A Phase 2 Bridging Study to Assess the New Formulation of ETVAX
Condition: Healty Volunteers; Preventable Disease, Vaccine
MeSH terms: Vaccine-Preventable Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a phase 2,prospective double-blind, randomized, parallel-group study with the aim to
      demonstrate non-inferiority, in terms of immunogenicity, between the wet formulation and a
      newly developed partially dried formulation of selected components of ETVAX.
    

Detailed description: 
      This is a phase 2, prospective double-blind, randomized, parallel-group study with the aim to
      demonstrate non-inferiority, in terms of immunogenicity, between the wet formulation and a
      newly developed partially dried formulation of selected components of ETVAX.. A total number
      of 126 subjects will be included in each arm of the study, i.e. 252 subjects in total.
      Assuming a 10% dropout rate the target number of subjects to be recruited per study arm is
      therefore 140, i.e. 280 subjects in total. Healthy volunteers between 18-50 years will be
      eligible for enrolment into the study.

      Eligible subjects will be randomized on Day 1 (Visit 2) to receive either of the two oral
      formulations of ETVAX (1:1) and consecutively included the study. The treatment allocation
      (Wet formulation/Partially dried formulation) will be double-blind. The study subjects will
      receive two oral doses, two weeks apart (Day 1/Visit 2 and Day 15 /Visit 3).The dosing will
      occur at the clinic (CTC in Gothenburg, Sweden). A follow-up visit will be performed 7 days
      after the last (second) dose in all study subjects

      The primary endpoint to be measured for each patient in the study is response (yes/no) to a
      vaccine. A vaccine responder will be defined by a ≥2-fold increase in IgA and/or IgG antibody
      levels against LTB in serum between post- compared to pre-immunization samples. The response
      rates (seroconversion rates) of IgA and/or IgG anti-LTB antibodies in serum will be derived
      and compared between the two treatment groups.

      The secondary endpoint to be measured for each patient in the study is the occurrence of
      solicited symptoms for six days after each vaccination (day of vaccination and five
      subsequent days).

      Exploratory analyses will be done to evaluate if ETVAX vaccination induces circulating
      antigen specific memory B- and/or T cells that can be assessed using recently established
      laboratory assays.

      For the exploratory analyses, subgroups of subjects (n=20-40, evenly distributed between the
      two treatment arms) will participate in additional follow-up visits 5± 1, 30± 7 and 90± 14
      days after the second dose. Blood samples will be collected on all exploratory visits. The
      extra visits and analyses for exploratory analyses may continue after the main part of the
      study has been completed and the database locked.
    

Intervention name(s): Etvax; Etvax
Intervention type(s): Biological; Biological
Intervention description(s): Preparation of complete Wet formulation. The vaccine supplied as a liquid, is mixed with the 150 ml of sodium bicarbonate buffer solution on the day of preparation for use on dosing day.
Just prior to administration 10 µg of dmLT is added by pipette (50 µl).; Preparation of partially dry formulation. The partially dry formulation of vaccine is prepared by adding the effervescent powder containing the dmLT and LCTBA to 150 ml of water. After mixing, the content of the vaccine vial is added to the mixture and the vaccine is administered to the volunteer within 30 minutes after adding the buffer powder to the water.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A randomized, placebo controlled phase 2
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Prophylaxis against diarrhea due to enterotoxigenic E. coli