Clinical Trial: Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE®
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase II, Randomized, Open-Label Study to Evaluate the Safety and Immunogenicity of IMVAMUNE® Using Three Immunization Schedules and Two Modes of Delivery
Brief Summary: Imvamune (licensed name of MVA being developed as a smallpox vaccine) has been tested in over 2,000 individuals and is on path for licensure. This study will be a Phase II to evaluate three different immunization schedules and two different modes of delivery. The study will look at condensed schedules. Study will randomize subjects to one of four arms.
Detailed Summary: This is a Phase II, randomized, open-label immunogenicity and safety study of different immunization schedules and delivery systems (syringe and needle vs. the Stratis™) in healthy, vaccinia-naïve adults 18 years to 40 years of age, inclusive. Approximately 352 subjects will be enrolled and randomized to one of four study arms. Study Arm A (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using a syringe and needle on Day 1 and 29. Study Arm B (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL per dose) via the SC route using a syringe and needle on Day 1 and 15. Study Arm C (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL) via the SC route using a syringe and needle on Day 1 and 22. Study Arm D (N=88) will receive a two dose regimen of IMVAMUNE® (1x10^8 TCID50/0.5 mL) via the SC route using the Stratis™ on Day 1 and 29. Immunogenicity assessments will be performed using ELISA and PRNT. Safety assessments will be done via solicited injection site and systemic reactions. Unsolicited AEs will be collected until 28 days post last injection and SAEs for the duration of the subjects' study participation. Safety laboratory assessments will be performed at baseline and 14 days after each vaccination. Primary outcome measures: For each subject, the peak PRNT will be defined as the highest titer among all available measurements post second vaccination; Occurrence of solicited local injection site reactions in subjects receiving vaccine via the Stratis™ compared to syringe and needle administration as collected on the memory aid and by in clinic assessment. Parent protocol to sub-study 13-0027.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Current Primary Outcome:
- Geometric Mean Peak Plaque Reduction Neutralization Titer (PRNT) After Second Vaccination [ Time Frame: Day 7 through Day 31 after 2nd vaccination ]Blood was collected from all participants at 8, 15, 22 and 29 days after receipt of the second vaccination for assessment of plaque reduction neutralization titers. The peak titer for each participant was defined as the highest titer among all available measurements post second vaccination. The geometric mean for each group was then assessed from individual participants' peak titers.
- Percentage of Participants Reporting Moderate or Severe Solicited Local Injection Site Reactions After Receiving Vaccine Via the Stratis™ Compared to Syringe and Needle Administration [ Time Frame: 15 days after each vaccination ]Participants maintained a memory aid to record daily the occurrence of local injection site reactions for 15 days after vaccination based on their interference with daily activities (pain and itchiness at injection site, underarm pain and swelling) or based on a quantitative measurement of the reaction (redness, swelling). In the subjective grading scale, severe reactions prevented daily activities, moderate reactions interfered with but did not prevent daily activities, and mild reactions were present but did not interfere with daily activities. For the quantitative scale, severe reactions greater than 30 millimeters (mm), moderate reactions were 15-30mm, and mild reactions were 1-15mm. Participants are counted by the maximum severity on any of the 15 days, and for this outcome measure, only those reporting moderate or severe events are counted. Formal comparisons by Fisher's Exact test were conducted for Arm D (Stratis, Day 1,29) compared to A
- For each subject, the peak Plaque reduction neutralization titer (PRNT) will be defined as the largest titer among all available measurements post second vaccination [ Time Frame: Day 1 after the first vaccination through Day 29 after the 2nd vaccination. ]
- Occurrence of solicited local injection site reactions in subjects receiving vaccine via the Stratis™ compared to syringe and needle administration as collected on the memory aid and by in clinic assessment [ Time Frame: Day 1 after the 1st vaccination to Day 29 after the 2nd vaccination. ]
- Geometric Mean Peak ELISA Titer After Second Vaccination [ Time Frame: Day 7 through 31 after the 2nd vaccination ]Blood was collected from all participants at 8, 15, 22 and 29 days after receipt of the second vaccination for assessment of antibody titers by ELISA. The peak titer for each participant was defined as the highest titer among all available measurements post second vaccination. The geometric mean for each group was then assessed from individual participants' peak titers.
- Number of Subjects Experiencing Serious Adverse Events (SAEs) Associated With IMVAMUNE [ Time Frame: Day 1 after the first vaccination through 180 days after the 2nd vaccination. ]Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation thereof; was a congenital anomaly/birth defect; or may have jeopardized the participant, or required intervention to prevent one of the outcomes. Association with IMVAMUNE was determined by the investigator and defined as "Related", meaning a reasonable possibility that the study product caused the adverse event. Reasonable possibility was defined as there being evidence to suggest a causal relationship between the study product and the adverse event.
- The occurrence of Serious Adverse Events (SAEs) associated with IMVAMUNE throughout the study (through last visit for each subject) for all four study arms [ Time Frame: Day 1 after the first vaccination through 180 days after the 2nd vaccination. ]
- For each subject, the peak ELISA titer will be defined as the highest titer among all available measurements post second vaccination [ Time Frame: Day 1 after the first vaccination through Day 29 after the 2nd vaccination. ]
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Institute of Allergy and Infectious Diseases (NIAID)
Dates:
Date Received: April 4, 2013
Date Started: June 2013
Date Completion:
Last Updated: July 28, 2016
Last Verified: May 2015
