phase ii study to evaluate safety and immunogenicity of a chikungunya vaccine

Conditions: Chikungunya Virus Infection

Summary: the purpose of this study is to evaluate the immunogenicity and safety of a novel vaccine against chikungunya virus after one or two vaccinations by comparison of two different dose levels.

this is a double blinded, block-randomized, active- and placebo controlled, phase ii trial, comparing two dose levels by assessing immunogenicity, safety and tolerability of mv-chik (a novel vaccine against chikungunya virus). healthy male and female subjects aged 18-55 years will be randomized to one of six treatment groups (a, b, c. d, m1 or m2) differing in dosage and scheduling of vaccinations. group a-d will be split in one arm receiving mv-chik and one control-arm receiving priorix®. all subjects of group a. b, c and d will receive three i.m. injections on study day 0, 28 and 196. subjects of group a and b will receive mv-chik low dose or control-vaccine priorix® (or equivalent measles vaccine) and subjects of group c and d will be treated with mv-chik high dose or control-vaccine (priorix® or equivalent measles vaccine). all subjects of group a, b, c and d additionally will be randomized to one of two treatment sequences: group a and c will receive mv-chik or control-vaccine priorix® on study day 0 and 28, followed by placebo on day 196, and group b and d receive placebo on day 0 and mv-chik or priorix® on day 28, followed by an additional vaccination of the same product on day196 (boosting vaccination). all subjects of the measles booster group m1 and m2 will receive five i.m. injections on study day -28, 0, 28, 168 and 196. the first vaccination will be priorix® (or equivalent measles vaccine) on study day -28. group m1 will receive mv-chik vaccinations on day 0 and day 28 and placebo on day 168 and 196. group m2 will receive placebo on day 0 and 28 and mv-chik on day 168 and on day 196. all subjects will be followed for safety and immunogenicity evaluation until day 224. study duration per subject is estimated to be 33-37 weeks (\~8 months), respectively.

Eligibility criteria:
inclusion criteria: 1. signed informed consent obtained before any trial-related activities. 2. ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the investigator and to comply with the requirements of the entire study 3. available for the duration of the trial 4. healthy men or women aged \>18 and \<55 years 5. in female subjects either childbearing potential terminated by surgery or one year post-menopausal, or a negative urine pregnancy test during screening and the willingness not to become pregnant during the entire study period by practicing reliable methods of contraception as specified in protocol 6. normal findings in medical history and physical examination or the investigator considers all abnormalities to be clinically irrelevant 7. normal laboratory values or the investigator considers all abnormalities to be clinically irrelevant (unless otherwise specified in exclusion criteria) exclusion criteria: 1. participation in another clinical study within the past month in which the subject has been exposed to an investigational product (pharmaceutical product or placebo or device) or planned concurrent participation in another clinical study during the study period 2. history of immunodeficiency, known human immunodeficiency virus (hiv) infection, current hepatitis b/c infection, 3. drug addiction including alcohol dependence 4. inability or unwillingness to avoid more than the usual intake of alcohol during the 48 hours after vaccination (not more than 20g alcohol per day, which equals 0.5 l beer or 0.25 l of wine) 5. persons who are accommodated in an institution on court or official order. 6. persons in direct relationship with the sponsor, an investigator or other study site staff. direct relationship includes relatives or close dependents (children, spouse/partner, siblings or parents), as well as employees (site or sponsor). 7. non-study licensed vaccines: vaccination within 4 weeks prior to first vaccination or planning to receive any non-study vaccine during the study period. 8. measles vaccination or booster within the last 5 years or during the clinical study 9. prior receipt of any chikungunya vaccine 10. blood donations during 1 month prior to screening visit and throughout the study 11. recent infection (within 1 week prior to screening visit) (if non-serious, can be basis for temporary deferral) 12. relevant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory or neurological diseases, that in the opinion of the investigator may interfere with the aim of the study 13. history of neoplastic disease (excluding non-melanoma skin cancer that was successfully treated) within the past 5 years or a history of any hematological malignancy. 14. history of autoimmune disease (e.g. rheumatoid arthritis, systemic lupus erythematosus (sle), autoimmune thyroid disease). 15. history of moderate or severe arthritis or arthralgia within the past 3 months prior to screening visit. 16. behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol. 17. history of severe adverse reactions to vaccine administration, including anaphylaxis and related symptoms, such as urticaria, respiratory difficulty, angioedema and abdominal pain to vaccines, or history of allergic reaction likely to be exacerbated by any component of the vaccine. 18. history of anaphylaxis to drugs or major allergic reactions in general, which the investigator considers may compromise the safety of the volunteers 19. clinically relevant abnormal laboratory values indicative of physical illness * hematology: hemoglobin, hematocrit, erythrocyte count, differential white blood count, platelets * chemistry: creatinine (≥1.7 mg/dl), potassium, sodium, calcium, aspartate transaminase/alanine aminotransferase (ast/alt) ≥ 2.6 upper limit of normal (uln), alkaline phosphatase, bilirubin * coagulation parameter: prothrombin time (pt), activated partial thromboplastin time (aptt), fibrinogen according to the evaluation of the principle investigator * urinalysis according to the evaluation of the principle investigator 20. use of medication during 2 weeks before the first vaccination and throughout the study, which the investigator considers may affect the validity of the study except hormonal contraception in female subjects; prior to taking any medication during 72 h prior to the first vaccination, the study center should be consulted. 21. immunosuppressive drugs: use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination, or anticipated use during the trial. 22. receipt of blood products or immunoglobulins within 120 days prior to screening visit or anticipated receipt of any blood products or immunoglobulin during the trial. 23. pregnancy (positive pregnancy test at screening or during study phase), lactation or unreliable contraception in female subjects with child-bearing potential (for details please refer to section 8.3.6) 24. subjects with any condition which in the opinion of the investigator makes the subject unsuitable for inclusion 25. individuals who are living and/or working with severely immunocompromised people, children under 15 months old or pregnant women. 26. inability or unwillingness to provide informed consent and to abide by the requirements of the study 27. refusal to allow storage of specimens for future research. 28. regular blood plasma donations

Keywords: chikungunya, infectious disease