结局

Frequency of first case of P. vivax malaria after CHMI and meeting the primary case definition.

时间窗: Assessed over average of 16-18 days post CHMI (range 7 to 60 days)

The first case of malaria meeting the primary case definition will be defined as the first or only episodes with the presence of Plasmodium vivax parasitemia ≥ 0.1% by thick blood smear and malaria qPCR.

次要结局

  • T-cell response measurement - Bioplex(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Characterization of T lymphocytes(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Characterization of B lymphocytes.(Days 0, 30, 60, 90, 120, 180, 210 and 240)
  • Characterization of monocytes(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Antibody functionality in vitro through inhibition of sporozoite invasion (ISI) to Hep-G2 cells.(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Vaccine-induced protection for P. vivax(Thirty days after mosquito bite challenge (Controlled Human Malaria Infection))
  • Concentration of specific anti-PvCS IgG antibodies IgG (isotypes) against the different functional fragments of the Pv-CS protein.(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Specific cytokine induction(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • T-cell response measurement - Flow cytometry(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • T-cell response measurement - ELIspot(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Multiomics testing (i.e., transcriptomics, genomics)(Days 0, 30, 90, 195 and 225.)
  • Safety - Number of Subjects With Any and Grade 3 Solicited Local Symptoms(During the 7-day (Days 0-6) post-vaccination period following each dose and across doses)
  • Safety - Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(During the 7-day (Days 0-6) post-vaccination period following each dose and across doses)
  • Safety - Number of Subjects With Aspartate aminotransferase (AST) Values Outside Normal Ranges With Toxicity(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Prothrombin time (PT)) Values Outside Normal Ranges With Toxicity(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Partial thromboplastin time (PTT) Values Outside Normal Ranges With Toxicity(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Any Unsolicited Adverse Events (AEs)(Within the 30-day (Days 0-29) post-vaccination follow-up period)
  • Safety - Number of Subjects With Serious Adverse Events (SAEs)(Throughout the study period (Day 0 - Month 14))
  • Safety - Number of Subjects With Hemoglobin Values Outside Normal Ranges With Toxicity Grades(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With White Blood Cell (WBC) Values Outside Normal Ranges With Toxicity Grades(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Platelet Values Outside Normal Ranges With Toxicity Grades(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Alanine Aminotransferase (ALT) Values Outside Normal Ranges With Toxicity Grades(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Creatinine Values Outside Normal Ranges With Toxicity Grades(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Bilirubin Values Outside Normal Ranges With Toxicity Grades(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Alkaline phosphatase Values Outside Normal Ranges With Toxicity(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of Subjects With Blood urea nitrogen (BUN) Values Outside Normal Ranges With Toxicity(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Number of participants with confirmed pregnancy(Days 0, 30, 60, 90, 120, 180, 210 and 240.)
  • Safety - Glucose-6-phosphate dehydrogenase deficiency(Day 0.)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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