rCSP/AP10-602 [GLA-LSQ] Vaccine Trial
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a study to evaluate the safety, immunogenicity, and efficacy of a recombinant
      circumsporozoite protein (rCSP) malaria vaccine administered with and without AP 10-602
      [Glucopyranosyl Lipid A (GLA) in liposome Quillaja saponaria 21 formulation (LSQ)] adjuvant.
      59 healthy adult, malaria naive volunteers aged 18 to 45 will receive vaccination with or
      without adjuvant (10 of those volunteers will receive rCSP alone) in five dose escalating
      groups. Each group will receive 3 vaccination doses total, with intramuscular (IM) injections
      on days 1, 29, and 85. A sixth group of 6 volunteers will receive no vaccinations and will
      participate as a control in a Controlled Human Malaria Infection (CHMI) challenge with two of
      the vaccinated groups. The study will be conducted at the Center for Vaccine Development
      (CVD) in Baltimore, Maryland. The patient participation duration is expected to be up to 886
      days (up to 117 days for nonvaccination group). This study will test two hypotheses: (1) the
      rCSP/AP 10-602 [GLA-LSQ] candidate malaria vaccine will induce an immune response in a
      dose-dependent manner as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP
      10-602 [GLA-LSQ] candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines
      compared to unvaccinated infectivity controls. The primary objective is to assess the safety
      and reactogenicity of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered
      intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 490 day
      schedule (Group 4) to healthy malaria-naive adults aged 18-45 years.
    

Detailed description: 
      This is a phase I, single-site, dose escalation study to evaluate the safety, immunogenicity,
      and efficacy of the recombinant circumsporozoite protein (rCSP) antigen malaria vaccine
      administered with and without AP 10-602 [Glucopyranosyl Lipid A (GLA) in liposome Quillaja
      saponaria 21 formulation (LSQ)]. The study population will consist of 65 healthy male and
      female adults aged 18 to 45 years old and be conducted at the Center for Vaccine Development
      (CVD) in Baltimore, Maryland. 49 healthy, malaria-naïve volunteers will receive rCSP
      vaccination with AP 10-602 [GLA-LSQ] adjuvant. Ten volunteers will receive rCSP alone. Each
      dose-escalating group will receive 3 intramuscular (IM) total doses of vaccine on days 1, 29,
      and 85. Group 1 will receive a dose of 10 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg
      LSQ) at each injection; Group 2 will receive 30 mcg rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2
      mcg LSQ); Group 3 will receive 30 mcg rCSP without adjuvant; and Group 4 will receive 60 mcg
      rCSP + AP 10-602 [GLA-LSQ] (5 mcg GLA - 2 mcg LSQ). The dose for Group 5 will depend on
      immunogenicity analysis from groups 1, 2 and 3. If immunogenicity analysis conducted 28 days
      post-2nd dose in Groups 1, 2 and 3 show promise (at least fourfold increase in geometric mean
      anti-CSP antibody or geometric mean anti-CSP titer of 20), the 10 volunteers in Group 5 will
      receive the lowest rCSP dose that gives this predefined immunogenic response ((either 10 or
      30 mcg rCSP) + AP 10-602 [GLA-LSQ],]), otherwise, Group 5 will receive 60 mcg rCSP + AP
      10-602 [GLA-LSQ]. Groups will be vaccinated in a stepwise manner following a "telescoped"
      design. A sixth group of 6 volunteers (Group 6) will receive no vaccinations and will be used
      as an infectivity control for a Controlled Human Malaria Infection (CHMI) challenge. Groups 4
      and 5 will also undergo the CHMI challenge together, 28 days after the last vaccination. The
      patient participation duration is expected to be up to 886 days for Groups 1, 2, 3, 4, and 5;
      and up to 117 days for Group 6. This study will test two hypotheses: (1) the rCSP/AP 10-602
      [GLA-LSQ] candidate malaria vaccine will induce an immune response in a dose-dependent manner
      as measured by anti-CSP antibody titer via ELISA and (2) the rCSP/AP 10-602 [GLA-LSQ]
      candidate malaria vaccine will provide a minimum of 50% efficacy in vaccines compared to
      unvaccinated infectivity controls. The primary objective is to assess the safety and
      reactogenicity of candidate rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when administered
      intramuscularly on a 1, 29, and 85 day schedule (Groups 1-3, 4B, 5) and on a 1 and 461 day
      schedule (Group 4) to healthy malaria-naive adults aged 18-45 years. The secondary objectives
      are to (1) assess immunogenicity of rCSP/AP 10-602 [GLA-LSQ] malaria vaccine when
      administered intramuscularly on a 1, 29, and 85 day (Groups 1-3, 4B, 5) and on a 1 and 490
      day schedule (Group 4) schedule and (2) to assess the preliminary efficacy of candidate
      rCSP/AP 10-602 [GLA-LSQ] malaria vaccine against infection with Plasmodium falciparum malaria
      (defined as P. falciparum asexual parasitemia or a delay in patency of infection > 2 days
      versus unimmunized infectivity controls) under Controlled Human Malaria Infection (CHMI).
    

Intervention name(s): AP10-602; Malaria challenge; rCSP
Intervention type(s): Other; Other; Biological
Intervention description(s): Glucopyranosyl Lipid A -liposome-Quillaja Saponaria 21 (GLA-LSQ).; Exposure to mosquitoes infected with P. falciparum.; The rCSP malaria vaccine is a recombinant full-length P. falciparum circumsporozoite protein comprised of an amino terminus that binds heparin-sulfate proteoglycans, a four-amino-acid repeat region and a carboxy-terminus that contains a thrombospondin-like Type I region domain.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: AP 10-602 [GLA-LSQ]; Challenge; Healthy adults; Malaria; P. falciparum; rCSP; Vaccine