A Phase II Trial to Compare a Liquid-frozen and a Freeze-dried Formulation of IMVAMUNE (MVA-BN®) Smallpox Vaccine in Vaccinia-naïve Healthy Subjects
- Conditions
- Smallpox
- Interventions
- Biological: FD formulation of IMVAMUNE®Biological: LF formulation of IMVAMUNE®
- Registration Number
- NCT01668537
- Lead Sponsor
- Bavarian Nordic
- Brief Summary
A randomized, double-blind, multicenter Phase II trial to compare the immunogenicity and safety of a liquid-frozen and a freeze-dried formulation of IMVAMUNE (MVA-BN®) smallpox vaccine in vaccinia-naïve healthy subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 651
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2 FD formulation of IMVAMUNE® FD formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart Group 1 LF formulation of IMVAMUNE® LF formulation of IMVAMUNE® 2 doses of 1 x 10E8 TCID50, s.c., 4 weeks apart
- Primary Outcome Measures
Name Time Method ELISA GMT Week 6 Geometric Mean Titers (GMT) based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Titers below the detection limit are included with a value of '1'
- Secondary Outcome Measures
Name Time Method ELISA GMTs within 8 weeks Geometric Mean Titers (GMT) at all immunogenicity sampling time points based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). For the calculation of GMTs all measurements are included as they provide meaningful information even if below the detection limit (DL). Disregarding these measurements would highly bias the reported GMTs. We imputed values \<DL as a value of '1' and the GMT and corresponding 95% confidence intervals were calculated.
Number of Participants With Adverse Events of Special Interest (AESI) up to 32 weeks Occurrence, relationship to the trial vaccine and intensity of any Adverse Event of Special Interest (AESI). AESIs were defined as any cardiac symptoms and ECG changes determined to be clinically significant or cardiac enzyme troponin I elevated above 2 x the Upper Limit of Normal
PRNT GMT Week 6 Geometric Mean Titers (GMT) based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Titers below the detection limit are included with a value of '1'
Number of Participants With Serious Adverse Events up to 32 weeks Occurrence, relationship to the trial vaccine and intensity of any Serious Adverse Event (SAE).
PRNT GMTs within 8 weeks Geometric Mean Titers (GMT) at all immunogenicity sampling time points based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). For the calculation of GMTs all measurements are included as they provide meaningful information even if below the detection limit (DL). Disregarding these measurements would highly bias the reported GMTs. We imputed values \<DL as a value of '1' and the GMT and corresponding 95% confidence intervals were calculated.
ELISPOT Magnitudes of Response within 8 weeks Magnitudes of response of IFNγ producing T-cells measured by vaccinica-specific ELISPOT. Spot Forming Units below the detection limit are included as a value of '1'.
Percentage of Participants With Response by ELISPOT within 8 weeks Response rates regarding IFNγ producing T-cells measured by vaccinia-specific ELISPOT. A response to the vaccine was defined as either the appearance of a positive signal for participants without a positive signal at Baseline or an increase by a factor of at least 1.7 of the SFU/1 x 10E6 PBMC compared to the Baseline SFU/1 x 10E6 PBMC for participants with a positive signal at Baseline.
Percentage of Responders by ELISPOT within 8 weeks Responder rate measured by vaccinia specific ELISPOT. A participant was defined as a responder to the vaccine determined by ELISPOT if the participant had at least 1 post-baseline visit determined to be a response. A response to the vaccine was defined as either the appearance of a positive signal for participants without a positive signal at Baseline or an increase by a factor of at least 1.7 of the SFU/1 x 10E6 PBMC compared to the Baseline SFU/1 x 10E6 PBMC for participants with a positive signal at Baseline.
Correlation ELISA vs PRNT Titers within 8 weeks Pearson Correlation Coefficient between the ELISA titers and the PRNT titers at weeks 4, 6 and 8 based on the log10 transformed titer values
Number of Participants With Related Grade >=3 Adverse Events within 29 days after vaccination Occurrence of any Grade \>=3 Adverse Events related to the trial vaccine.
Number of Participants With Solicited Local Averse Events 8 days after any vaccination Occurrence and intensity of solicited local AEs (redness, swelling, induration, pruritus and pain) during the 8-day period (day of vaccination and the following 7 days) after any vaccination. Events were graded by intensity (1 = mild, 2 = moderate, 3 = severe).
Percentage of Participants With Seroconversion by PRNT within 8 weeks Seroconversion rates at all post-baseline immunogenicity sampling time points based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (2) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Number of Participants With Solicited General Adverse Events within 8 days after any vaccination Occurrence, intensity and relationship to the trial vaccines of solicited general AEs (pyrexia, headache, myalgia, nausea, fatigue and chills) during the 8-day period (day of vaccination and the following 7 days) after any vaccination. Events were graded by intensity (1 = mild, 2 = moderate, 3 = severe).
Percentage of Participants With Seroconversion by ELISA within 8 weeks Seroconversion rates at all post-baseline immunogenicity sampling time points based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Number of Participants With Unsolicited Adverse Events within 29 days after vaccination Occurrence, relationship to the trial vaccine and intensity of unsolicited treatment-emergent AEs (TEAEs).
Trial Locations
- Locations (3)
PRA
🇺🇸Lenexa, Kansas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States