Proof-of-Concept Study of MSP3-LSP Vaccine to Protect Against Malaria in Africa
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2

Summary: 
      Hypothesis: The MSP3-LSP/Alum vaccine, administered to children will have a protective
      efficacy of at least 30% (lower bound of confidence interval of 0) against malaria disease
      occurring during a period beginning from 14 days after the 3rd immunization until 1 year
      after.

      The primary objective of this double-blind, randomized, controlled trial will be to assess
      the clinical efficacy of MSP3-LSP/AlOH vaccine when administered by subcutaneous route in
      children aged 12-48 months against all clinical malaria episodes occurring during a period
      beginning from 14 days after the 3rd immunization until 3 months after 3rd immunization, when
      administered according to the following schedule:- Primary administration: Three doses of
      administered 4 weeks apart

      Secondary administration (Boost): One dose 3 months after the third dose in year 1 of the
      trial; and two doses, given exactly one year after the date corresponding to the third dose
      and the first boost given during Year 1

      Case definition for an episode of malaria is a febrile illness with axillary temperature of ≥
      37.5ºC with P. falciparum parasitemia ≥ 5000 per μL
    

Detailed description: 
      This is a Phase 2 b, randomized, controlled trial, comparing MSP3-LSP experimental malaria
      vaccine with the comparator Verorab rabies vaccine (primary series) and normal saline
      (secondary/booster series). The trial is being conducted in two sites, Doneguebougou and
      surroundings (Koulikoro) and Bougoula Hameau and surroundings (Sikasso).

      Each site will enroll 400 subjects. Subjects aged 12-48 months will be enrolled and
      randomized in a 1:1 ratio to receive either 30 µg of MSP3-LSP/AlOH in 0.5 mL or the control
      vaccine, Verorab Rabies subcutaneously.

      The primary series of vaccinations will be given on days 0, 28 and 56. The first of the
      secondary/booster series will be administered 3 months after completing the primary series
      (D146) in Year 1, and the subsequent booster doses will be administered one year after the
      3rd dose (D416) and one year after the first booster dose (D506) in Year 2.

      For safety, occurrence of adverse events will be solicited during daily home visit by field
      workers for 6 days after each vaccination. Unsolicited adverse events will be documented for
      the following 28 days after each dose.

      For efficacy, suspect cases will be detected through weekly home visits following the 1st
      vaccination and continuing throughout the duration of the trial.

      In addition to active case detection through home visits, parents and care-givers of the
      subjects will be advised of signs and symptom of illness and instructed to bring sick
      children to the on-site clinic for assessment and treatment. Study clinical staff will be
      available round-the clock for the entire duration of the trial. During these unscheduled
      visits malaria smears, blood paper filter and hemoglobin will be done in case of signs or
      symptoms compatible with clinical malaria.

      Children will be followed for two years following the first vaccination. Clinic visits are
      scheduled throughout the follow-up period for clinical assessment, malaria smear, blood paper
      filter and hemoglobin systematically on days 0, 28, 56, 86, 116, 146, 180, 236, 326, 416,
      446, 506, 536 and 730. The humoral immune response to the vaccine antigen will be assessed
      using ELISA on days 0, 28, 56, 86, 116, 146, 180, 236, 416, 446, 506, and 730. Cellular
      immune responses to the vaccine antigens (MSP3-LSP and peptides a,b,c,d) will be assessed on
      days 0, 86,146, and 416 using CBA on a subset of 50 MSP3 vaccinated individuals. The
      functionality of the induced immune responses using Western Blot (WB) method and ADCI
      technique will be evaluated at screening and on days 86, 146, 236, 416, 506 and 730.
    

Intervention name(s): MSP3-LSP/AlOH; Verorab Vaccine; 0.9% NaCl/Normal Saline
Intervention type(s): Biological; Biological; Other
Intervention description(s): 30 µg of test vaccine MSP3-LSP/AlOH, administered by subcutaneous route according to the following schedule:- Primary administration: Three doses administered at 4 weeks interval: D0, D28 (± 2 days), D56 (± 4 days)
Secondary administration (Boost):
Year 1: One dose 3 months after the third dose Year 2: Two doses, given exactly one year after the date corresponding to the third dose and the first boost given during Year 1; The Verorab rabies vaccine will be given as control for the primary series of the experimental vaccine. It consists of inactivated rabies virus produced in vero cells (Wistar Rabies PM/W138 1503-3M (inactivated). Manufacturer SANOFI PASTEUR SA. Presentation is 0.5 ml per dose in a pre-filled syringe.; 0.5 ml per dose; to be given as control for the secondary/booster doses of experimental vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: malaria; vaccine; clinical trials; proof of concept; efficacy