An Open-label Study Assessing Safety, Immunogenicity and Dose Response of IC84

This is an open-label, partially randomized, dose escalation Phase 1 study which will consist of a part A in healthy adults aged between ≥18 and <65 years and a part B in healthy elderly ≥65 years, the latter age group being the most vulnerable population to suffer from C. difficile infections.

Part A consists of 3 vaccinations on Day0, Day7 and Day21 with the following groups:

Group A: IC84 20 mcg (microgram)with Alum Group B: IC84 75 mcg (microgram)with Alum Group C: IC84 75 mcg (microgram)without Alum Group D: IC84 200 mcg(microgram)with Alum Group E: IC84 200 mcg(microgram)without Alum

Part A was already finished and part B is now ongoing. All information which could be find under the other sections are referring to the information on Part B.

Inclusion criteria

• Healthy adults ≥18 years of age.
• No clinically relevant pathological findings in any of the investigations at the Screening Visit including subjects with pharmacologically controlled conditions like hypercholesterolemia, hypertension, cardiovascular disease or non insulin-dependent diabetes mellitus. Minor deviations of laboratory values from the normal range may be accepted, if judged by the investigator to have no clinical relevance.
• In female subjects, either childbearing potential terminated by surgery or 1 year post menopausal, or a negative serum pregnancy test during screening and the willingness not to become pregnant during the entire study period by practicing reliable methods of contraception.
• Weight: ≥ 45.5 kg and <= 150 kg at Visit 0 (Screening Visit).
• White blood cells ≥2,500/mm3 and <11,000/mm3 at Visit 0.
• Platelets within normal limits at Visit 0.
• Written informed consent obtained from the subject prior to any study related procedures.

Exclusion criteria

• Use of any other investigational or non-registered medicinal product within 30 days prior to IC84 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.
• Immunodeficiency including status post-organ-transplantation or immuno-suppressive therapy, and a family history of congenital or hereditary immunodeficiency.
• Infection with the human immunodeficiency virus (HIV, a negative test result within 30 days before screening is acceptable), Hepatitis B virus (HBV, Hepatitis B surface antigen [HBsAg]) or Hepatitis C virus (HCV).
• History of severe hypersensitivity reactions and anaphylaxis.
• History of allergic bronchial asthma and severe allergic rhinoconjunctivitis.
• Known hypersensitivity or allergic reactions to one of the components of the vaccine.
• 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.
• Clinically significant hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders, which are not adequately controlled by medical treatment within the last 12 weeks before IC84 vaccination at Visit 1 (Day 0) as judged by the site's Principal Investigator.
• Systemic antibiotic use within four weeks prior to first vaccination and during treatment period (until Day 28).
• Clinically significant diseases as judged by the investigator.
• Administration of chronic (defined as longer than 14 days) immunosuppressants or other immune-modifying drugs within 30 days prior to IC84 vaccination at Visit 1 (Day 0) and during the study until Visit 5 (Day 28). (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 IC84 vaccination at Visit 1 (Day 0) and until Visit 5 (Day 28).
• Intake of NSAID within three days prior to and within three days after all three vaccinations (Day 0, 7 and 21).
• Acute febrile infections or exacerbation of chronic infection within four weeks prior to first vaccination at Visit 1 and during treatment period (until Day 21).
• Body temperature > 37°C (oral) immediately prior to each vaccination.
• Drug addiction within 6 months prior to Visit 0 [including alcohol dependence, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day] indicated by an elevated MCV above normal value at the Screening Visit.
• Inability or unwillingness to avoid more than the usual intake of alcohol [i.e., not more then 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day] during the 48 hours after vaccination.
• Pregnancy (positive pregnancy test during screening), lactation or unreliable contraception in female subjects with child-bearing potential ( and unreliable contraception in male subjects.
• Not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
• Blood donation within 4 weeks prior to first vaccination.
• Clinically significant mental disorder not adequately controlled by medical treatment.
• History of Guillain-Barré-Syndrome (GBS).
• Any condition which might interfere with study objectives or would limit the subject's ability to complete the study in the opinion of the investigator.
• 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).