Staged Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo (EBOVAC-Salone)

• ClinicalTrials.gov Identifier: NCT02509494
• Recruitment Status: Completed
• First Posted: July 28, 2015
• Last Update Posted: November 4, 2019
• Sponsor: Janssen Vaccines & Prevention B.V.
• Collaborators: London School of Hygiene and Tropical Medicine (LSHTM); Ministry of Health and Sanitation of Sierra Leone; College of Medicine and Allied Health Sciences (COMAHS); University of Oxford; Institut National de la Santé Et de la Recherche Médicale, France; Grameen Foundation; World Vision of Ireland
• Information provided by (Responsible Party): Janssen Vaccines & Prevention B.V.

Tracking Information

• First Submitted Date: June 24, 2015
• First Posted Date: July 28, 2015
• Last Update Posted Date: November 4, 2019
• Actual Study Start Date: September 30, 2015
• Actual Primary Completion Date: June 28, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2019)

• Stage 1: Number of Participants with Adverse Events [ Time Frame: From signing informed consent form (ICF) till 56 days after the Dose 2 vaccination (approximately 156 days) ]
  An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Stage 2: Number of Participants with Adverse Events [ Time Frame: From signing ICF till 28 days post Dose 1 and 28 days post Dose 2 vaccination (approximately 79 days) ]
  An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Stage 1: Number of participants with Serious Adverse Events [ Time Frame: From signing ICF till 36 months post Dose 1 (approximately up to 38 months) ]
  An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
• Stage 2: Number of participants With Serious Adverse Events [ Time Frame: From signing ICF till 2 years post Dose 1 in stage 2 (approximately up to 2 years and 1 month) ]
  An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
• Stage 1 and 2: Number of Participants with Solicited Local and Systemic Adverse Events [ Time Frame: Up to 7 days after each vaccination ]
  Following local AEs: redness of skin, swelling/induration, pain/tenderness, and itching at the injection site will be noted in the participant diary. Following solicited systemic AEs: body temperature, vomiting, reduced activity, somnolence, fatigue, irritability/fussiness/crying/screaming, and loss of appetite for (preverbal children/infants) and body temperature, nausea/vomiting, fatigue/malaise, muscle pain, chills, joint pain and headache (young children, adolescents, and adults) will be noted in the participant diary.

Original Primary Outcome Measures (submitted: July 27, 2015)

• Number of participants With Serious Adverse Events [ Time Frame: Continuous throughout the duration of the study (up to Day 360 ± 1 month) ]
• Number of Participants With Adverse Events [ Time Frame: Up to 56 days post-boost vaccination ]
• Number of Participants with Solicited local and systemic adverse events [ Time Frame: Up to 7 days ]
• Serum concentration of neutralizing antibodies to Ebola virus glycoprotein (EBOV GP) and antibodies binding to EBOV GP [ Time Frame: At day of prime and boost vaccinations, and at day 240 (± 1 month) and Day 360 (± 1 months) ]
  Blood samples will be collected from all subjects from Stage 1 and 2 to assess humoral immune responses to the vaccines over time

• Change History: Complete list of historical versions of study NCT02509494 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 31, 2019)

• Stage 1: Number of Participants with Adverse Events After Booster Vaccination [ Time Frame: From day of booster vaccination till 28 days post booster vaccination (approximately 28 days) ]
  An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Stages 1 and 2: Serum Concentration of Antibodies Binding to EBOV GP Measured by an Enzyme-linked Immunosorbent Assay (ELISA) at 21 Days Post Dose 2 Vaccination [ Time Frame: At 21 days post Dose 2 vaccination ]
  Serum concentration of antibodies binding to ebola virus (EBOV) glycoprotein (GP) measured by an enzyme-linked immunosorbent assay (ELISA) at 21 days post Dose 2 vaccination.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Staged Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo
• Official Title: A Staged Phase 3 Study, Including a Double-Blinded Controlled Stage to Evaluate the Safety and Immunogenicity of Ad26.ZEBOV and MVA-BN-Filo as Candidate Prophylactic Vaccines for Ebola
• Brief Summary: The purpose of this study is the evaluation of the safety and immunogenicity of two candidate Ebola vaccines Ad26.ZEBOV and MVA-BN-Filo, in a 2-dose heterologous regimen.
• Detailed Description: This is staged Phase 3 study to gather information on the safety and immunogenicity of a 2-dose heterologous regimen. In this regimen, Ad26.ZEBOV will be administered as a Dose 1 vaccination followed by the candidate vaccine MVA-BN-Filo (Dose 2 56 days later) and a booster dose of A26.ZEBOV will be administered 2 years post Dose 1 vaccination to participants in Stage 1 who consent to this. The study will take place in Sierra Leone and will consist of a screening phase, an active phase (vaccination) and a follow-up phase. The active phase of the study will be conducted initially in two stages. In the first stage approximately 40 adults aged 18 years or older will be vaccinated to gain information about the safety and immunogenicity of the 2-dose heterologous vaccine regimen. In stage 2 a larger group of approximately 976 individuals will be vaccinated to further evaluate the safety and immunogenicity of the 2 dose heterologous vaccine regimen across different age groups. In this stage, children aged 1 year or older, adolescents and adults will be included. Solicited local and systemic adverse events will be collected until 7 days after the Dose 1 and Dose 2 vaccination. Unsolicited adverse events will be collected from signing of the informed consent form (ICF) onwards until 56 days after the Dose 2 vaccination in Stage 1 and then again from the day of the booster vaccination until 28 days after the booster vaccination, and until 28 days after each vaccination in stage 2. Serious adverse events will be collected from signing of the ICF onwards until 12 and 36 months after the Dose 1 vaccination in Stage 2 and Stage 1, respectively. These data will be reviewed by an independent data monitoring committee (IDMC) to assess whether initiation of vaccination in the next stage or age group can be provided. Safety evaluations will include assessment of adverse events, which will be monitored throughout the study. Participants in Stage 2 will be followed up for safety and immunogenicity until 12 months (children and adolescents) or 24 months (adults) after the Dose 1 vaccination. Participants in Stage 1 will be followed up for safety and immunogenicity until 36 months after the Dose 1 vaccination or until 1 year after the booster vaccination.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Ebola Virus Disease

Intervention

• Biological: Ad26.ZEBOV
  Ebola Zaire vaccine, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles.
• Biological: MVA-BN-Filo
  MVA‐BN‐Filo‐ is a non-replicating vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit (Inf. U.).
• Biological: MenACWY
  MenACWY is a WHO-prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine.
• Biological: Placebo
  0.9% saline for injection.

Study Arms

• Experimental: Stage 1: Active vaccination
  Ad26.ZEBOV will be administered as a 0.5 milliliter (mL) intramuscular (IM) injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2). The booster vaccination using Ad26.ZEBOV will be administered as a 0.5 mL IM injection (2 years post Dose 1).
  Interventions:

  • Biological: Ad26.ZEBOV
  • Biological: MVA-BN-Filo
• Experimental: Stage 2: Active vaccination
  Ad26.ZEBOV will be administered as a 0.5 mL IM injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2).
  Interventions:

  • Biological: Ad26.ZEBOV
  • Biological: MVA-BN-Filo
• Experimental: Stage 2: Active vaccination for children
  Ad26.ZEBOV will be administered as a 0.5 mL IM injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2). Children aged less than 2 years at randomization will receive a booster dose of vaccination at 3 months post Dose 2 with Placebo.
  Interventions:

  • Biological: Ad26.ZEBOV
  • Biological: MVA-BN-Filo
• Active Comparator: Stage 2: Control vaccination
  MenACWY will be administered as a 0.5 mL IM injection on Day 1 (Dose 1) and placebo on Day 57 (Dose 2).
  Interventions:

  • Biological: MenACWY
  • Biological: Placebo
• Active Comparator: Stage 2: Control vaccination for children
  MenACWY will be administered as a 0.5 mL IM injection on Day 1 (Dose 1) and placebo on Day 57 (Dose 2). Children aged less than 2 years at randomization will receive a booster dose of MenACWY vaccination at 3 months post Dose 2 with MenACWY.
  Interventions:

  • Biological: MenACWY
  • Biological: Placebo

• Publications *: Mooney T, Smout E, Leigh B, Greenwood B, Enria L, Ishola D, Manno D, Samai M, Douoguih M, Watson-Jones D. EBOVAC-Salone: Lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country. Clin Trials. 2018 Oct;15(5):436-443. doi: 10.1177/1740774518780678. Epub 2018 Jun 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 14, 2018): 1023
• Original Estimated Enrollment (submitted: July 27, 2015): 440
• Actual Study Completion Date: July 3, 2019
• Actual Primary Completion Date: June 28, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria Stage 1 and 2:

• Documented community engagement from community leader and a signed inform consent form (ICF) from each participant must be available
• Participant Stage 1 must be 18 years or older at screening and be resident in selected study community with no intention to move from study area within the next 5 months
• Participant must be healthy with no abnormalities in laboratory screening tests within 28 days before Dose 1 vaccination
• Female participants of childbearing potential must use adequate birth control measures and must have a negative pregnancy test at screening and immediately prior to each study vaccination
• Participant must pass the test of understanding (TOU)

Additional Inclusion criteria Stage 2:

• One year or older at screening (children of enrolled parents are eligible)
• Parent/legal guardian (for children) must pass the TOU before signing the ICF
• Subjects aged 7 years and older will be asked to give positive assent in the presence of a witness

Exclusion Criteria:

• Diagnosed with EVD or under quarantine/exposed to Ebola or body temperature equal of >= 38 degree Celsius (fever)
• Having an acute illness (mild in nature that can be treated at home) or any clinically significant acute/chronic medical condition or having a decreased number of red blood cells/hemoglobin in the blood (anemia)
• Previously participated in another Ebola interventional study or received any Ad26/MVA-based candidate vaccine
• Vaccinated with live attenuated vaccines within 30 days or with inactivated vaccines 15 days before Dose 1 vaccination
• Treated with an immunosuppressive drug at the time of screening

Additional exclusion criteria:

- Children up to 5 years of age with severe malnutrition (underweight or Z-score weight <2)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sierra Leone

Administrative Information

• NCT Number: NCT02509494
• Other Study ID Numbers: CR107372; VAC52150EBL3001 ( Other Identifier: Janssen Vaccines & Prevention B.V. ); 115854 EBOVAC1 ( Other Grant/Funding Number: The Trial is financed within the IMI-2 Ebola program )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Janssen Vaccines & Prevention B.V.
• Study Sponsor: Janssen Vaccines & Prevention B.V.

Collaborators

• London School of Hygiene and Tropical Medicine (LSHTM)
• Ministry of Health and Sanitation of Sierra Leone
• College of Medicine and Allied Health Sciences (COMAHS)
• University of Oxford
• Institut National de la Santé Et de la Recherche Médicale, France
• Grameen Foundation
• World Vision of Ireland

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial; Janssen Vaccines & Prevention B.V.

• PRS Account: Janssen Vaccines & Prevention B.V.
• Verification Date: October 2019