A Randomized, Double-blind, Multicenter Phase III Trial to Evaluate Immunogenicity and Safety of Three Consecutive Production Lots of a Freeze-dried Formulation of MVA-BN® Smallpox Vaccine in Healthy, Vaccinia-naïve Subjects

Bavarian Nordic10 sites in 1 country1,129 target enrollmentJune 19, 2019

ConditionsSmallpox

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Smallpox
Sponsor: Bavarian Nordic
Enrollment: 1129
Locations: 10
Primary Endpoint: Vaccinia-Specific Neutralizing Antibodies Measured by Plaque Reduction Neutralization Test (PRNT)
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 3 multicenter trial to evaluate safety and immune response of three consecutive production lots of freeze-dried (FD) MVA-BN smallpox vaccine. The vaccine will be given to healthy subjects who do not have a smallpox scar.

Approximately 1110 subjects will be randomly enrolled into one of three groups:

Group 1 will include 370 subjects, who will receive two separate injections (shot) with a short needle, given below the skin of the upper arm with 0.5 mL FD MVA-BN (Lot 1).

Group 2 will include 370 subjects, who will receive two separate injections (shot) with a short needle, given below the skin of the upper arm with 0.5 mL FD MVA-BN (Lot 2).

Group 3 will include 370 subjects, who will receive two separate injections (shot) with a short needle, given below the skin of the upper arm with 0.5 mL FD MVA-BN (Lot 3).

The primary objective of the trial is to show that the immune response elicited (produced) by three consecutively produced MVA-BN lots are statistically (numerically) comparable.

Registry

clinicaltrials.gov

Start Date

June 19, 2019

End Date

June 22, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bavarian Nordic

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The subject has read, signed and dated the ICF
•Body Mass Index ≥ 18.5 and \< 35
•Women of childbearing potential (WOCBP) must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the trial, and must avoid becoming pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal (defined as ≥ 12 months without a menstrual period) or surgically sterilized. Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products).
•WOCBP must have a negative serum pregnancy test at screening (please note: a negative urine pregnancy test is required within 24 hours prior to each vaccination)
•White blood cells ≥ 2500/mm3 \< ULN (Upper Limit of Normal)
•Absolute neutrophil count (ANC) within normal limits
•Hemoglobin within normal limits
•Platelets within normal limits
•Adequate renal function defined as a calculated Creatinine Clearance (CrCl) \> 60 mL/min as estimated by the Cockcroft-Gault equation: (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min). For women the result, calculated with the above formula, has to be multiplied by 0.85 = CrCl (mL/min)
•Adequate hepatic function defined as: Total bilirubin ≤ 1.5 x ULN in the absence of other evidence of significant liver disease Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 1.5 x ULN

Exclusion Criteria

•Typical vaccinia scar
•Known or suspected history of smallpox vaccination
•History of vaccination with any poxvirus-based vaccine
•US Military service prior to 1991 or after January 2003
•Pregnant or breast-feeding women
•Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
•History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject or would limit the subject's ability to complete the trial
•History of or active autoimmune disease, persons with vitiligo or thyroid disease taking thyroid replacement are not excluded
•Known or suspected impairment of immunologic function including, but not limited to, human immunodeficiency virus (HIV) Infection, clinically significant liver disease (including chronic active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection), diabetes mellitus
•History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous tumor site.

Outcomes

Primary Outcomes

Vaccinia-Specific Neutralizing Antibodies Measured by Plaque Reduction Neutralization Test (PRNT)

Time Frame: Two weeks post second vaccination; approximately Week 6.

Vaccinia-specific neutralizing antibody titers below the lower limit of quantitation are given a value 10, i.e., half of the PRNT lower limit of quantitation of 20.

Secondary Outcomes

Vaccinia-Specific Total Antibodies Measured by Enzyme-Linked Immunosorbant Assay (ELISA)(Two weeks post second vaccination; approximately Week 6.)
Occurrence of Any Grade 3 or 4 Unsolicited AEs Probably, Possibly or Definitely Related to the Trial Vaccine(Within 28 days (and up to 35 days) after each vaccination, ie, from Visit 1 to Visit 3 for the first vaccination and from Visit 3 to Visit 5 for the second vaccination based on the protocol scheduled visits.)
Seroconversion Rates for Vaccinia-Specific Neutralizing Antibodies by PRNT(Two weeks post second vaccination; approximately Week 6.)
Seroconversion Rates for Vaccinia-Specific Total Antibodies by ELISA(Two weeks post second vaccination; approximately Week 6.)
Occurrence, Relationship and Intensity of Unsolicited AEs(Within 28 days (and up to 35 days) after each vaccination, ie, from Visit 1 to Visit 3 for the first vaccination and from Visit 3 to Visit 5 for the second vaccination based on the protocol scheduled visits.)
Pearson Correlation Coefficient Between the log10 Transformed PRNT Titers and the log10 Transformed ELISA Titers(Two weeks post second vaccination; approximately Week 6.)
Occurrence, Relationship, and Intensity 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 each vaccination, ie Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits.)
Occurrence, Relationship and Intensity of Any Serious Adverse Event (SAE) at Any Time During the Trial(Overall study, ie from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.)
Duration of Solicited General AEs (Pyrexia [Body Temperature Increase], Headache, Myalgia, Nausea, Fatigue and Chills)(Starting during the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie, Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits, through resolution.)
Occurrence, Relationship and Intensity of Any Cardiac Sign or Symptom Indicating a Case of Myo-/Pericarditis at Any Time During the Trial.(Overall study, ie from first vaccination at Visit 1 through the Follow-up Visit approximately 32 weeks post first vaccination.)
Duration of Solicited Local AEs (Redness, Swelling, Induration, Pruritus and Pain).(Starting during the 8 day period (day of vaccination and the following 7 days) after each vaccination, ie, Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits, through resolution.)
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 each vaccination, ie Days 1-8 for the first vaccination and Days 28-35 for the second vaccination based on the protocol scheduled visits.)