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Trial record 8 of 16 for:    Ad26.ZEBOV

MVA-BN®-Filo and Ad26.ZEBOV Vaccines in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT02891980
Recruitment Status : Not yet recruiting
First Posted : September 8, 2016
Last Update Posted : January 27, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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®-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, lymphoproliferative and plasmablast responses to MVA-BN®-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.

Condition or disease Intervention/treatment Phase
Ebola Disease Marburg Disease Biological: Ad26 Zaire Ebola Vaccine Biological: MVA Multi-Filo Ebola Vaccine Phase 1

Detailed Description:
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®-Filo and Ad26.ZEBOV administered in different sequences at Days 1 and 29 in healthy adult subjects aged 18 - 45 years. The two heterologous prime-boost groups will also receive MVA-BN®-Filo at day 366. Sixty subjects will be randomized 1:1:1:1 to one of four study groups (15 per group).Subjects and study staff will be blinded to a subject's study vaccine assignment within study vaccination schedule (e.g., enrollment into Group 1 or 4 versus 2 or 3 will be known). The study will evaluate the 'omics (transcriptomics, proteomics, lipidomics, metabolomics), antibodies for immunogenicity, CMI, ADCC, lymphoproliferative and plasmablast responses to MVA-BN®-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. Secondary objectives are: 1) To assess antigen-specific cell-mediated immune (CMI) responses to the study vaccination by study group.2) To Assess antibody-dependent cell-mediated cytotoxicity (ADCC) responses to the study vaccination by study group.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: A Phase I Trial to Utilize Systems Biology Approaches to Examine the Safety, Immunogenicity, and 'Omics Response to MVA-BN®-Filo and Ad26.ZEBOV Vaccines in Healthy Volunteers
Estimated Primary Completion Date : January 5, 2018


Arms and Interventions

Arm Intervention/treatment
Experimental: Group 2
MVA-BN®-Filo Day 1, Ad26.ZEBOV Day 29 and MVA-BN®-Filo Day 366
Biological: Ad26 Zaire Ebola Vaccine
A recombinant adenovirus vector comprising a polynucleotide encoding a filovirus antigenic protein, wherein the recombinant adenovirus vector comprises an adenovirus 26 capsid protein.
Biological: MVA Multi-Filo Ebola Vaccine
A multivalent MVA-BN Filovirus vaccine, designed to protect against Ebola Zaire, Ebola Sudan and Marburg virus.
Experimental: Group 3
Ad26.ZEBOV Day 1, MVA-BN®-Filo Day 29 and MVA-BN®-Filo Day 366
Biological: Ad26 Zaire Ebola Vaccine
A recombinant adenovirus vector comprising a polynucleotide encoding a filovirus antigenic protein, wherein the recombinant adenovirus vector comprises an adenovirus 26 capsid protein.
Biological: MVA Multi-Filo Ebola Vaccine
A multivalent MVA-BN Filovirus vaccine, designed to protect against Ebola Zaire, Ebola Sudan and Marburg virus.
Experimental: Group 4
Ad26.ZEBOV Day 1, Ad26.ZEBOV Day 29
Biological: Ad26 Zaire Ebola Vaccine
A recombinant adenovirus vector comprising a polynucleotide encoding a filovirus antigenic protein, wherein the recombinant adenovirus vector comprises an adenovirus 26 capsid protein.
Experimental: Group1
MVA-BN®-Filo Day 1 and MVA-BN®-Filo Day 29
Biological: MVA Multi-Filo Ebola Vaccine
A multivalent MVA-BN Filovirus vaccine, designed to protect against Ebola Zaire, Ebola Sudan and Marburg virus.


Outcome Measures

Primary Outcome Measures :
  1. Determine the differential expression from baseline in mRNA after each study vaccination by study group [ Time Frame: 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. ]
  2. 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 [ Time Frame: Day 1 through Day 366 in Groups 1 and 4; Day 1 through Day 546 in Groups 2 and 3 ]
  3. Determine the number of subjects with a vaccine-related unsolicited adverse event (AE) from the time of each study vaccination by study group [ Time Frame: Day 1 through Day 29 ]
  4. Determine the number of subjects with solicited local and systemic reactogenicity events from the time of study vaccination by study group. [ Time Frame: Day 1 through Day 8 ]
  5. Determine the peak antibody response against filovirus glycoproteins (GPs) for each study group [ Time Frame: 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 Outcome Measures :
  1. 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 [ Time Frame: 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. ]
  2. Determine the change in the ADCC from baseline in each of the study groups [ Time Frame: 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. ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

- 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/m2. - 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. - Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test immediately prior to each study vaccine administration. - Women of childbearing potential must have an acceptable method of contraception* from 28 days before the prime vaccination until at least 3 months after the last boost vaccination. - Female subject agrees to not donate eggs (ova, oocytes) for the purposes of assisted reproduction from the start of screening onwards until at least 3 months after the last boost vaccination. - Male subject who has not had a vasectomy and is sexually active with a woman of childbearing potential must agree to use an acceptable method* of birth control until at least 3 months after the last boost vaccination. - Male subject must also agree not to donate sperm for the purposes of assisted reproduction from the start of screening onwards until at least 3 months after the last boost vaccination. - Subject must be available and willing to participate for the duration of the study visits and follow-up (up to 19 months from enrollment). - Subject must provide identification. - Subject must have a means to be contacted. - Subjects must have consistent access to the internet to perform electronic data entry.

Exclusion Criteria:

-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. - Known or suspected receipt of any licensed or investigational small pox (vaccinia)-based vaccine* Note: Includes any MVA-based candidate vaccine (Imvamune or Imvanex), Dryvax, or Acam2000. Military history should be reviewed with potential subjects for receipt of vaccinia-based vaccine. The presence of a typical vaccinia scar should be considered exclusionary. - 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. - Has an acute illness or temperature >/= 38.0ºC within the 3 days prior to Day 1. - 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. - 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. - Prior organ and/or stem cell transplant. - Major surgery (per the investigator's judgment) within the 4 weeks prior to study entry or planned major surgery through the course of the study. - History of myocarditis, pericarditis, cardiomyopathy, transient ischemic attack or stroke, myocardial infarction, angina, coronary artery disease, congestive heart failure, or arrhythmia. - Electrocardiogram (ECG) with clinically significant findings, or features that would interfere with the assessment of myocarditis/pericarditis. - History of diabetes mellitus type 1 or type 2, including cases controlled with diet alone. - Thyroidectomy or thyroid disease requiring medication during the last 12 months. - Uncontrolled hypertension, defined as systolic blood pressure >/= 140 mmHg or diastolic blood pressure >/= 90 mmHg. Note: Vital signs must be normal by protocol toxicity grading scale or determined to be normal-variant by investigator. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject may rest for 10 minutes in a quiet room, and then blood pressure and/or heart rate may be re-measured. Repeated vital signs may be used to determine eligibility - Received a licensed live vaccine within 30 days prior to enrollment in this study, or plans to receive a licensed live vaccine within 30 days before or after each study vaccine. - Received a licensed inactivated vaccine within 14 days prior to enrollment in this study, or plans to receive a licensed inactivated vaccine within 14 days before or after each study vaccine. - Use of experimental therapeutic agents within 3 months from the start of screening. - Current or planned participation in another clinical study during the study period. - Receipt of blood products or immunoglobulin in the past 3 months. - Donation of a unit of blood within 8 weeks before Day 1 or p lans to donate blood during participation in the study (from the start of screening onwards). - Major psychiatric illness during the past 12 months that in the opinion of the investigator would preclude participation. - Current or past abuse of recreational or narcotic drugs. - Current or past alcohol use judged by the investigator to potentially interfere with subject study adherence. - History of chronic urticaria (recurrent hives). - Chronic or recurrent use of medications which modify host immune response (e.g., cancer chemotherapeutic agents, parenteral corticosteroids). - Subject who cannot communicate reliably with the investigator. - Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study. - Any condition that, in the opinion of the investigator, might interfere with assessing the study objectives. - Personnel involved in the study.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02891980


Contacts
Contact: Mark Mulligan 14047129046 mmulli2@emory.edu

Locations
United States, Georgia
Emory Children's Center - Pediatric Infectious Diseases Not yet recruiting
Atlanta, Georgia, United States, 30322-1014
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02891980     History of Changes
Other Study ID Numbers: 14-0094
HHSN272201300018I
First Posted: September 8, 2016    Key Record Dates
Last Update Posted: January 27, 2017
Last Verified: July 25, 2016

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Ad26
Ebola
immunogenicity response
MVA-Multi Filo
Omics
Zaire

Additional relevant MeSH terms:
Hemorrhagic Fever, Ebola
Marburg Virus Disease
Hemorrhagic Fevers, Viral
RNA Virus Infections
Virus Diseases
Filoviridae Infections
Mononegavirales Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs