| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| The MV-CHIK vaccine candidate is developed to prevent infection with the mosquito borne Chikungunya Virus. This Phase 2 trial is designed to investigate the immunogenicity, safety and tolerability of MV-CHIK in healthy volunteers. Chikungunya virus causes Chikungunya fever, a febrile illness that can lead to debilitating arthritis that can last over months or years. The virus is endemic in the Indian Ocean Region, Afric, in most parts of Asia and since two years in the Americas. |
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| E.1.1.1 | Medical condition in easily understood language |
| The MV-CHIK vaccine candidate is developed to prevent infection with Chikungunya Virus. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To investigate the immunogenicity and safety of MV-CHIK 28 days after primary immunization regime, comprising one or two vaccinations. |
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| E.2.2 | Secondary objectives of the trial |
To investigate the immunogenicity, safety and tolerability of MV-CHIK booster dose 24 weeks after primary immunization
To investigate the immunogenicity, safety and tolerability of MV-CHIK during the vaccination period up to 28 days after the last vaccination of three or five vaccinations.
To identify dose and schedule of MV-CHIK to forward to Phase 3 clinical development
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Samples for shedding will only be collected from a subset of study subjects (of treatment groups A-D) that are enrolled at the study site in Vienna. Body fluids including saliva, urine and whole blood will be collected at Visits 1, 2, and 5. In addition, the subjects will be asked to return to the study site on days 7, 10 and 14 after the first immunization for collection of saliva, urine and whole blood. The participating subjects will sign a separate informed consent that describes the additional visits and procedures of sample collection. |
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| E.3 | Principal inclusion criteria |
1. Signed informed consent obtained before any trial-related activities. (Trial activities are any procedures that would not have been performed during normal management of the subject).
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 section 8.3.6.
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) |
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| E.4 | Principal 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 ½ L beer or ¼ 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, AST/ALT >= 2.6 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 |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Immunogenicity on day 56 confirmed by the presence of functional anti-chikungunya antibodies as determined by the plaque reduction neutralization test (PRNT50) |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
1. Immunogenicity at days 0, 28, 196 and 224; additionally for group M1 and M2 on day -28 and 168 as confirmed by the presence of functional anti-chikungunya antibodies as determined by the plaque reduction neutralization test (PRNT50) and by ELISA.
2. Measurement of anti-measles antibodies on days 0, 28, and 56; additionally for group M1 and M2 on day -28 as determined by ELISA.
3. Solicited local and systemic adverse events (AEs)
4. Serious adverse events (SAEs)
5. Rate of AEs during the 28 day post-vaccination period
6. Safety laboratory parameters (hematology, serum chemistry, urinalysis)
7. Shedding of live recombinant virus until day 196 (subset of subjects)
8. Induction of a Chikungunya virus specific T cell responses (subset of subjects)
9. Pre-existing anti-vector immunity:
- Immunogenicity of Chikungunya vaccine in the presence of recently boosted measles immunity (measles booster groups M1 and M2).
- Relation of post-vaccination anti-chikungunya plaque reduction neutralization titers (PRNT50) and baseline anti-measles ELISA titers (all treatment groups). |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Days 0, 28, 196 and 224; additionally for group M1 and M2 on day -28 and 168.
2. Days 0, 28, and 56; additionally for group M1 and M2 on day -28.
3. Starting from screening visit up to visit 6/28 days after vaccination
4. Starting from screening visit up to visit 6/28 days after vaccination
5. 28 day post-vaccination period
6. screening, day 56 and 224
7. Day 0, 7,10, 14, 28, 196
8. Day , 0, 28, 56, 196 and 224; additionally for group M1 and M2 on day -28 and 168
9. Day , 0, 28, 56, 196 and 224; additionally for group M1 and M2 on day -28 and 168
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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