Safety, Tolerability, and Immunogenicity of the Vaccine Candidates ID93 + AP10-602 and ID93 + GLA-SE Administered Intramuscularly in Healthy Adult Subjects
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I randomized, double blind clinical trial designed to evaluate the safety,
      tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated
      with GLA-SE or AP10-602 adjuvant in 70 healthy adults 18-49 years of age. Subjects will
      receive a total of 3 doses administered intramuscularly on Days 1, 29 and 57. Subjects will
      be monitored for approximately 422 days (365 days following the third study injection),
      including safety laboratory analyses done just prior to and 7 days following each study
      injection. Blood samples will be obtained for immunological assays (Luminex, intracellular
      cytokine staining at Days 1 and 71, and antibody analysis at Days 1 and 85). The primary
      objective is to evaluate the safety and tolerability of 10 µg ID93 + 5 or 10 µg AP10-602
      compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone following three consecutive
      intramuscular injections administered on Days 1, 29 and 57.
    

Detailed description: 
      TB causes significant morbidity and mortality throughout the world. Strains of Mtb are
      becoming increasingly resistant to antimycobacterial drugs and therapy is often associated
      with poor compliance, which increases the likelihood of antimicrobial resistance. The current
      licensed BCG vaccine does not prevent reactivation or reinfection in adults so there is a
      great need for a more effective vaccine. ID93 is a recombinant antigen that, when mixed with
      the adjuvants GLA-SE and AP10-602, shows great promise in eliciting what is thought to be an
      important Th1 T cell response and limits the bacterial burden in Mtb challenged animals. This
      study is a phase I randomized, double blind clinical trial designed to evaluate the safety,
      tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated
      with GLA-SE or AP10-602. This study will enroll 70 healthy males and non-pregnant females
      subjects, aged 18 to 49. Subjects who meet all eligibility criteria will be randomized to
      ID93 alone, ID93 + GLA-SE, or ID93 + AP10-602 at either dose level. Study injections will be
      performed and subjects will be observed in clinic for 30 minutes. All subjects will complete
      a written subject memory aid that solicits local and systemic reactogenicity adverse events
      for 7 days following each study injection. After subjects are reevaluated to ensure they
      continue to meet eligibility criteria they will undergo second and third study injections on
      Days 29 and 57. General safety will be evaluated on Days 1, 3, 8, 29, 31, 36, 57, 59, 64, 71,
      85, 169, and 422 for each subject. The occurrence of serious adverse events and the new onset
      of any adverse events of special interest (AESI) will be collected throughout the study
      period (approximately 422 days). Each subject's duration of participation will be about 15
      months. The Primary Objective is : To evaluate the safety and tolerability of 10 µg ID93 + 5
      or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone following three
      consecutive intramuscular injections administered on Days 1, 29 and 57. The Secondary
      Objective is: To assess the immunogenicity of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10
      µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone by quantifying T cell responses and IgG antibody
      responses to ID93 at specified time points.
    

Intervention name(s): AP10-602; GLA-SE; ID93
Intervention type(s): Other; Biological; Biological
Intervention description(s): AP10-602 contains GLA formulated with liposomes and an additional immunological adjuvant. The ID93 (10 mcg) + AP10-602 (5 mcg) arm will receive intervention on days 1, 29 and 57. The ID93 (10 mcg) + AP10-602 (10 mcg) arm will receive intervention on days 1, 29 and 57.; Glucopyranosyl Lipid A- Stable oil-in-water emulsion (GLA-SE). The ID93 (10 mcg) + GLA-SE (5 mcg) arm will receive intervention on days 1, 29 and 57; ID93 is a fusion polyprotein comprising four Mtb antigens (Rv2608, Rv3619, Rv3620, Rv1813). All arms will receive 10 mcg ID93 IM on days 1, 29 and 57
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: adjuvants; AP10-602; GLA-SE; ID93; Tuberculosis; vaccine