Dose-finding Study to Evaluate Immunogenicity of Three Different Dose Levels of the IMVAMUNE (MVA-BN) Smallpox Vaccine.

Phase II, Double-blind, Randomised, Dose-finding Study to Evaluate the Immunogenicity of Three Different Doses of MVA-BN Smallpox Vaccine in 18-30 Year Old Smallpox naïve Healthy Subjects

The objective of the study is to find the optimal dose for the smallpox candidate vaccine IMVAMUNE (MVA-BN). For this purpose the study compares IMVAMUNE (MVA-BN) administered at three different dose levels.

Study Overview

• Status: Completed
• Conditions: Smallpox
• Intervention / Treatment: Biological: IMVAMUNE (MVA-BN)

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4123
    • Swiss Pharma Contract

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female subjects, aged 18 - 30 years
• Signed informed consent after being advised of the risks and benefits of the study in a language able to understand, and prior to performance of any study specific procedure.
• Free of obvious health problems with acceptable medical history by screening evaluation and physical examination.
• Subject of not of child-bearing potential or all of the following: A urine/serum ß-HCG pregnancy test gives a negative result, use of adequate contraceptive precautions for 30 days before first vaccination.

Exclusion Criteria:

• Known or suspected history of smallpox vaccination or typical vaccinia scar.
• Positive test result in MVA specific ELISA or PRNT at screening.
• Positive result in HIV or HCV antibody test at screening.
• HbsAG positive at screening.
• Pregnancy or breast-feeding.
• 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.
• History of autoimmune disease
• History of malignancy.
• History of chronic alcohol abuse and/or intravenous drug abuse.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• History of anaphylaxis or severe allergic reaction.
• Acute disease (a moderate or severe illness with or without a fever) at the time of enrolment.
• Any vaccinations within a period starting 30 days prior to administration of the vaccine and ending at study conclusion.
• Chronic administration of immuno-suppressants or other immune-modifying drugs.
• Administration or planned administration of immunoglobulins and/or any blood products during the study period.
• Use of any investigational or non-registered drug or vaccine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; healthy, vaccinia naïve subjects 2 x 10E7 TCID50 IMVAMUNE (MVA-BN), subcutaneous	Biological: IMVAMUNE (MVA-BN); Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.
Active Comparator: Group 2; healthy, vaccinia naïve subjects 5 x 10E7 TCID50 IMVAMUNE (MVA-BN), subcutaneous	Biological: IMVAMUNE (MVA-BN); Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.
Active Comparator: Group 3; healthy, vaccinia naïve subjects 1 x 10E8 TCID50 IMVAMUNE (MVA-BN), subcutaneous	Biological: IMVAMUNE (MVA-BN); Two vaccinations of 0.5 ml MVA-BN vaccine, separated by a 4 week interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ELISA seroconversion rate	Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit 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.	Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ELISA seroconversion rate	Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit 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.	Days 28, 84
ELISA GMT	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'.	Days 28, 42, 84
PRNT seroconversion rate	Seroconversion rate based on vaccinia-specific Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit 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.	Days 28, 42, 84
PRNT GMT	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'.	Days 28, 42, 84
Cytotoxic T-Lymphocyte response	The Cytotoxic T-Lymphocyte (CTL) response was determined by measuring IFNγ producing cells by Intracellular cytokine staining (ICS)	Days 28, 42, 84
Serious Adverse Events	Incidence, relationship and intensity of any Serious Adverse Event (SAE)	within 12 weeks
Solicited Local Adverse Events	Incidence and intensity of solicited local AEs. Percentages based on subjects with at least one completed diary card.	within 8 days after any vaccination
Solicited General Adverse Events	Incidence of solicited general AEs: Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.	within 8 days after any vaccination
Unsolicited Non-serious Adverse Events	Occurrence of unsolicited non-serious AEs: Intensity and relationship to vaccination	within 31 days after any vaccination

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Rolf Pokorny, M.D., Swiss Pharma

Publications and helpful links

General Publications

• von Krempelhuber A, Vollmar J, Pokorny R, Rapp P, Wulff N, Petzold B, Handley A, Mateo L, Siersbol H, Kollaritsch H, Chaplin P. A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE. Vaccine. 2010 Feb 3;28(5):1209-16. doi: 10.1016/j.vaccine.2009.11.030. Epub 2009 Nov 25.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: September 11, 2005
• First Submitted That Met QC Criteria: September 11, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Poxviridae Infections; Smallpox
• Other Study ID Numbers: POX-MVA-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No