Dose-Confirmation, Immunogenicity and Safety Study of the Clostridium Difficile Vaccine Candidate VLA84 in Healthy Adults Aged 50 Years and Older. Phase II Study
Condition: Clostridium Difficile
MeSH terms: Clostridium Infections
Intervention: VLA84; Placebo
Intervention description: a recombinant fusion protein consisting of truncated Clostridium difficile (C. difficile) Toxin A and Toxin B; phosphate buffered saline (PBS) solution
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 500.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Clostridium difficile; Valneva; Phase 2; Healthy adults

Summary:

      Phase 2, randomized, observer-blind, placebo-controlled, multi-centric study including 4
      parallel study groups.

      500 Subjects (thereof, 250 aged 50 - 64 years and 250 aged 65 years and older) will be
      randomized in a (3:3:3:1) ratio to receive either VLA84 75 µg w/o (without) Alum, VLA84 200
      µg w/o Alum, VLA84 200 µg w/ (with) Alum (150 subjects each), or placebo (50 subjects), as
      i.m. (intramuscular) vaccinations into alternating arms, on Days 0, 7 and 28
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects aged ≥50 years of good general health, including subjects with
             pharmacologically controlled conditions like hypercholesterolemia, hypertension, or
             type 2 diabetes mellitus.

          -  Informed consent form has been signed and dated

        Exclusion Criteria:

          -  Subjects with any confirmed or suspected prior Clostridium difficile infection episode

          -  Previous vaccination against Clostridium difficile with any (investigational) vaccine
             or receipt of (investigational) monoclonal antibodies against Clostridium difficile
             toxins

          -  Use of any other investigational or non-registered medicinal product within 30 days
             prior to VLA84 vaccination at Visit 1 (Day 0) and throughout the entire study period.

          -  Active or passive vaccination four weeks before first vaccination at Visit 1 and
             during the entire study period, except for influenza (seasonal or pandemic) and
             pneumococcal vaccines which may be administered outside a 7-days interval before and
             after any trial vaccination

          -  Subject is pregnant, or lactating, or of childbearing potential (to be considered of
             non-childbearing potential, a female must be post-menopausal for at least 1 year or
             surgically sterile)

          -  Known thrombocytopenia, bleeding disorder, or receipt of anticoagulants in the 3 weeks
             preceding inclusion or until Visit 4 (Day28), contraindicating i.m. vaccination as
             judged by the investigator

          -  Clinically relevant renal, hepatic, cardiac, pulmonary or central nervous disorders,
             as judged by the investigator. Subjects with hypercholesterolemia, hypertension, or
             type 2 diabetes mellitus requiring medication are allowed if disease is adequately
             controlled

          -  Receipt of blood or blood-derived products in the past 3 months or anticipation of
             such products during the study period

          -  Known congenital, hereditary or acquired immunodeficiency, including known infection
             with human immunodeficiency virus (HIV), administration of chronic (defined as longer
             than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior
             to VLA84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 35).
             For corticosteroids this means prednisone or equivalent ≥ 0.05 mg/kg/day; topical and
             inhaled steroids are allowed. Periodic steroid injections, e.g., intra-articular, are
             not allowed within 30 days prior to first VLA84 vaccination at Visit 1 (Day 0) and
             until Visit 5 (Day 35)

          -  History of autoimmune disease, including Type I Diabetes mellitus. Subjects with
             vitiligo or thyroid disease taking thyroid hormone replacement are not excluded

          -  Any malignancy in the past 5 years. If treatment for cancer was successfully completed
             more than 5 years ago and the malignancy is considered to be cured, the subject may be
             enrolled

          -  Known hypersensitivity or allergic reactions to one of the components of the vaccine

          -  Inability or unwillingness to provide informed consent

          -  Persons who are committed to an institution (by virtue of an order issued either by
             the judicial or the administrative authorities)

          -  Persons who are in a dependent relationship with the sponsor, an investigator or other
             study team members, or the study center. Dependent relationships include close
             relatives and household members (i.e., children, partner/spouse, siblings, parents) as
             well as employees of the investigator or study center personnel