A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000®

NCT01913353 | Completed Phase 3 Results DMC

• 1 other identifier: POX-MVA-006
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 1

Brief Summary

To demonstrate the efficacy of MVA-BN® in terms of vaccinia-specific Plaque Reduction Neutralization Test (PRNT) antibody response and by showing that vaccination prior to administration of ACAM2000® results in an attenuated take.

Conditions

18-42 Year Old Healthy Vaccinia-naïve Subjects

Outcome Measures

Primary Outcomes (2)

• Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits

  GMT based on vaccinia-specific PRNT. Titers below the detection limit are included with a value of 1.

  Day 42 for Group 1 and Day 28 for Group 2

• Maximum Lesion Area (MLA) in mm2 After Scarification With ACAM2000®

  The MLA was defined as the maximum of two measurements: the lesion area measured on Day 6-8 (after scarification) or the lesion area measured on Day 13-15 (after scarification). This was measured using the SilhouetteConnect camera system, and confirmed by the Independent Take Review Committee (ITRC).

  Day 6-8, 13-15 after 3rd Vaccination for Group 1 and Day 6-8, 13-15 after 1st vaccination for Group 2

Secondary Outcomes (22)

• Investigator-measured Maximum Lesion Diameter (MLD) in mm After Scarification With ACAM2000

  Day 6-8 and Day 13-15 after ACAM2000 scarification

• Investigator-measured Lesion Diameter in mm at Day 6-8 After Scarification With ACAM2000

  Day 6-8 after ACAM2000 scarification

• Investigator-measured Lesion Diameter in mm at Day 13-15 After Scarification With ACAM2000

  Day 13-15 after ACAM2000 scarification

• Individual Take as Classified by a Blinded Independent Take Review Committee (ITRC)

  Day 6-8 visit following ACAM2000 vaccination

• Lesion Area in mm2 at Day 6-8 After Scarification With ACAM2000

  Day 6-8 after ACAM2000 scarification

Study Arms (2)

Group 1

EXPERIMENTAL

Two vaccinations; MVA BN ®; administered 4 weeks apart (Day 0 and Day 28) followed by a single vaccination of ACAM2000® vaccine 4 weeks after the second MVA BN® vaccination (Day 56).

Biological: MVA BN®; Biological: ACAM2000®

Group 2

ACTIVE COMPARATOR

A single vaccination of ACAM2000® will be administered at Day 0.

Biological: ACAM2000®

Interventions

MVA BN® BIOLOGICAL

0.5 ml MVA BN® with a nominal titer of 1x10E8 TCID50, administered as a subcutaneous injection

Also known as: IMVAMUNE, IMVANEX

Group 1

ACAM2000® BIOLOGICAL

0.0025 ml ACAM2000®, consisting of 2.5-12.5x10E5 plaque forming units of live vaccinia virus (VACV). Picked up with a bifurcated needle and administered by the percutaneous route (scarification) using 15 jabs of that bifurcated needle.

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects, 18-42 years of age
• The subject has read, signed and dated the Informed Consent, having been advised of the risks and benefits of the trial in a language understood by the subject and prior to performance of any trial specific procedure
• Acceptable medical history by screening evaluation and physical examination
• BMI greater or eaqual than 18.5 and smaller than 35
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening and a negative urine or serum pregnancy test within 24 hours prior to each vaccination
• WOCBP must have used an acceptable method of contraception for 28 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 or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products)
• Human Immunodeficiency Virus (HIV) antibody negative, hepatitis B surface antigen negative and negative antibody test to hepatitis C virus
• White blood cells greater or eaqual than 2500/mm3 and smaller than 11,000/mm3
• Hemoglobin within normal limits
• Platelets greater or eaqual than lower normal limits
• Adequate renal function defined as a calculated Creatinine Clearance (CrCl) greater than 60 ml/min as estimated by the Cockcroft-Gault equation
• Adequate hepatic function in the absence of other evidence of significant liver disease defined as:
• Total bilirubin greater than 1.5 x Upper Limit Normal (ULN)
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) greater than 1.5 x ULN
• Alkaline Phosphatase (Alk Phos) greater than 1.5 x ULN

You may not qualify if:

• Pregnant or breast-feeding women
• Typical vaccinia scar
• Known or suspected history of smallpox vaccination defined as visible vaccination scar or documentation of smallpox vaccination or as reported by the subject
• History of vaccination with any poxvirus-based vaccine
• History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject
• History of or active immunodeficiency or immunosuppression caused by acquired or congenital diseases or caused by ongoing treatments such as chronic (greater than 14 days) high-dose corticosteroids (smaller than 5 mg prednisone \[or equivalent\] per day applied systemically, i.e. parenterally or orally), chronic or planned treatment with steroid eye drops or ointment at time of enrollment or radiation, or immunosuppressive drugs; low-dose corticosteroid topical products and nasal sprays used sporadically, i.e. pro re nata (according to circumstances) are permissible
• Having had radiation or X-ray treatment (not routine X-rays) within the last 3 months
• Post organ and bone-marrow transplant subjects whether or not receiving chronic immunosuppressive therapy
• Eye surgery within 4 weeks prior to trial vaccination
• History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid hormone replacement are not excluded
• Uncontrolled serious infection, i.e. not responding to antimicrobial therapy
• History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous site of cancer
• History of keloid formation
• History or clinical manifestation of severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders
• 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

Sponsors & Collaborators

• Bavarian Nordic: lead
• US Army Medical Research Institute of Infectious Diseases: collaborator

Study Sites (1)

Brian Allgood Army Community Hospital

Seoul, South Korea

Location

Related Publications (1)

• Pittman PR, Hahn M, Lee HS, Koca C, Samy N, Schmidt D, Hornung J, Weidenthaler H, Heery CR, Meyer TPH, Silbernagl G, Maclennan J, Chaplin P. Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox. N Engl J Med. 2019 Nov 14;381(20):1897-1908. doi: 10.1056/NEJMoa1817307.

  PMID: 31722150 DERIVED

MeSH Terms

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic; ACAM2000

Results Point of Contact

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

info@bavarian-nordic.com

+45 3326

Study Officials

• Phillip R Pittman, MD, MPH

  US Army Medical Research Institute of Infectious Diseases

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2013
• First Posted: August 1, 2013
• Study Start: March 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: August 1, 2017
• Last Updated: December 5, 2019
• Results First Posted: December 5, 2019

Record last verified: 2019-11

Locations

KR (1)