A Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of MVA-BN Yellow Fever Vaccine With and Without Montanide ISA-720 Adjuvant in 18-45 Year Old Healthy Volunteers

NCT02743455 | Completed Phase 1 FDA Drug

• 2 other identifiers: 14-0107HHSN272201300020I
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a multi-center, double-blind, placebo-controlled, Phase I study to evaluate the safety, reactogenicity, tolerability, and immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) in Flavivirus-naive healthy male and non-pregnant female adult subjects. There are six dose groups in this study. Subjects who have never received a licensed or investigational smallpox vaccine will be randomized to Groups 1-5 and vaccine administration and follow-up will be conducted in a double-blinded fashion. Subjects who have previously received two, 1 x 10\^8 TCID50 doses of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) between 19 and 45 days apart by s ubcutaneous (SC) or intramuscular (IM) routes will be enrolled in Group 6 and will be dosed open-label. Since this is a first in human, phase I study, a sentinel cohort will be utilized. The first two subjects (1st sentinel group) one at each clinical site will be randomized to Group 2 or 3 and vaccinated with MVA-BN-YF with or without Montanide ISA 720 adjuvant (ISA 720). Subjects and study personnel will be blinded as to whether ISA 720 was administered. The primary objectives are the: 1) assessment of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720; 2) comparison of the safety, tolerability, and reactogenicity of MVA-BN-YF vaccine administered with or without ISA 720 with Yellow Fever Vaccine (YF-VAX) and MVA-BN.

Conditions

Yellow Fever; Yellow Fever Immunisation

Keywords

Fever; Immunogenicity; MVA-BN; Reactogenicity; Vaccine; Yellow

Outcome Measures

Primary Outcomes (67)

• Comparison of Grade 3 local, systemic or laboratory toxicities, continuous Grade 2 or greater local reactogenicity

  Day 1 through Day 8

• Comparison of Grade 3 local, systemic or laboratory toxicities, continuous Grade 2 or greater local reactogenicity

  Day 29 through Day 36

• Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 1

  Day 1 through Day 394

• Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 2

  Day 1 through Day 394

• Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 3

  Day 1 through Day 394

• Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 4

  Day 1 through Day 394

• Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 5

  Day 1 through Day 394

• Number of adverse events of special interest (AESIs) considered related to study vaccination in Group 6

  Day 1 through Day 394

• Number of adverse events of special interest (AESIs) considered related to study vaccination overall

  Day 1 through Day 394

• Number of related adverse events of special interest (AESIs)

  Day 1 through Day 394

• Number of related serious adverse events (SAEs)

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination in Group 1

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination in Group 2

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination in Group 3

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination in Group 4

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination in Group 5

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination in Group 6

  Day 1 through Day 394

• Number of serious adverse events (SAEs) considered related to study vaccination overall

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition in Group 1

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition in Group 2

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition in Group 3

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition in Group 4

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition in Group 5

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition in Group 6

  Day 1 through Day 394

• Number of subjects with new onset of a chronic medical condition overall

  Day 1 through Day 394

• Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 1

  Day 1 through Day 57

• Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 2

  Day 1 through Day 57

• Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 3

  Day 1 through Day 57

• Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 4

  Day 1 through Day 57

• Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 5

  Day 1 through Day 57

• Number of subjects with unsolicited vaccine-related adverse events (AEs) in Group 6

  Day 1 through Day 57

• Number of subjects with unsolicited vaccine-related adverse events (AEs) overall

  Day 1 through Day 57

• Number of vaccine-related laboratory adverse events (AEs) in Group 1

  Day 1 through Day 57

• Number of vaccine-related laboratory adverse events (AEs) in Group 2

  Day 1 through Day 57

• Number of vaccine-related laboratory adverse events (AEs) in Group 3

  Day 1 through Day 57

• Number of vaccine-related laboratory adverse events (AEs) in Group 4

  Day 1 through Day 57

• Number of vaccine-related laboratory adverse events (AEs) in Group 5

  Day 1 through Day 57

• Number of vaccine-related laboratory adverse events (AEs) in Group 6

  Day 1 through Day 57

• Number of withdrawals or discontinuation of vaccinations due to any reason

  Day 1 through Day 394

• Occurrence of solicited injection site reactogenicity events in Group 1

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events in Group 1

  Day 29 through Day 36

• Occurrence of solicited injection site reactogenicity events in Group 2

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events in Group 2

  Day 29 through Day 36

• Occurrence of solicited injection site reactogenicity events in Group 3

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events in Group 3

  Day 29 through Day 36

• Occurrence of solicited injection site reactogenicity events in Group 4

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events in Group 4

  Day 29 through Day 36

• Occurrence of solicited injection site reactogenicity events in Group 5

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events in Group 5

  Day 29 through Day 36

• Occurrence of solicited injection site reactogenicity events in Group 6

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events in Group 6

  Day 29 through Day 36

• Occurrence of solicited injection site reactogenicity events overall

  Day 1 through Day 8

• Occurrence of solicited injection site reactogenicity events overall

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events in Group 1

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events in Group 1

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events in Group 2

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events in Group 2

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events in Group 3

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events in Group 3

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events in Group 4

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events in Group 4

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events in Group 5

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events in Group 5

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events in Group 6

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events in Group 6

  Day 29 through Day 36

• Occurrence of solicited systemic reactogenicity events overall

  Day 1 through Day 8

• Occurrence of solicited systemic reactogenicity events overall

  Day 29 through Day 36

Secondary Outcomes (262)

• Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 2

  Day 211

• Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 3

  Day 211

• Comparison of geometric mean titer (GMT) (as measured by ELISA) to MVA-BN between Group 1 and Group 4

  Day 211

• Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 2

  Day 211

• Comparison of geometric mean titer (GMT) (as measured by PRNT) to VACV-WR between Group 1 and Group 3

  Day 211

Study Arms (6)

Group 1

ACTIVE COMPARATOR

Subjects will receive 1.0x10\^8 TCID50 of MVA-BN as two doses subcutaneously on Day 1 and Day 29. N=15

Biological: MVA Smallpox Vaccine

Group 2

EXPERIMENTAL

Subjects will receive 1.0x10\^8 TCID50 of MVA-BN-YF as two doses intramuscularly on Day 1 and Day 29. N=15

Biological: MVA-BN Yellow Fever Vaccine

Group 3

EXPERIMENTAL

Subjects will receive 1.0x10\^8 TCID50 of MVA-BN-YF + ISA 720 as two doses intramuscularly on Day 1 and Day 29. N=15

Drug: ISA-720; Biological: MVA-BN Yellow Fever Vaccine

Group 4

EXPERIMENTAL

Subjects will receive 1.0x10\^8 TCID50 of MVA-BN-YF + ISA 720 as a single dose intramuscularly on Day 1 and matching placebo on Day 29. N=15

Drug: ISA-720; Biological: MVA-BN Yellow Fever Vaccine; Other: Placebo

Group 5

ACTIVE COMPARATOR

Subjects will receive = / \> 4.74 log10 PFU of YF-Vax as a single dose subcutaneously on Day 1 and matching placebo on Day 29. N=15

Other: Placebo; Biological: YF Vax 17D Strain

Group 6

EXPERIMENTAL

Subjects with prior receipt of MVA-BN will receive 1.0x10\^8 TCID50 of MVA-BN-YF as two doses intramuscularly on Day 1 and Day 29. N=15

Biological: MVA-BN Yellow Fever Vaccine

Interventions

ISA-720 DRUG

The vaccine adjuvant ISA 720 will be used with Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) as vaccine adjuvant with a depot effect. This comprises slow release of antigen at the injection site, protection of antigen against degradation and strong stimulation of the immune response.

Group 3; Group 4

MVA Smallpox Vaccine BIOLOGICAL

Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine (MVA BN(R)) is a purified live vaccine will be used as an active comparator.

Group 1

MVA-BN Yellow Fever Vaccine BIOLOGICAL

Modified Vaccinia Ankara-Bavarian Nordic-Yellow Fever (MVA-BN-YF) clinical trial material is manufactured in CEF cells derived from Specific Pathogen Free (SPF) eggs in a bioreactor culture using serum free medium.

Group 2; Group 3; Group 4; Group 6

Placebo OTHER

0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection.

Group 4

YF Vax 17D Strain BIOLOGICAL

Yellow Fever Vaccine (YF-VAX) is a vaccine prepared by culturing the 17D-204 strain of yellow fever virus in living avian leucosis virus-free (ALV-free) chicken embryos. Will be used as an active comparator.

Group 5

Eligibility Criteria

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

You may qualify if:

• Must be a male or female at least 18 to \< / = 45 years old at the time of screening.
• Must be able to read and provide written consent and complete the Informed Consent.
• Must have a body mass index (BMI) \> / = 18.5 and \< 35.0 kg/m\^2.
• Must be in good health on the basis of physical examination, vital signs\*, medical history, safety laboratories, and the investigator's clinical judgment. \*Safety laboratory normal ranges will be those used by the reference clinical lab. Protocol-specific criteria for individual subjects are listed in criteria #6
• The clinical laboratory evaluations that will be graded as laboratory Adverse Events (AEs) and be considered for the Study or Individual Halting Rules are those which are included in the laboratory toxicity grading scales.
• Vital signs must be in normal ranges. If a subject has elevated systolic or diastolic blood pressure, subject may rest for 10 minutes in a quiet room and then the blood pressure may be retaken once.
• For Group 6: subjects must have documented previous vaccination with MVA-BN\*. \*In order to be enrolled, a subject has to have received two 1x10\^8 TCID50 doses of MVA-BN 19-45 days apart subcutaneous (SC) or intramuscular (IM) as part of participation in DMID vaccine trials 11-0021 or 09-0002. First dose must have been administered no earlier than 2010.
• Must have acceptable\* laboratory criteria within 28 days before enrollment.
• \*Acceptable lab parameters include:
• Hemoglobin: women: \> 11.0 g/dL; men \> 12.5 g/dL
• White blood cell count: \> 3,700 cells/mm\^3 but \< 11,000 cells/mm\^3
• Platelets: \> 125,000 but \< 375,000 per mm\^3
• Urine dipstick (clean urine sample): protein \< 1+, glucose negative
• Alanine aminotransferase and aspartate aminotransferase (ALT, AST) \< 1.25 x institutional upper limit of normal
• Blood urea nitrogen (BUN) \< / = 1 x institutional upper limit of normal

You may not qualify if:

• Was ever vaccinated with a licensed or investigational YF vaccine or was diagnosed with YF infection or disease\*.
• \*Includes YF-VAX, Stamaril, or Bio-Manguinhos yellow fever vaccine. Subject's verbal history will suffice.
• Was ever vaccinated with a licensed or investigational Flavivirus vaccine\*.
• \*Including Japanese encephalitis virus (JEV) vaccine or an investigational Flavivirus vaccine including dengue virus (DENV) or West Nile virus vaccine, or has been diagnosed with an illness caused by a Flavivirus including DENV, West Nile virus (WNV), JEV, St. Louis encephalitis, or tick-borne encephalitis virus (TBEV). Subject's verbal history will suffice.
• Positive serology for HIV, Hepatitis C virus, or Hepatitis B surface antigen.
• Positive serology to Dengue, Yellow Fever, or West Nile virus.
• Plans to travel to a Yellow-Fever endemic area during the course of the study\* or travel to a Yellow-Fever endemic area within 30 days of screening.
• \*Subjects who have a recent travel to a Yellow Fever endemic area may screen if they have returned to the U.S. 30 or more days prior to the screening visit. Refer to the CDC Yellow Fever map for countries/regions at risk for Yellow Fever virus infection. http://www.cdc.gov/yellowfever/maps/
• Was ever vaccinated with a licensed or investigational smallpox vaccine\* with the exception of subjects in Group 6.
• \*Includes Dryvax, Acam2000, LC 16 m8, MVA-based vaccine candidate or licensed vaccines, and Imvamune or Imvanex.
• EXCEPTION: Group 6 should have had two 1 x 10\^8 TCID 50 doses of MVA-BN 19-45 days apart SC or IM as part of participation in DMID vaccine trials 11-0021 or 09-0002. First dose must have been administered no earlier than 2010.
• Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products\*.
• \*Including egg products, aminoglycosides, gelatin, sorbitol, tris (hydroxymethyl)-amino methane (THAM), or any of the constituents of the study vaccines.
• Has severe allergy or anaphylaxis to latex\*.
• \*Participants in Group 6 will not be exposed to latex and so may have history of severe allergy or anaphylaxis to latex.

Sponsors & Collaborators

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

Study Sites (2)

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

MeSH Terms

Conditions

Yellow Fever; Fever

Interventions

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 19, 2016
• Study Start: July 5, 2016
• Primary Completion: March 22, 2018
• Study Completion: March 22, 2018
• Last Updated: February 9, 2026

Record last verified: 2019-02-01

Locations

US (2)