Safety, Tolerability and Immunogenicity Study of 3 Prime-boost Regimens for Ebola Vaccines Ad26.ZEBOV/MVA-BN-Filo in Healthy Adults, Children and Human Immunodeficiency Virus Positive (HIV+) Adults

NCT02564523 | Completed Phase 2 Results DMC

• 3 other identifiers: CR107249VAC52150EBL20022019-000690-22
• Study Type: interventional
• Target: 1,075
• Locations: 4 countries
• Sites: 7

Brief Summary

The purpose of this study is to assess the safety, tolerability and immunogenicity of three heterologous prime-boost regimens for Ebola vaccines Ad26.ZEBOV and MVA-BN-Filo. The study will include healthy adults and elderly participants, HIV infected participants and healthy children in 2 age strata.

Conditions

Hemorrhagic Fever, Ebola

Keywords

Healthy; Vaccine; Ebola viruses; Ebola virus disease (EVD); Filoviruses; Hemorrhagic fever; Monovalent vaccine; Human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV); Modified Vaccinia Virus Ankara - Bavarian Nordic (MVA-BN) Filo-vector; Safety; Immunogenicity; Inserm, Centre Muraz

Outcome Measures

Primary Outcomes (17)

• Number of Participants With Adverse Events (Day 29)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

  Up to 28 days post-dose 1 (Day 29)

• Number of Participants With Adverse Events (AEs) (28-Day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

  Up to 28 days post-dose 2 (Day 57 for Cohorts 1, 2a, 2b and 3 [28-Day Interval])

• Number of Participants With Adverse Events (56-day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

  Up 28 days post-dose 2 (Day 85 for Cohorts 1, 2a, 2b and 3 [56-Day Interval])

• Number of Participants With Adverse Events (84-day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

  Up to 28 days post-dose 2 (Day 113 for Cohort 1 [84-Day Interval])

• Number of Participants With Adverse Events Post-dose 3 (Day 393)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

  Up 28 days post-dose 3 (Day 393)

• Number of Participants With Serious Adverse Events

  A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  Up to 3 years and 3 months

• Number of Participants With Immediate Reportable Events (IREs)

  The following neuroinflammatory disorders were considered immediate reportable events which had to be reported to the sponsor within 24 hours of becoming aware of the event. Neuroinflammatory disorders included: cranial nerve disorders including paralyses/paresis (example: bell's palsy), optic neuritis, multiple sclerosis, transverse myelitis, guillain-barre syndrome including miller fisher syndrome, bickerstaff's encephalitis and other variants, acute disseminated encephalomyelitis, including site-specific variants (example: non-infectious encephalitis, encephalomyelitis, myelitis, myeloradiculomyelitis), myasthenia gravis and lambert-eaton myasthenic syndrome, immune-mediated peripheral neuropathies and plexopathies, including chronic inflammatory, demyelinating polyneuropathy, multifocal motor neuropathy, and polyneuropathies associated with monoclonal gammopathy, narcolepsy, isolated paresthesia of more than 7 days duration.

  Up to 3 years and 3 months

• Number of Participants With Solicited Local Adverse Events (Day 8)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

  7 days post-dose 1 (Day 8)

• Number of Participants With Solicited Local Adverse Events (28-day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

  Up to 7 days post-dose 2 (Day 36 for Cohort 1, 2a, 2b and 3 [28-Day Interval])

• Number of Participants With Solicited Local Adverse Events Post-dose 2 (56-day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

  Up to 7 days post-dose 2 (Day 64 for Cohort 1, 2a, 2b and 3 [56-Day Interval])

• Number of Participants With Solicited Local Adverse Events (84-day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

  Up to 7 days post-dose 2 (Day 92 for Cohort 1 [84-Day Interval])

• Number of Participants With Solicited Local Adverse Events (Day 372)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

  Up 7 days post-dose 3 (Day 372)

• Number of Participants With Solicited Systemic Adverse Events (Day 8)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Participants were instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.

  Up to 7 days post-dose 1 (Day 8)

• Number of Participants With Solicited Systemic Adverse Events (28-Day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Participants were instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.

  Up to 7 days post-dose 2 (Day 36 for Cohorts 1, 2a, 2b and 3 [28-Day Interval])

• Number of Participants With Solicited Systemic Adverse Events (56-Day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Participants were instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.

  Up 7 days post-dose 2 (Day 64 for Cohort 1, 2a, 2b and 3 [56-Day Interval])

• Number of Participants With Solicited Systemic Adverse Events (84-Day Interval)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Participants were instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.

  Up 7 days post-dose 2 (Day 92 for Cohort 1 [84-Day Interval])

• Number of Participants With Solicited Systemic Adverse Events (Day 372)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Participants were instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.

  Up to 7 days post-dose 3 (Day 372)

Secondary Outcomes (2)

• Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Filovirus Animal Non-Clinical Group (FANG) Enzyme-linked Immunosorbent Assay

  21-days post-dose 2 (Day 50 for Cohorts 1, 2a, 2b, 3 [28-day interval] , Day 78 for Cohort 1, 2a, 2b, 3 [56-day interval] and Day 106 Cohort 1 [84-day interval]

• Number of Participants With Serious Adverse Events Post-dose 3

  Up 28 days post-dose 3 (Day 393)

Study Arms (3)

Group 1

EXPERIMENTAL

Participants will receive Ad26.ZEBOV, MVA-BN-Filo (Day 1/Day 29) or placebo (Day 1/Day 29) followed by a subset of participants who received Ad26.ZEBOV and MVA-BN-Filo (at selected sites) will receive Ad26.ZEBOV as third vaccination and who received placebo will receive placebo as third vaccination (at least 1 year post prime vaccination).

Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo; Biological: Placebo

Group 2

EXPERIMENTAL

Participants will receive Ad26.ZEBOV, MVA-BN-Filo (Day 1/Day 57) or placebo (Day 1/Day 57) followed by a subset of participants who received Ad26.ZEBOV and MVA-BN-Filo (at selected sites) will receive Ad26.ZEBOV as third vaccination and who received placebo will receive placebo as third vaccination (at least 1 year post prime vaccination).

Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo; Biological: Placebo

Group 3

EXPERIMENTAL

Participants will receive Ad26.ZEBOV, MVA-BN-Filo (Day 1/Day 85) or placebo (Day 1/Day 85)

Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo; Biological: Placebo

Interventions

Ad26.ZEBOV BIOLOGICAL

One 0.5 mL intramuscular (IM) injection of (5x10\*10 viral particles)

Group 1; Group 2; Group 3

MVA-BN-Filo BIOLOGICAL

One 0.5 mL IM injection of (1x10\*8 infectious units)

Group 1; Group 2; Group 3

Placebo BIOLOGICAL

One 0.5 mL IM injection of 0.9% saline

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 4 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Criteria for healthy adults and elderly participants:
• Participant must be healthy in the investigator's clinical judgment on the basis of clinical laboratory tests, medical history, ECG, physical examination and vital signs performed at screening. Participants with hemoglobin values outside the local laboratory reference ranges may be included if the hemoglobin is above the age/gender specific limits
• Female participants of childbearing potential must use adequate birth control measures, must have a negative pregnancy test at screening and immediately prior to each study vaccination
• A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to enrollment, unless a vasectomy was performed more than 1 year prior to screening
• Participant must pass the test of understanding (TOU)
• Participant must be between 18 to 50 years of age and must have a documented HIV-infection for at least 6 months prior to screening
• Parent/legal guardian must pass the TOU before signing the inform consent form. Informed assent must be obtained from adolescents and older children, depending on local regulations and practice
• Pediatric participant's age on the day of randomization must be within one of the 2 age strata: 12-17 years or 4-11 years (all ages inclusive)
• Pediatric participants must have received all routine immunizations appropriate for his or her age as reported by the parent(s)/legal guardian, according to local routine vaccination schedules

You may not qualify if:

• Diagnosed with Ebola virus disease or previously exposed to Ebola virus including travel to epidemic Ebola areas less than 1 month prior to screening
• Having received any candidate Ebola vaccine or any experimental candidate Ad26- or MVA-based vaccine in the past
• Having HIV type 1 or type 2 infection (for healthy adults/elderly/children)
• Pediatric participants with weight-per-height below 10th percentile according to the Centers for Disease Control and Prevention (CDC) growth charts (4- to 11-year-olds)
• A woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study or within at least 3 months after the prime vaccination or up to 1 month after the boost vaccination (whichever takes longer) or within at least 3 months after the third vaccination
• For HIV+ adults, no AIDS-defining illnesses

Sponsors & Collaborators

• Janssen Vaccines & Prevention B.V.: lead
• EBOVAC2 Consortium: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Centre Muraz: collaborator

Study Sites (7)

Unknown Facility

BoboDioulasso, Burkina Faso

Location

Unknown Facility

Ouagadougou, Burkina Faso

Location

Unknown Facility

Abidjan, Côte d’Ivoire

Location

Unknown Facility

Toupah/Ousrou, Côte d’Ivoire

Location

Unknown Facility

Nairobi, Kenya

Location

Unknown Facility

Entebbe, Uganda

Location

Unknown Facility

Kampala, Uganda

Location

Related Publications (3)

• Barry H, Lhomme E, Surenaud M, Nouctara M, Robinson C, Bockstal V, Valea I, Somda S, Tinto H, Meda N, Greenwood B, Thiebaut R, Lacabaratz C. Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. PLoS Negl Trop Dis. 2024 Apr 11;18(4):e0011500. doi: 10.1371/journal.pntd.0011500. eCollection 2024 Apr.

  PMID: 38603720 DERIVED

• Anywaine Z, Barry H, Anzala O, Mutua G, Sirima SB, Eholie S, Kibuuka H, Betard C, Richert L, Lacabaratz C, McElrath MJ, De Rosa SC, Cohen KW, Shukarev G, Katwere M, Robinson C, Gaddah A, Heerwegh D, Bockstal V, Luhn K, Leyssen M, Thiebaut R, Douoguih M; EBL2002 Study group. Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomised, placebo-controlled, multicentre Phase II clinical trial. PLoS Med. 2022 Jan 11;19(1):e1003865. doi: 10.1371/journal.pmed.1003865. eCollection 2022 Jan.

  PMID: 35015777 DERIVED

• Barry H, Mutua G, Kibuuka H, Anywaine Z, Sirima SB, Meda N, Anzala O, Eholie S, Betard C, Richert L, Lacabaratz C, McElrath MJ, De Rosa S, Cohen KW, Shukarev G, Robinson C, Gaddah A, Heerwegh D, Bockstal V, Luhn K, Leyssen M, Douoguih M, Thiebaut R; EBL2002 Study group. Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: A randomised, placebo-controlled Phase II clinical trial in Africa. PLoS Med. 2021 Oct 29;18(10):e1003813. doi: 10.1371/journal.pmed.1003813. eCollection 2021 Oct.

  PMID: 34714820 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola; Hemorrhagic Fevers, Viral

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Limitations and Caveats

A total of 259 participants in Cohort 1 either did not receive dose 2 (N=52) or received dose 2 outside of their protocol-defined interval (N=207), mainly due to the study pause resulting in a reduced precision for the immunogenicity estimates in the Per Protocol Analysis Set.

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Vaccines & Prevention B.V

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Vaccines & Prevention B.V. Clinical Trial

  Janssen Vaccines & Prevention B.V.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2015
• First Posted: September 30, 2015
• Study Start: November 6, 2015
• Primary Completion: February 12, 2019
• Study Completion: February 12, 2019
• Last Updated: March 7, 2022
• Results First Posted: March 7, 2022

Record last verified: 2022-02

Locations

CÔ (2); KE (1); UG (2); BU (2)