Safety, Tolerability and Long-term Immunogenicity of Different Formulations of a Chikungunya Vaccine (V184-005)

• ClinicalTrials.gov Identifier: NCT03635086
• Recruitment Status: Completed
• First Posted: August 17, 2018
• Results First Posted: October 20, 2021
• Last Update Posted: October 22, 2021
• Sponsor: Themis Bioscience GmbH
• Information provided by (Responsible Party): Themis Bioscience GmbH

Tracking Information

• First Submitted Date: July 24, 2018
• First Posted Date: August 17, 2018
• Results First Submitted Date: August 17, 2021
• Results First Posted Date: October 20, 2021
• Last Update Posted Date: October 22, 2021
• Actual Study Start Date: August 22, 2018
• Actual Primary Completion Date: January 25, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2021)

Geometric Mean Titer of Anti-Chikungunya Antibodies as Measured by 50% Plaque Reduction Neutralization Test 28 Days After Last MV-CHIK Vaccination [ Time Frame: 28 days after last vaccination (Up to Day 56) ]

Participant serum was collected for determination of antibody responses by 50% plaque reduction neutralization test (PRNT50). Geometric Mean Titer (GMT) of functional antibodies as measured by PRNT50 were assessed. Geometric mean titers and GMT ratios were estimated by applying an analysis of variance (ANOVA) including the factor treatment group. This was done using log10 transformed data and taking the anti-log of the resulting point estimates for the least squares means, least squares means differences and the corresponding 2 sided 95% confidence intervals (CI). P-values were also provided to compare GMTs between treatment groups adjusted for multiple comparisons according to Tukey Kramer.

Original Primary Outcome Measures (submitted: August 14, 2018)

Presence of functional antibodies as determined by the plaque reduction neutralisation test 28 days after last vaccination with MV-CHIK [ Time Frame: 28 days ]

Immunogenicity 28 days after the last MV-CHIK vaccination confirmed by the presence of functional antibodies as determined by the plaque reduction neutralisation test (PRNT50)

Current Secondary Outcome Measures (submitted: September 22, 2021)

• Percentage of Participants With Solicited and Unsolicited Adverse Events [ Time Frame: Up to Day 56 ]
  An adverse event (AE) includes any untoward medical occurrence in a participant to whom an IMP has been administered, not necessarily caused by or related to that product. An AE can therefore be any unfavourable or unintended sign, abnormal laboratory finding, symptom or disease temporally associated with the use of an IMP whether or not considered related to the IMP. The percentage of participants with solicited and unsolicited AEs was assessed.
• Percentage of Participants With at Least 1 Serious Adverse Event [ Time Frame: Up to Day 56 ]
  A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and consists of a congenital anomaly, birth defect or other important medical events. As per the protocol, adverse events were analyzed per treatment group but were not assessed with respect to individual vaccinations.
• Geometric Mean Titer of Anti-Chikungunya Antibodies as Measured by PRNT50 [ Time Frame: Up to Day 365 ]
  Participant serum was collected at each visit (Day 0, 28, 56, 182, and 365) for determination of antibody response by PRNT50. These results represent geometric mean titers (titers <10 were set to 5 for protocol-specified analysis).
• Percentage of CD4+CD69+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Percentage of CD4+CD69+CD137+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Percentage of CD4+CD137+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Percentage of CD4+CD69+OX40+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Percentage of CD4+OX40+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity will be determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of subjects.
• Percentage of CD8+CD69+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Percentage of CD8+CD69+CD137+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Percentage of CD8+CD137+ Chikungunya Virus Specific T-Cells [ Time Frame: Up to Day 56 ]
  Cellular immunogenicity was determined by the evaluation of T cell immune response. Blood was collected for the isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from whole blood to determine functional Interleukin 2 (IL-2)-producing T cells on day 0, 14, 28, 42, and 56 and in a subset of participants.
• Geometric Mean Titer of Anti-Chikungunya Antibodies Determined by Enzyme Linked Immunosorbent Assay [ Time Frame: Up to Day 365 ]
  Participant serum was collected at each visit (Day 0, 28, 56, 182, and 365) for determination of Chikungunya antibody response by enzyme linked immunosorbent assay (ELISA). The analysis of variance GMT of Chikungunya-ELISA antibodies between treatment groups is summarized.
• Geometric Mean Titer of Anti-Measles Antibodies Determined by ELISA [ Time Frame: Up to Day 56 ]
  Participant serum was collected at each visit (Day 0, 28, and 56) for determination of antibody responses by ELISA.
• Number of Participants With Abnormal Laboratory Hematology Values Reported as an AE [ Time Frame: Up to Day 56 ]
  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Abnormal laboratory hematology value was any AE reported under the System Organ Class of Investigations that was related to an abnormal laboratory hematology value.
• Number of Participants With Abnormal Laboratory Chemistry Values Reported as an AE [ Time Frame: Up to Day 56 ]
  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Abnormal laboratory chemistry value was any AE reported under the System Organ Class of Investigations that was related to an abnormal laboratory chemistry value.

Original Secondary Outcome Measures (submitted: August 14, 2018)

• Rate of solicited and unsolicited adverse events [ Time Frame: 56 days ]
  Rate of solicited and unsolicited adverse events during the treatment period until day 56
• Monitoring Serious adverse events [ Time Frame: 56 days ]
  Serious adverse events during the treatment period until study day 56
• Presence of functional antibodies as determined by the plaque reduction neutralisation test [ Time Frame: 365 days ]
  Presence of functional antibodies as determined by the plaque reduction neutralisation test will be determine with immunogenicity on days 0, 28 (group A, B, C, and D), days 0, 56 (group E) and long-term immunogenicity on day 182 (6 Mo) and 365 (12 Mo)
• Analyis of T cell responses induced by one or two immunisations [ Time Frame: 56 days ]
  Cellular response will be investigated by T cell analysis on PBMCs isolated at Visit 1(day 0), Visit 2 (day 14), Visit 3 (day 28), Visit 4 (day 42) and Visit 5 (day 56)
• Measurement of anti-Chikungunya antibodies determined by enzyme linked immunosorbent assay (ELISA) [ Time Frame: 365 days ]
  Measurement of anti-Chikungunya antibodies on days 0, 28, 56, 182 and 365 determined by enzyme linked immunosorbent assay (ELISA)
• Measurement of anti-Measles antibodies determined by enzyme linked immunosorbent assay (ELISA) [ Time Frame: 56 days ]
  Measurement of anti-Measles antibodies on days 0, 28, 56 determined by enzyme linked immunosorbent assay (ELISA)
• Measurement of induction of Chikungunya specific immune responses determined by T-cell assay [ Time Frame: 56 days ]
  Induction of Chikungunya specific immune responses on days 0, 14, 28, 42 and 56 determined by T-cell assay

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability and Long-term Immunogenicity of Different Formulations of a Chikungunya Vaccine (V184-005)
• Official Title: Observer Blinded, Randomised Study to Investigate Safety, Tolerability and Long-term Immunogenicity of Different Dose Regimens and Formulations of MV-CHIK in Healthy Volunteers
• Brief Summary: The purpose of this study is to investigate immunogenicity and safety of Measles Virus-Chikungunya (MV-CHIK) vaccine in different dose regimens, 28 days after one or two vaccinations.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Chikungunya Virus Infection

Intervention

• Biological: MV-CHIK lyophilised formulation, low dose
  MV-CHIK, a live-attenuated recombinant measles vaccine expressing Chikungunya virus antigens, lyophilized low dose (powder for suspension in water for intramuscular [IM] injection): 5x10^4 ±0.5 log tissue culture infectious dose 50 (TCID50)/dose.
• Biological: MV-CHIK liquid frozen formulation, low dose
  MV-CHIK, a live-attenuated recombinant measles vaccine expressing Chikungunya virus antigens, liquid frozen low dose (suspension for IM injection): 1x10^5 ±0.5 log TCID50/dose.
• Biological: MV-CHIK SPS® formulation, low dose
  MV-CHIK, a live-attenuated recombinant measles vaccine expressing Chikungunya virus antigens, liquid SPS® low dose (suspension for IM injection): 1x10^5 ±0.5 log TCID50/dose.
• Biological: MV-CHIK liquid frozen formulation, high dose
  MV-CHIK, a live-attenuated recombinant measles vaccine expressing Chikungunya virus antigens, liquid frozen high dose (suspension for IM injection): 1x10^6 ±0.5 log TCID50/dose.
• Other: Placebo
  Sterile physiological saline solution (0.9% sodium chloride [NaCl]), administered by IM injection.

Study Arms

• Experimental: Group A: Two MV-CHIK lyophilized low dose
  Participants received two vaccinations with MV-CHIK lyophilized formulation, low dose, on day 0 and day 28.
  Intervention: Biological: MV-CHIK lyophilised formulation, low dose
• Experimental: Group B: Two MV-CHIK liquid frozen low dose
  Participants received two vaccinations with MV-CHIK liquid frozen low dose formulation on day 0 and day 28.
  Intervention: Biological: MV-CHIK liquid frozen formulation, low dose
• Experimental: Group C: Two MV-CHIK liquid low dose stabilizing and protecting solution (SPS®)
  Participants received two vaccinations with MV-CHIK liquid low dose SPS® formulation on day 0 and day 28.
  Intervention: Biological: MV-CHIK SPS® formulation, low dose
• Experimental: Group D: Two MV-CHIK liquid frozen high dose
  Participants received two vaccinations with MV-CHIK liquid frozen high dose formulation on day 0 and day 28.
  Intervention: Biological: MV-CHIK liquid frozen formulation, high dose
• Experimental: Group E: One MV-CHIK liquid frozen high dose/placebo
  Participants received one vaccination with MV-CHIK liquid frozen high dose formulation on day 0 and placebo on day 28.
  Interventions:

  • Biological: MV-CHIK liquid frozen formulation, high dose
  • Other: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 14, 2018): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 16, 2019
• Actual Primary Completion Date: January 25, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Is able 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
• Has a negative serum pregnancy test at screening (for female participants)
• Has a willingness not to become pregnant or to father a child during the entire study period by practicing reliable methods of contraception
• Has availability during the duration of the trial

Exclusion Criteria:

• Has participated in another clinical study (including exposure to an investigational medicinal product or device) within one month before the screening visit or planned concurrent participation in another clinical study before completion of the treatment period
• Has a history of immunodeficiency, known human immunodeficiency virus (HIV) infection or current hepatitis B/C infection
• Has a history of drug addiction including alcohol dependence within the last 2 years
• Has an inability or unwillingness to avoid intake of more than around 20 grams alcohol per day during 48 hours after each vaccination (equals roughly 0.5 liter beer or 0.25 liter of wine)
• Has had a vaccination within 4 weeks prior to first vaccination or planning to receive any non-study vaccine until end of treatment period
• Has had a prior receipt of any Chikungunya vaccine
• Has a history of moderate or severe arthritis or arthralgia within the past 3 months prior to screening
• Has had a recent infection within 1 week prior to screening
• Has made blood donations including plasma donations, 90 days prior to screening visit and anticipated blood, plasma, tissue, sperm or organ donation, throughout the study until end of treatment period
• Has clinically relevant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory, autoimmune or neurological diseases or clinically relevant abnormal laboratory values, that in the opinion of the investigator may interfere with the aim of the study
• Has a 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
• Has behavioral, cognitive, or psychiatric condition that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol
• Has a 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
• Has a history of anaphylaxis to drugs or other allergic reactions, which the investigator considers compromising the safety of the participant.
• Use of medication during 2 weeks before the first vaccination and throughout the study, which the investigator considers affecting the validity of the study, except hormonal contraception or hormonal replacement therapy in female participants.
• Use of immunosuppressive drugs like corticosteroids (excluding topical preparations) within 30 days prior to the first vaccination or anticipated use before completion of the treatment period
• Has receipt of blood products or immunoglobulins within 120 days prior to the screening visit or anticipated receipt of any blood product or immunoglobulin before completion of the treatment period
• Has pregnancy (positive pregnancy test at screening or during the treatment period) or lactation at screening, or planning to become pregnant during the treatment period
• Has unreliable contraception methods
• Is a person in a direct relationship with the sponsor, an investigator or other study team members. Direct dependent relationships include close relatives (i.e. children, parents, partner/spouse, siblings) as well as employees of the study site or the sponsor

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03635086
• Other Study ID Numbers: V184-005; 2018-000211-25 ( EudraCT Number ); MV-CHIK-205 ( Other Identifier: Themisbio )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Themis Bioscience GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: Themis Bioscience GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Themis Bioscience GmbH
• Verification Date: October 2021