Phase II Study to Evaluate Safety and Immunogenicity of a Chikungunya Vaccine

NCT ID: NCT02861586

Last Updated: 2021-10-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

263 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-17

Study Completion Date

2018-04-16

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chikungunya Virus Infection

Keywords

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Chikungunya, infectious disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Treatment Group A; MV-CHIK low

60 subjects will receive i.m. vaccinations with MV-CHIK low dose (5xE4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type EXPERIMENTAL

MV-CHIK low dose

Intervention Type BIOLOGICAL

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection, 5xE4 (± 0.5 log) TCID50/dose

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Treatment Group A/C; Priorix®

20 subjects will receive i.m. vaccinations with Priorix® on study day 0 and 28, placebo on day 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type ACTIVE_COMPARATOR

Priorix®

Intervention Type BIOLOGICAL

lyophilized mixed preparation containing the attenuated Schwarz measles virus strain, the RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain. Powder and solvent for suspension for injection

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Treatment Group B; MV-CHIK low

60 subjects will receive i.m. vaccinations with placebo on study day 0. MV-CHIK low dose (5xE4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type EXPERIMENTAL

MV-CHIK low dose

Intervention Type BIOLOGICAL

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection, 5xE4 (± 0.5 log) TCID50/dose

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Treatment Group B/D; Priorix®

20 subjects will receive i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type ACTIVE_COMPARATOR

Priorix®

Intervention Type BIOLOGICAL

lyophilized mixed preparation containing the attenuated Schwarz measles virus strain, the RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain. Powder and solvent for suspension for injection

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Treatment Group C; MV-CHIK high

60 subjects will receive i.m. vaccinations with MV-CHIK high dose (5xE5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type EXPERIMENTAL

MV-CHIK high dose

Intervention Type BIOLOGICAL

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection; 5xE5 (± 0.5 log) TCID50/dose

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Treatment Group D; MV-CHIK high

60 subjects will receive i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5xE5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type EXPERIMENTAL

MV-CHIK high dose

Intervention Type BIOLOGICAL

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection; 5xE5 (± 0.5 log) TCID50/dose

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Measles Booster Group 1

20 subjects will receive i.m. vaccinations with Priorix® on study day -28, MV-CHIK on day 0 and 28 and placebo on day 168 and 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type EXPERIMENTAL

MV-CHIK low dose

Intervention Type BIOLOGICAL

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection, 5xE4 (± 0.5 log) TCID50/dose

Priorix®

Intervention Type BIOLOGICAL

lyophilized mixed preparation containing the attenuated Schwarz measles virus strain, the RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain. Powder and solvent for suspension for injection

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Measles Booster Group 2

20 subjects will receive i.m. vaccinations with Priorix® on study day -28, placebo on day 0 and 28 and MV-CHIK on day 168 and 196.

Physical examinations, vital signs, pregnancy tests for females, inquiry of adverse events and collection of immunogenicity blood samples will be performed during all visits.

Group Type EXPERIMENTAL

MV-CHIK low dose

Intervention Type BIOLOGICAL

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection, 5xE4 (± 0.5 log) TCID50/dose

Priorix®

Intervention Type BIOLOGICAL

lyophilized mixed preparation containing the attenuated Schwarz measles virus strain, the RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain. Powder and solvent for suspension for injection

physiological saline solution

Intervention Type BIOLOGICAL

sterile physiological saline solution 0.9% used as placebo

Interventions

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MV-CHIK low dose

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection, 5xE4 (± 0.5 log) TCID50/dose

Intervention Type BIOLOGICAL

MV-CHIK high dose

recombinant measles virus vaccine expressing Chikungunya virus antigens, powder for suspension for injection; 5xE5 (± 0.5 log) TCID50/dose

Intervention Type BIOLOGICAL

Priorix®

lyophilized mixed preparation containing the attenuated Schwarz measles virus strain, the RIT 4385 strain of mumps virus (derived from the Jeryl Lynn strain) and the Wistar RA 27/3 rubella virus strain. Powder and solvent for suspension for injection

Intervention Type BIOLOGICAL

physiological saline solution

sterile physiological saline solution 0.9% used as placebo

Intervention Type BIOLOGICAL

Other Intervention Names

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vaccine against Chikungunya vaccine against Chikungunya vaccine against Measles, Mumps and Rubella 0.9% sodium chloride (NaCl)

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Themis Bioscience GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Hansa Sanatorium GmbH

Graz, , Austria

Site Status

Medical University Vienna, Department of Clinical Pharmacology

Vienna, , Austria

Site Status

Berliner Center for Travel- and Tropical Medicine

Berlin, , Germany

Site Status

Medicinal University Rostock, Department for Tropical Medicin and infectious diseases

Rostock, , Germany

Site Status

Countries

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Austria Germany

References

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Ramsauer K, Schwameis M, Firbas C, Mullner M, Putnak RJ, Thomas SJ, Despres P, Tauber E, Jilma B, Tangy F. Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial. Lancet Infect Dis. 2015 May;15(5):519-27. doi: 10.1016/S1473-3099(15)70043-5. Epub 2015 Mar 2.

Reference Type BACKGROUND
PMID: 25739878 (View on PubMed)

Tschismarov R, Zellweger RM, Koh MJ, Leong YS, Low JG, Ooi EE, Mandl CW, Ramsauer K, de Alwis R. Antibody effector analysis of prime versus prime-boost immunizations with a recombinant measles-vectored chikungunya virus vaccine. JCI Insight. 2021 Nov 8;6(21):e151095. doi: 10.1172/jci.insight.151095.

Reference Type DERIVED
PMID: 34582377 (View on PubMed)

Reisinger EC, Tschismarov R, Beubler E, Wiedermann U, Firbas C, Loebermann M, Pfeiffer A, Muellner M, Tauber E, Ramsauer K. Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial. Lancet. 2019 Dec 22;392(10165):2718-2727. doi: 10.1016/S0140-6736(18)32488-7. Epub 2018 Nov 5.

Reference Type DERIVED
PMID: 30409443 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-004037-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V184-002

Identifier Type: OTHER

Identifier Source: secondary_id

MV-CHIK-202

Identifier Type: -

Identifier Source: org_study_id