A Phase II Study on Immunogenicity and Safety of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in Subjects With Atopic Dermatitis

A Multicenter, Open-label, Controlled Phase II Study to Evaluate Immunogenicity and Safety of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in 18-40 Year Old Subjects With Diagnosed Atopic Dermatitis

The purpose of this study is to compare the immunogenicity and safety of an investigational smallpox vaccine in subjects with atopic dermatitis to healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Biological: IMVAMUNE

• Study Type: Interventional
• Enrollment (Actual): 632
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 6760
    • Hospital General de Mexico
  • Mexico City, Mexico
    • CIFBIOTEC (Centro de Investigacion Farmacologica y Biotecnologica)
  • Mexico City, Mexico
    • Hospital Regional Lic. Adolfo Lopez Mateos. ISSSTE Ciudad de Mexico
  • Monterrey, Mexico, 64460
    • Centro Regional de Alergia e Inmunología Clínica del Hospital Universitario "Dr. José Eleuterio González"
  • Zapopan, Jalisco, Mexico, 45200
    • Hospital Angel Leañol, Dermatology
  • CP
    • Magdalena De Las Salinas, CP, Mexico, 07760
      • Hospital Juárez de México
  • Jalisco
    • Guadalajara, Jalisco, Mexico
      • Instituto Dermatólogico de Jalisco "Dr. Jose Barba Rubio"
• United States
  • Arizona
    • Tucson, Arizona, United States, 85745
      • Alta Clinical Research LLC
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
  • California
    • Garden Grove, California, United States, 92843
      • RX Clinical Research, Inc.
    • Vallejo, California, United States, 94589
      • Solano Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Adult & Pediatric Dermatology PC
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • University of Kentucky Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106-5239
      • Academic Dermatology Associates
  • New York
    • Rochester, New York, United States, 14623
      • Dermatology Associates of Rochester
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology & Research Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment & Research Center
    • San Antonio, Texas, United States, 78229
      • Dermatology Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Group 1 (Healthy Participants):

Subjects without present or history of any kind of atopy.

Group 2 (Atopic Dermatitis Participants):

Subjects with diagnosed atopic dermatitis.

All study subjects:

1. Male and female subjects between 18 and 40 years of age without history of smallpox vaccination.
2. Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination.
3. Women of childbearing potential 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 study, and must not become pregnant for at least 28 days after the last vaccination.
4. Lab values without clinically significant findings.
5. Electrocardiogram (ECG) without clinically significant findings.

Exclusion Criteria:

1. Pregnant or breast-feeding women.
2. Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
3. History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
4. Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
5. 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 at the vaccination site are excluded.
6. History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure.
7. History of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years.
8. Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool: (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE: This criterion applies only to volunteers 20 years of age and older.
9. History of anaphylaxis or severe allergic reaction.
10. Post organ transplant subjects whether or not receiving chronic immunosuppressive therapy.
11. Administration of immunomodulatory substances.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Participants; Healthy, vaccinia naive subjects without Atopic Dermatitis, receiving two doses of MVA-BN (IMVAMUNE)	Biological: IMVAMUNE; Subjects receiving two subcutaneous vaccinations; Other Names: MVA-BN
Experimental: Atopic Dermatitis Participants; Vaccinia naive subjects with diagnosed Atopic Dermatitis. "Diagnosed" AD included subjects with either history of or subjects with currently active AD (defined as scoring AD [SCORAD] <= 30), receiving two doses of MVA-BN (IMVAMUNE)	Biological: IMVAMUNE; Subjects receiving two subcutaneous vaccinations; Other Names: MVA-BN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroconversion by ELISA	Seroconversion rate based on 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.	week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroconversion by ELISA	Seroconversion rate based on 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.	within 32 weeks
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'.	within 32 weeks
Percentage of Participants With Seroconversion by PRNT	Seroconversion rate based on Plaque Reduction Neutralization Test (PRNT). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (15) 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.	within 32 weeks
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'.	within 32 weeks
ELISPOT IFN-γ Values	Number of interferon gamma (IFN-γ) secreting peripheral blood mononuclear cells (PBMC) per 10^6 PBMC in response to restimulation with MVA-BN detected by ELISPOT assay	within 6 weeks
Number of Participants With SAEs	Occurrence, relationship and intensity of any serious AE (SAE)	within 32 weeks
Number of Participants With Related Grade >=3 Adverse Events	Number of Participants with any Grade >=3 Adverse Event probably, possibly, or definitely related to the study vaccine. Pooled solicited (general) and unsolicited AEs.	within 29 days after vaccination
Number of Participants With Solicited Local Adverse Events	Number of Participants with and Intensity of solicited local AEs (erythema, swelling and pain). Percentages based on subjects with at least one completed diary card.	within 8 days after any vaccination
Number of Participants With Solicited General AEs	Number of Participants with solicited systemic/general AEs (elevated body temperature, headache, myalgia, nausea, fatigue and chills): Intensity and relationship to vaccination. Percentages based on subjects with at least one completed diary card.	within 8 days after any vaccination
Number of Unsolicited Non-serious Adverse Events: Intensity	Occurrence of unsolicited non-serious AEs by Intensity	within 29 days after any vaccination
Number of Unsolicited Non-serious Adverse Events: Relationship to Vaccination	Occurrence of unsolicited non-serious AEs by relationship to study vaccine	within 29 days after any vaccination

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Richard N Greenberg, M.D., University Of Kentucky School of Medicine

Publications and helpful links

General Publications

• Greenberg RN, Hurley MY, Dinh DV, Mraz S, Vera JG, von Bredow D, von Krempelhuber A, Roesch S, Virgin G, Arndtz-Wiedemann N, Meyer TP, Schmidt D, Nichols R, Young P, Chaplin P. A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis. PLoS One. 2015 Oct 6;10(10):e0138348. doi: 10.1371/journal.pone.0138348. eCollection 2015. Erratum In: PLoS One. 2015;10(11):e0142802. Hurley, Yadira [corrected to Hurley, Maria Yadira].

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: April 20, 2006
• First Submitted That Met QC Criteria: April 20, 2006
• First Posted (Estimate): April 21, 2006

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Vaccination; Atopic dermatitis; Smallpox
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; DNA Virus Infections; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Poxviridae Infections; Dermatitis; Eczema; Dermatitis, Atopic; Smallpox
• Other Study ID Numbers: POX-MVA-008; HHSN266200400072C (NIAID)