A Randomized, Double-blind, Placebo-controlled Study on Immunogenicity and Safety of MVA-BN (IMVAMUNE™) Smallpox Vaccine in Healthy Subjects

NCT00316524 | Completed Phase 2 Results

• 3 other identifiers: POX-MVA-005DMID 05-0128EudraCT No. 2005-001781-14
• Study Type: interventional
• Target: 745
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the immune response after a single vaccination of pre-immune subjects compared to two vaccinations in naive subjects. In addition the study further investigates the cardiac safety profile of MVA-BN® in a healthy population compared to placebo.

Conditions

Smallpox

Keywords

Smallpox; Vaccination; Prevention

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Seroconversion by ELISA

  Seroconversion rate 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.

  2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)

• Number of Participants With ECG Changes

  Occurrence of any specific or unspecific ECG change. Assessments at Screening (SCR), Visit 2 (Week 2) and Visit 4 (Week 6).

  within 2 weeks after each vaccination

• Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])

  Occurrence and relationship of any other cardiac symptom at any time during the study

  within 32 weeks

Secondary Outcomes (8)

• Percentage of Participants With Seroconversion by ELISA

  4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)

• Percentage of Participants With Seroconversion by PRNT

  2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)

• Percentage of Participants With Seroconversion by PRNT

  4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4)

• Number of Participants With Related Serious Adverse Events

  within 32 weeks

• Number of Participants With Solicited Local Adverse Events

  within 8 days after any vaccination

Study Arms (4)

GP 1: two x 1x10E08 TCID, MVA-BN® s.c., vaccinia naive

EXPERIMENTAL

vaccinia naive subjects receiving two subcutanenous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)

Biological: MVA-BN® (IMVAMUNE)

GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive

EXPERIMENTAL

vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)

Biological: MVA-BN® (IMVAMUNE); Biological: Placebo

GP 3: two x Placebo, s.c., vaccinia naive

PLACEBO COMPARATOR

vaccinia naive subjects, receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer).

Biological: Placebo

GP 4: 1x10E08 TCID, MVA-BN®, s.c., vaccinia experienced

EXPERIMENTAL

vaccinia experienced subjects, receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID).

Biological: MVA-BN® (IMVAMUNE)

Interventions

MVA-BN® (IMVAMUNE) BIOLOGICAL

1x 10E8\_TCID50

GP 1: two x 1x10E08 TCID, MVA-BN® s.c., vaccinia naive; GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive; GP 4: 1x10E08 TCID, MVA-BN®, s.c., vaccinia experienced

Placebo BIOLOGICAL

Tris-Buffer

GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive; GP 3: two x Placebo, s.c., vaccinia naive

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects between 18 and 55 years of age.
• Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination.
• 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. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products.)
• Lab values without clinically significant findings
• Electrocardiogram (ECG) without abnormal findings (e.g. any kind of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV-node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).
• Groups 1, 2 and 3 (All vaccinia-naïve subjects) additionally:
• No history of known or suspected previous smallpox vaccination.
• No detectable vaccinia scar.
• Group 4 (All previously vaccinated subjects) additionally:
• History of previous smallpox vaccination (documented and/or typical vaccinia scar).
• Most recent smallpox vaccination ≥ 5 years.

You may not qualify if:

• Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
• 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, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
• 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.
• History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
• History of an immediate family member (father, mother, brother, or sister) who died due to ischemic heart disease before age 50 years.
• 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.
• History of anaphylaxis or severe allergic reaction.
• Immune modulatory therapy.
• History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject.
• History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.

Sponsors & Collaborators

• Bavarian Nordic: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Harrison Clinical Research GmbH

Munich, Bavaria, 80636, Germany

Location

Related Publications (2)

• Zitzmann-Roth EM, von Sonnenburg F, de la Motte S, Arndtz-Wiedemann N, von Krempelhuber A, Uebler N, Vollmar J, Virgin G, Chaplin P. Cardiac safety of Modified Vaccinia Ankara for vaccination against smallpox in a young, healthy study population. PLoS One. 2015 Apr 16;10(4):e0122653. doi: 10.1371/journal.pone.0122653. eCollection 2015.

  PMID: 25879867 RESULT

• Ilchmann H, Samy N, Reichhardt D, Schmidt D, Powell JD, Meyer TPH, Silbernagl G, Nichols R, Weidenthaler H, De Moerlooze L, Chen L, Chaplin P. One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines. J Infect Dis. 2023 May 12;227(10):1203-1213. doi: 10.1093/infdis/jiac455.

  PMID: 36408618 DERIVED

MeSH Terms

Conditions

Smallpox

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Program Lead, Clinical Operations
• Organization: Bavarian Nordic A/S

info@bavarian-nordic.com

+45 3326

Study Officials

• Frank von Sonnenburg, Prof

  Section of International Medicine & Public Health, Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians Unviersity Munich

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2006
• First Posted: April 21, 2006
• Study Start: April 1, 2006
• Primary Completion: February 1, 2007
• Study Completion: August 1, 2007
• Last Updated: March 6, 2019
• Results First Posted: January 9, 2019

Record last verified: 2019-02

Locations

DE (1)