Freeze-Dried MVA-BN® Lot Consistency Smallpox Trial

NCT03699124 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: POX-MVA-031
• Study Type: interventional
• Target: 1,129
• Locations: 1 country
• Sites: 12

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.

Conditions

Smallpox

Outcome Measures

Primary Outcomes (1)

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

  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.

  Two weeks post second vaccination; approximately Week 6.

Secondary Outcomes (12)

• Vaccinia-Specific Total Antibodies Measured by Enzyme-Linked Immunosorbant Assay (ELISA)

  Two weeks post second vaccination; approximately Week 6.

• 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.

• 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 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.

Study Arms (3)

GP 1: two doses of FD MVA-BN--Lot 1

ACTIVE COMPARATOR

Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 1

Biological: FD MVA-BN

GP 2: two doses of FD MVA-BN--Lot 2

ACTIVE COMPARATOR

Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 2

Biological: FD MVA-BN

GP 3: two doses of FD MVA-BN--Lot 3

ACTIVE COMPARATOR

Healthy, vaccinia-naïve subjects receiving two subcutaneous (SC) vaccinations, four weeks apart with freeze-dried (FD) MVA-BN® - Lot 3

Biological: FD MVA-BN

Interventions

FD MVA-BN BIOLOGICAL

Vaccinations with a 0.5 mL dose of vaccine containing at least 0.5 x 10E8 Infectious Units (Inf.U)

GP 1: two doses of FD MVA-BN--Lot 1; GP 2: two doses of FD MVA-BN--Lot 2; GP 3: two doses of FD MVA-BN--Lot 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Electrocardiogram (ECG) without clinically significant 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, two premature ventricular contractions in a row, ST elevation consistent with ischemia).

You may not qualify if:

• 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.
• History or clinical manifestation of clinically significant and severe hematological, pulmonary, central nervous, cardiovascular or gastrointestinal disorders
• Clinically significant mental disorder not adequately controlled by medical treatment
• History of coronary heart disease, myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor
• Abnormal Troponin I level \> ULN
• Known history of an immediate family member (father, mother, brother, or sister) who has had onset of ischemic heart disease before age 50 years

Sponsors & Collaborators

• Bavarian Nordic: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (12)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Optimal Research, LLC (Synexus)

Melbourne, Florida, 32934, United States

Location

Optimal Research, LLC (Synexus)

Peoria, Illinois, 61614, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kentucky Healthcare Chandler Hospital

Lexington, Kentucky, 40536, United States

Location

Optimal Research, LLC (Synexus)

Rockville, Maryland, 20850, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rochester Clinical Research, Inc.

Rochester, New York, 14609, United States

Location

M3 Wake Research, Inc.

Raleigh, North Carolina, 27612, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Omega Medical Research

Warwick, Rhode Island, 02886, United States

Location

Related Publications (1)

• Turner Overton E, Schmidt D, Vidojkovic S, Menius E, Nopora K, Maclennan J, Weidenthaler H. A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN(R) vaccine in healthy adults. Vaccine. 2023 Jan 9;41(2):397-406. doi: 10.1016/j.vaccine.2022.10.056. Epub 2022 Nov 29.

  PMID: 36460535 DERIVED

MeSH Terms

Conditions

Smallpox

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Limitations and Caveats

There were no limitations on the trial.

Results Point of Contact

• Title: Bavarian Nordic Call Center
• Organization: Bavarian Nordic A/S

medical.information_us@bavarian-nordic.com

1-844-422-8274

Study Officials

• Edgar T Overton, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: October 5, 2018
• First Posted: October 9, 2018
• Study Start: June 19, 2019
• Primary Completion: January 6, 2020
• Study Completion: June 22, 2020
• Last Updated: May 27, 2021
• Results First Posted: May 27, 2021

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)