Safety, Tolerability and Immunogenicity Study of 2-dose Heterologous Regimens for Ebola Vaccines Ad26.ZEBOV/MVA-BN-Filo

NCT02598388 | Completed Phase 2 Results DMC

• 2 other identifiers: CR108062VAC52150EBL2003
• Study Type: interventional
• Target: 578
• Locations: 6 countries
• Sites: 7

Brief Summary

The purpose of this study is to assess the safety, tolerability and immunogenicity of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as 2-dose heterologous regimens in healthy and in HIV-infected adults.

Conditions

Hemorrhagic Fever, Ebola

Keywords

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

Outcome Measures

Primary Outcomes (14)

• Part 1, Part 2 (Group 2): Number of Participants With Unsolicited Adverse Events

  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited adverse events were events which were reported by the participant voluntarily or obtained by means of interviewing the participant in a nondirected manner at study visits. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  Up to 28 days post each dose (up to Day 43)

• Part 2 (Group 1): Number of Participants With Unsolicited Adverse Events

  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited adverse events were events which were reported by the participant voluntarily or obtained by means of interviewing the participant in a nondirected manner at study visits.

  Up to 28 days post dose 2 visit (up to Day 57)

• Part 1, Part 2 (Group 2): Number of Participants With Serious Adverse Events (SAEs)

  A SAE is an adverse event 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. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  Up to 1 year post dose 2 (up to Day 380)

• Part 2 (Group 1): Number of Participants With SAEs

  A SAE is an adverse event 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 1 year post dose 2 (up to Day 394)

• Part 1, Part 2 (Group 2): Number of Participants With Immediate Reportable Events (IREs)

  The following neuroinflammatory disorders were considered immediate reportable events and which had to be reported to the sponsor within 24 hours of becoming aware of the event: 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 1 year post dose 2 (up to Day 380)

• Part 2 (Group 1): Number of Participants With IREs

  The following neuroinflammatory disorders were considered immediate reportable events and which had to be reported to the sponsor within 24 hours of becoming aware of the event: 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 1 year post dose 2 (up to Day 394)

• Parts 1 and 2: Number of Participants With Solicited Local Adverse Events (AEs) 7 Days Post First Vaccination

  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 first vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  7 days post dose 1 (up to Day 8)

• Part 1, Part 2 (Group 2): Number of Participants With Solicited Local AEs 7 Days Post Second Vaccination

  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 second vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  7 days post dose 2 (up to Day 22)

• Part 2 (Group 1): Number of Participants With Solicited Local AEs 7 Days Post Second Vaccination

  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 second vaccination. Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.

  7 days post dose 2 (up to Day 36)

• Parts 1 and 2: Number of Participants With Solicited Systemic Adverse Events 7 Days Post First Vaccination

  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. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  7 days post dose 1 (up to Day 8)

• Part 1, Part 2 (Group 2): Number of Participants With Solicited Systemic AEs 7 Days Post Second Vaccination

  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. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  7 days post dose 2 (up to Day 22)

• Part 2 (Group 1): Number of Participants With Solicited Systemic AEs 7 Days Post Second Vaccination

  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.

  7 days post dose 2 (up to Day 36)

• Part 1, Part 2 (Group 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 (ELISA)

  GMCs of antibodies binding to EBOV GP using FANG ELISA were reported and were measured in ELISA unit per milliliter (EU/mL). Serum samples were collected for analysis of binding antibodies against EBOV GP using FANG ELISA to determine humoral responses following vaccination. A sample was considered positive, if the value was above the lower limit of quantification (LLOQ), that is, 36.11 ELISA units/mL. As per planned analysis, the data from Parts 1 and 2 (Group 2) of the study was pooled (that is, 14-day interval regimen) and presented separately for the healthy and HIV-infected cohorts.

  21-days post dose 2 (up to Day 36)

• Part 2 (Group 1): GMCs of Binding Antibody Levels Against EBOV GP Measured Using FANG ELISA

  GMCs of antibodies binding to EBOV GP using FANG ELISA were reported and were measured in ELISA unit per milliliter (EU/mL). Serum samples were collected for analysis of binding antibodies against EBOV GP using FANG ELISA to determine humoral responses following vaccination. A sample was considered positive, if the value was above the LLOQ, that is, 36.11 ELISA units/mL.

  21-days post dose 2 (Day 50)

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  Solicited AEs: Up to 7 days post each vaccination (Up to Day 36); Unsolicited AEs: Up to 28 days post each vaccination (Up to Day 57)

Study Arms (3)

Part 1 (US Participants)

EXPERIMENTAL

Participants will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15.

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

Part 2 Group 1 (African Participants)

EXPERIMENTAL

Participants will receive Ad26.ZEBOV or placebo on Day 1 followed by MVA-BN-Filo or placebo on Day 29.

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

Part 2 Group 2 (African Participants)

EXPERIMENTAL

Participants will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15.

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).

Part 1 (US Participants); Part 2 Group 1 (African Participants); Part 2 Group 2 (African Participants)

MVA-BN-Filo BIOLOGICAL

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

Part 1 (US Participants); Part 2 Group 1 (African Participants); Part 2 Group 2 (African Participants)

Placebo BIOLOGICAL

One 0.5 mL IM injection of 0.9 percent (%) saline.

Part 1 (US Participants); Part 2 Group 1 (African Participants); Part 2 Group 2 (African Participants)

Eligibility Criteria

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

You may qualify if:

• Participant must be healthy in the Investigator's clinical judgment on the basis of medical history, physical examination and vital signs performed at Screening
• Participant must be healthy on the basis of clinical laboratory tests and electrocardiogram (ECG) (only in participants \>50 years) performed at Screening. If the results of the laboratory screening tests and ECG are outside the institutional normal reference ranges, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study
• A woman of childbearing potential must have a negative urine β-human chorionic gonadotropin \[beta-hCG\] pregnancy test at Screening and a negative urine \[beta-hCG\] pregnancy test immediately prior to each study vaccine administration
• A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to dose 1 vaccination until at least 3 months after the dose 2 vaccination, unless a vasectomy was performed more than 1 year prior to Screening
• Participant must pass the test of understanding (TOU)

You may not qualify if:

• Has received any candidate Ebola vaccine
• Diagnosed with Ebola virus disease, or prior exposure to EBOV, including travel to epidemic Ebola areas less than 1 month prior to Screening
• Has received any experimental candidate Ad26- or MVA-based vaccine in the past or received any other investigational drug or investigational vaccine or used an invasive investigational medical device within 3 months prior to Screening
• Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products
• Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, other systemic infections) or clinically significant findings during screening of medical history, ECG (only in participants \>50 years), physical examination, vital signs or laboratory testing for which, in the opinion of the investigator, participation would not be in the best interest of the participants (eg, compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments

Sponsors & Collaborators

• Janssen Vaccines & Prevention B.V.: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (7)

Unknown Facility

Silver Spring, Maryland, United States

Location

Unknown Facility

Kericho, Kenya

Location

Unknown Facility

Kisumu, Kenya

Location

Unknown Facility

Maputo, Mozambique

Location

Unknown Facility

Abuja, Nigeria

Location

Unknown Facility

Mbeya, Tanzania

Location

Unknown Facility

Kampala, Uganda

Location

Related Publications (2)

• Ake JA, Paolino K, Hutter JN, Cicatelli SB, Eller LA, Eller MA, Costanzo MC, Paquin-Proulx D, Robb ML, Tran CL, Anova L, Jagodzinski LL, Ward LA, Kilgore N, Rusnak J, Bounds C, Badorrek CS, Hooper JW, Kwilas SA, Ilsbroux I, Anumendem DN, Gaddah A, Shukarev G, Bockstal V, Luhn K, Douoguih M, Robinson C. Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial. Vaccines (Basel). 2024 May 4;12(5):497. doi: 10.3390/vaccines12050497.

  PMID: 38793748 DERIVED

• Mwesigwa B, Sawe F, Oyieko J, Mwakisisile J, Viegas E, Akintunde GA, Kosgei J, Kokogho A, Ntinginya N, Jani I, Shukarev G, Hooper JW, Kwilas SA, Ward LA, Rusnak J, Bounds C, Overman R, Badorrek CS, Eller LA, Eller MA, Polyak CS, Moodley A, Tran CL, Costanzo MC, Leggat DJ, Paquin-Proulx D, Naluyima P, Anumendem DN, Gaddah A, Luhn K, Hendriks J, McLean C, Douoguih M, Kibuuka H, Robb ML, Robinson C, Ake JA. Safety and Immunogenicity of Accelerated Heterologous 2-Dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa. Clin Infect Dis. 2024 Oct 15;79(4):888-900. doi: 10.1093/cid/ciae215.

  PMID: 38657084 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola; Hemorrhagic Fevers, Viral

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: MEDICAL LEADER
• 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: November 4, 2015
• First Posted: November 5, 2015
• Study Start: December 10, 2015
• Primary Completion: December 12, 2018
• Study Completion: December 12, 2018
• Last Updated: February 4, 2025
• Results First Posted: February 18, 2022

Record last verified: 2025-01

Locations

KE (2); MO (1); UG (1); NG (1); US (1); TA (1)