A Safety Trial to Test MVA-BN(R)-Filo and Ad26.ZEBOV Vaccines in Healthy Volunteers

NCT02891980 | Completed Phase 1 FDA Drug

• 1 other identifier: 14-0094
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, double-blind, randomized trial to evaluate the safety and immunogenicity of two heterologous and two homologous prime-boost regimens using MVA-BN(R)-Filo and Ad26.ZEBOV administered in different sequences at Days 1 and 29 in healthy adult subjects aged 18 - 45 years. The study will evaluate the 'omics (transcriptomics, proteomics, lipidomics, metabolomics), antibodies for immunogenicity, CMI, ADCC, and plasmablast responses to MVA-BN(R)-Filo and Ad26.ZEBOV vaccines. The primary objectives of this study are: 1) To assess the safety and reactogenicity of each study group. 2) To assess responses to the study vaccination by study group after the first, second and third dose by transcriptomics. 3) To assess the peak antibody response to the study vaccination by study group to filovirus antigens.

Conditions

Ebola Disease; Marburg Disease

Keywords

Ad26.ZEBOV; Ebola; Immunogenicity; Marburg; MVA-BN-Filo; Omics; Zaire

Outcome Measures

Primary Outcomes (5)

• Determine the differential expression from baseline in mRNA after each study vaccination by study group

  Screening and Days 1, 2, 4, 8, 15, 29, 30, 32, 36, 43, and 57 for Groups 1 and 4; additionally Days 366, 367, 369, 373, 380, 394, and 546 for Groups 2 and 3.

• Determine the number of subjects with a vaccine-related serious adverse event (SAE) from the time of first study vaccination by study group through the duration of the study

  Day 1 through Day 366 in Groups 1 and 4; Day 1 through Day 546 in Groups 2 and 3

• Determine the number of subjects with a vaccine-related unsolicited adverse event (AE) from the time of each study vaccination by study group

  Day 1 through Day 29

• Determine the number of subjects with solicited local and systemic reactogenicity events from the time of study vaccination by study group.

  Day 1 through Day 8

• Determine the peak antibody response against filovirus glycoproteins (GPs) for each study group

  Days 1, 15, 29, 36, 43, 57, 209, and 366 for Groups 1 and 4; additionally Days 369, 373, 380, 394, 546 for Groups 2 and 3.

Secondary Outcomes (2)

• Determine the change in CMI response from baseline against filovirus antigen using peptide pools and measurement by intracellular cytokine staining (ICS) in each of the study groups

  Days 1, 15, 29, 36, 43, 57, 209, and 366 in Groups 1 and 4; additionally Days 369, 373, 380, 394, and 546 in Groups 2 and 3.

• Determine the change in the ADCC from baseline in each of the study groups

  Days 1, 15, 29, 36, 43, 57, 209, and 366 for Groups 1 and 4; additionally Days 373, 380, 394, and 546 for Groups 2 and 3.

Study Arms (4)

Group 2

EXPERIMENTAL

MVA-BN®-Filo Day 1, Ad26.ZEBOV Day 29 and MVA-BN®-Filo Day 366

Biological: Ad26 Zaire Ebola Vaccine; Biological: MVA Multi-Filo Ebola Vaccine

Group 3

EXPERIMENTAL

Ad26.ZEBOV Day 1, MVA-BN®-Filo Day 29 and MVA-BN®-Filo Day 366

Biological: Ad26 Zaire Ebola Vaccine; Biological: MVA Multi-Filo Ebola Vaccine

Group 4

EXPERIMENTAL

Ad26.ZEBOV Day 1, Ad26.ZEBOV Day 29

Biological: Ad26 Zaire Ebola Vaccine

Group1

EXPERIMENTAL

MVA-BN®-Filo Day 1 and MVA-BN®-Filo Day 29

Biological: MVA Multi-Filo Ebola Vaccine

Interventions

Ad26 Zaire Ebola Vaccine BIOLOGICAL

A recombinant adenovirus vector comprising a polynucleotide encoding a filovirus antigenic protein, wherein the recombinant adenovirus vector comprises an adenovirus 26 capsid protein.

Group 2; Group 3; Group 4

MVA Multi-Filo Ebola Vaccine BIOLOGICAL

A multivalent MVA-BN Filovirus vaccine, designed to protect against Ebola Zaire, Ebola Sudan and Marburg virus.

Group 2; Group 3; Group1

Eligibility Criteria

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

You may qualify if:

• Subject must be able to read and provide consent after completing the informed consent process.
• Subject must be able to understand and comply with planned procedures.
• Subject must be a man or woman aged \> / = 18 to \< / = 45 years.
• Subject must have a body mass index (BMI) \> / = 18.5 and \< 35 kg/m\^2.
• Subject must be healthy on the basis of patient-reported medical history, physical examination, and the investigator's clinical judgment.
• Subject must have acceptable laboratory parameters\* within 28 days of enrollment:
• Note 1: If the following acceptable screening laboratory parameters\*\* are out of range, repeat of screening tests is permitted once, provided there is an alternative explanation for the out of range value. The alternative explanation for the out of range value should be documented in the subject's source documents. The acceptable value for repeated screening tests must be available within the 28 days screening period.
• Acceptable laboratory parameters include the following:
• Hemoglobin: women: \> / = 11.5 g/dL; men \> / = 12.5 g/dL
• White blood cell (WBC) count: \> 3.7 Thousand/uL but \< 10.9 Thousand/uL
• Absolute neutrophil count \> 1,500 cells/uL
• Platelets: \> 139 but \< 550 Thousand/uL
• Urinalysis (clean urine sample)\*: protein and blood \< 1+, glucose negative \*Note: for women: in case of menstruation, urinalysis must be postponed, but a result should be available before Day 1.
• Alanine aminotransferase (ALT) \< / = 1 x institutional upper limit of normal
• Serum creatinine \< / = 1 x institutional upper limit of normal

You may not qualify if:

• Has been vaccinated with an Ebola vaccine.
• Has been diagnosed with Ebola disease, or exposed to Ebola including travel to West Africa\* in 2014-2016.
• Note: West Africa includes but is not limited to the countries of Guinea, Liberia, Mali, and Sierra Leone. Subjects who anticipate traveling to epidemic Ebola areas before the end of the study will also be excluded from enrollment into the study.
• Known or suspected receipt of an adenovirus serotype 26 (Ad26)-based vaccine.
• Positive serology for human immunodeficiency virus (HIV)
• Positive Hepatitis B surface antigen
• Positive antibody to Hepatitis C virus (HCV)
• Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products\*.
• \*Note: This includes a known allergy to egg, egg products and aminoglycosides or any of the constituents of the study vaccines \[e.g., polysorbate 80, ethylenediaminetetraacetic acid (EDTA), L-histidine, tris (hydroxymethyl)-amino methane (THAM)).
• Has an acute illness or temperature \> / = 38.0 degrees Celsius within the 3 days prior to Day 1.\* \*Note: Potential subjects can be rescheduled due to acute illness within the 28 day window between screening and enrollment. If acute illness prevents administration of vaccine within the 28 day screening window, the potential subject can be enrolled once the acute illness resolves after repeating safety laboratories and if the subject is otherwise eligible. The ECG does not need to be repeated as it is not a safety laboratory and unlikely to change without clinical event in this age group of volunteers.
• Female subject is pregnant or breast-feeding, or planning to become pregnant while enrolled in the study or within 3 months after the last boost vaccination.
• A history of bleeding or clotting disorders.
• Any clinically significant acute or chronic medical condition\* that, in the opinion of the investigator, would preclude participation.
• E.g., history of seizure disorders, autoimmune disease, immunodeficiency, any spleen disease, active malignancy, active tuberculosis, asthma, or other systemic infections.
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Emory University School of Medicine

Atlanta, Georgia, 30322-1014, United States

Location

Related Publications (1)

• Rostad CA, Yildirim I, Kao C, Yi J, Kamidani S, Peters E, Stephens K, Gibson T, Hsiao HM, Singh K, Spearman P, McCracken C, Agbakoba V, Tomashek KM, Goll JB, Gelber CE, Johnson RA, Lee S, Maner-Smith K, Bosinger S, Ortlund EA, Chen X, Anderson LJ, Wrammert J, Suthar M, Rouphael N, Anderson EJ. A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose. NPJ Vaccines. 2024 Dec 23;9(1):255. doi: 10.1038/s41541-024-01042-4.

  PMID: 39715748 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola; Marburg Virus Disease

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections; Monkey Diseases; Primate Diseases; Animal Diseases

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: September 1, 2016
• First Posted: September 8, 2016
• Study Start: March 24, 2017
• Primary Completion: March 21, 2019
• Study Completion: March 21, 2019
• Last Updated: July 29, 2025

Record last verified: 2017-07-19

Locations

US (1)