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Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers

Primary Purpose

Ebola Virus Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
Guinea
Study Type
Interventional
Intervention
Ervebo
Inmazeb
Sponsored by
ANRS, Emerging Infectious Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ebola Virus Disease focused on measuring Post Exposure Prophylaxis, Ebola vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Available for the duration of the protocol follow-up;
  • Consent to participate ;
  • Agreed not to participate in another clinical research study until the end of the trial follow-up.

Exclusion Criteria:

  • Prior history of EVD (self-reported);
  • Previous vaccination with r-VSV-ZEBOV or any other Ebola vaccine (self-reported);
  • Previous administration of Ebola antibody-based PEP;
  • HIV-1 and/or 2 positive serology;
  • Pregnant women (positive pregnancy test);
  • To the opinion of the investigator, any clinically significant acute/chronic condition that would limit the participant's ability to meet the requirements of the study protocol;
  • Immunosuppressive drugs;
  • Participation in another clinical research study within the last 30 days;
  • Allergy to any component of the vaccine or Mabs;
  • Any other reason that, at the investigator's discretion, would compromise the participant's safety and cooperation in the trial.

Sites / Locations

  • Research center of Landreah

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Single vaccination

Simoultaneous vaccination

Early vaccination

Intermediate vaccination

Late vaccination

Arm Description

The control arm (vaccination alone) will serve as a comparator of vaccine response. r-VSV-ZEBOV vaccine will be administered at inclusion (D0)

Mabs and r-VSV-ZEBOV vaccine will be administered the same day, at inclusion (D0), one hours appart

Mabs are administered at inclusion (D0) and r-VSV-ZEBOV vaccine 3 weeks later

Mabs are administered at inclusion (D0) and r-VSV-ZEBOV vaccine 6 weeks later

Mabs are administered at inclusion (D0) and r-VSV-ZEBOV vaccine 12 weeks later

Outcomes

Primary Outcome Measures

EBOV GP IgG rate at S24 post-vaccination
The primary endpoint was the mean logarithm of the EBOV GP IgG rate at S24 post-vaccination.

Secondary Outcome Measures

VSV viremia
VSV viremia measured by RT-PCR at D2 post-vaccination
EBOV GP IgG rate at W4
Measurement of EBOV GP IgG rate
EBOV GP IgG rate at W12
Measurement of EBOV GP IgG rate
Ratel of neutralizing antibodies at W12 post-vaccination
Measurement of neutralizing antibodies rate measured by sero-neutralization
Ratel of neutralizing antibodies at W24 post-vaccination
Measurement of neutralizing antibodies rate measured by sero-neutralization
Proportion of participants with grade 3 or 4 adverse events 2 days after vaccination
Proportion of participants with grade 3 or 4 adverse events
Proportion of participants with grade 3 or 4 adverse events 4 weeks after vaccination
Proportion of participants with grade 3 or 4 adverse events
Proportion of participants lost to follow-up at W24 after vaccination
Proportion of participants lost to follow-up

Full Information

First Posted
December 15, 2021
Last Updated
January 7, 2022
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Alliance for International Medical Action, University of Bordeaux, Institut National de la Santé Et de la Recherche Médicale, France, Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire, Agence Nationale de Sécurité Sanitaire de Guinée (ANSS), Clinical and Operational Research Alliance (CORAL), Méthodologie et Evaluation pour la Recherche clinique et Epidémiologique sur le VIH en Afrique (MEREVA)
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1. Study Identification

Unique Protocol Identification Number
NCT05202288
Brief Title
Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers
Official Title
Phase IIa Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 2022 (Anticipated)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
March 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Alliance for International Medical Action, University of Bordeaux, Institut National de la Santé Et de la Recherche Médicale, France, Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire, Agence Nationale de Sécurité Sanitaire de Guinée (ANSS), Clinical and Operational Research Alliance (CORAL), Méthodologie et Evaluation pour la Recherche clinique et Epidémiologique sur le VIH en Afrique (MEREVA)

4. Oversight

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.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Ebola virus disease (EVD) is emerging regularly in various African countries for various reasons: during contact with mortal remains, during an unsafe burial or following the viral dissemination around a recovered patient. However, tools to fight the spread of the disease are being made available to countries affected by MVE. A vaccine (Ervebo), developed by the Merck laboratory, demonstrated its efficacy in protecting contacts and contacts of contacts in the "Ebola That's Enough" trial and two monoclonal antibodies (Mabs) have demonstrated their efficacy in reducing mortality in patients with EVM: REGN-E3B and Mab114. The question of their use in post-exposure prophylaxis (PEP), defined as the treatment of contacts at very high risk of contracting EVD, is essential. Vaccination with Ervebo alone does not appear to be a good option for PEP, particularly because antibody synthesis is delayed, and the vaccine is likely to be inactive for 10 days after administration. Monoclonal antibodies, on the other hand, seem to be a promising avenue in this indication because of their rapid action on the inhibition of virus entry into the cell. Moreover, Ervebo vaccine and monoclonal antibodies share the same viral target. It is therefore possible that the vaccine is inhibited by the monoclonal antibodies, particularly in the case of concomitant administration. However, no data on vaccine efficacy in combination are available. The question of the interaction between the monoclonal antibody and Ervebo and the delay between the administration of these two strategies remains unresolved. The hypothesis of this trial is that Ervebo vaccine efficacy is diminished with the concomitant administration of a monoclonal antibody, especially if this administration is close (short time between Mabs and vaccination). We hypothesize that with an optimal delay between Mabs and vaccination, the immunogenicity of the vaccine combined with monoclonal antibodies could be non-inferior to the vaccine alone, thus providing optimal short and long term protection. The primary objective of this study is to compare the vaccine immune response at 24 weeks induced by Ervebo administered on the same day (D0) or at S3, S6, or S12 of Inmazeb administration, in healthy volunteers, with vaccination with Ervebo alone. The trial will have 5 arms. The control arm (vaccination alone) will serve as a comparator of vaccine response in the intervention arms. The 4 intervention arms will assess the minimum time between Mab and vaccination.
Detailed Description
Ebola virus disease (EVD) is emerging regularly in various African countries for various reasons: during contact with mortal remains, during an unsafe burial or following the viral dissemination around a recovered patient. In Guinea, 5 years after the end of the 2014-2016 epidemic that killed 11,000 people, a new epidemic has been declared in the southeast of the country and in Conakry in early 2021. In the Democratic Republic of Congo (DRC), the thirteenth epidemic was declared in early October 2021 in North Kivu province. However, more and more tools to fight the spread of the disease are being made available to countries affected by MVE. During the 2014 West African epidemic, a vaccine (Ervebo), developed by the Merck laboratory, demonstrated its efficacy in protecting contacts and contacts of contacts in the "Ebola That's Enough" trial. This vaccine has since been widely used as part of ring vaccination strategies during the most recent epidemics (2018-2021) in the DRC and the epidemic in Forest Guinea in 2021. In addition, during the tenth DRC epidemic (2018-2020), a compassionate trial (MEURI) and then a randomized controlled therapeutic trial was evaluating 4 molecules (3 passive immunotherapies and 1 direct antiviral) as a specific treatment for EVD. Two monoclonal antibodies (Mabs) have demonstrated their efficacy in reducing mortality in patients with EVD: REGN-E3B and Mab114. With the availability of these management and prevention tools, the question of their use in post-exposure prophylaxis (PEP), defined as the treatment of contacts at very high risk of contracting EVD, is more essential than ever. Indeed, it seems clear that PEP is one of the major axes to be deployed to effectively control EVD. Several PEP strategies have therefore been discussed. Vaccination with Ervebo alone does not appear to be a good option for PEP, particularly because antibody synthesis is delayed, and the vaccine is likely to be inactive for 10 days after administration. On the other hand, monoclonal antobodies seem to be a promising in this indication because of their rapid action on the inhibition of virus entry into the cell or on the virus itself, both in animal models and in humans. However, while monoclonal antibodies are good candidates for PEP, they certainly do not provide sustained immunity. Specifically, in high-risk contacts with EVD, PEP may allow them to avoid the infection associated with that specific contact, but not the persistent risk of infection during the epidemic. Therefore, vaccination is also necessary. Ervebo vaccine and monoclonal antibodies share the same viral target. It is therefore possible that the vaccine is inhibited by the monoclonal antibodies, particularly in the case of concomitant administration. However, no data on vaccine efficacy in combination are available. The question of the interaction between the monoclonal antibody and Ervebo and the delay between the administration of these two strategies remains unresolved. The hypothesis of this trial is that vaccine efficacy is diminished with concomitant administration of a monoclonal antibody, especially if this administration is close (short time between Mabs and vaccination). We hypothesize that with an optimal delay between Mabs and vaccination, the immunogenicity of the vaccine combined with monoclonal antibodies could be non-inferior to that of the vaccine alone, thus providing optimal short and long term protection. The trial will have 5 arms. The control arm (vaccination alone) will serve as a comparator of vaccine response in the intervention arms. The 4 intervention arms will assess the minimum time between Mab and vaccination. From an operational point of view, the ideal solution would be to be able to administer the vaccine at the same time as the Mab (simultaneous arm) or as soon as possible after the Mab is administered. Indeed, when implementing a PEP strategy during an epidemic, delaying vaccination represents a double risk for the patient: i) not being protected between the end of the Mab action and the vaccine and ii) not receiving the vaccine at all due to lack of compliance because of the long delay between contact and vaccination. The early, intermediate and late arms of the IMOVA trial will therefore assess the immunological response when the vaccine is administered 3, 6 or 12 weeks after Mab and thus determine the optimal time between the two interventions. For this purpose, the vaccine response will be analyzed in order to be put in perspective with the acceptable operational delay to guarantee protection and patient compliance. The trial will take place in Guinea, in Conakry during a non-epidemic period for EVD on healthy volunteers. Indeed, it is important that participants in the IMOVA trial are not exposed to Ebola virus during their follow-up, to ensure the absence of potential infection in the late arms in particular. Therefore, if an epidemic were to occur in Guinea, enrollment in the IMOVA trial would be immediately halted and be restarted at the end of the epidemic period. The National Health Research Ethics Committee of Guinea (CNERS) will of course be informed of such a situation

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ebola Virus Disease
Keywords
Post Exposure Prophylaxis, Ebola vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The trial will have 5 arms. The control arm (vaccination alone) will serve as a comparator of vaccine response in the intervention arms. The 4 intervention arms will assess the minimum time between Mab and vaccination. The early, intermediate and late arms of the IMOVA trial will therefore assess the immunological response when the vaccine is administered 3, 6 or 12 weeks after Mab and thus determine the optimal time between the two interventions.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
135 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single vaccination
Arm Type
Active Comparator
Arm Description
The control arm (vaccination alone) will serve as a comparator of vaccine response. r-VSV-ZEBOV vaccine will be administered at inclusion (D0)
Arm Title
Simoultaneous vaccination
Arm Type
Experimental
Arm Description
Mabs and r-VSV-ZEBOV vaccine will be administered the same day, at inclusion (D0), one hours appart
Arm Title
Early vaccination
Arm Type
Experimental
Arm Description
Mabs are administered at inclusion (D0) and r-VSV-ZEBOV vaccine 3 weeks later
Arm Title
Intermediate vaccination
Arm Type
Experimental
Arm Description
Mabs are administered at inclusion (D0) and r-VSV-ZEBOV vaccine 6 weeks later
Arm Title
Late vaccination
Arm Type
Experimental
Arm Description
Mabs are administered at inclusion (D0) and r-VSV-ZEBOV vaccine 12 weeks later
Intervention Type
Biological
Intervention Name(s)
Ervebo
Other Intervention Name(s)
r-VSV-ZEBOV vaccine
Intervention Description
Administration of r-VSV-ZEBOV vaccine
Intervention Type
Drug
Intervention Name(s)
Inmazeb
Other Intervention Name(s)
REGN-E3B
Intervention Description
Administration of Inmazeb
Primary Outcome Measure Information:
Title
EBOV GP IgG rate at S24 post-vaccination
Description
The primary endpoint was the mean logarithm of the EBOV GP IgG rate at S24 post-vaccination.
Time Frame
Week 24 after vaccination
Secondary Outcome Measure Information:
Title
VSV viremia
Description
VSV viremia measured by RT-PCR at D2 post-vaccination
Time Frame
Day 2 after vaccination
Title
EBOV GP IgG rate at W4
Description
Measurement of EBOV GP IgG rate
Time Frame
Week 4 post-vaccination
Title
EBOV GP IgG rate at W12
Description
Measurement of EBOV GP IgG rate
Time Frame
Week 12 after vaccination
Title
Ratel of neutralizing antibodies at W12 post-vaccination
Description
Measurement of neutralizing antibodies rate measured by sero-neutralization
Time Frame
Week 12 after vaccination
Title
Ratel of neutralizing antibodies at W24 post-vaccination
Description
Measurement of neutralizing antibodies rate measured by sero-neutralization
Time Frame
Week 24 after vaccination
Title
Proportion of participants with grade 3 or 4 adverse events 2 days after vaccination
Description
Proportion of participants with grade 3 or 4 adverse events
Time Frame
Day 2 after vaccination
Title
Proportion of participants with grade 3 or 4 adverse events 4 weeks after vaccination
Description
Proportion of participants with grade 3 or 4 adverse events
Time Frame
Week 4 after vaccination
Title
Proportion of participants lost to follow-up at W24 after vaccination
Description
Proportion of participants lost to follow-up
Time Frame
Week 24 after vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Available for the duration of the protocol follow-up; Consent to participate ; Agreed not to participate in another clinical research study until the end of the trial follow-up. Exclusion Criteria: Prior history of EVD (self-reported); Previous vaccination with r-VSV-ZEBOV or any other Ebola vaccine (self-reported); Previous administration of Ebola antibody-based PEP; HIV-1 and/or 2 positive serology; Pregnant women (positive pregnancy test); To the opinion of the investigator, any clinically significant acute/chronic condition that would limit the participant's ability to meet the requirements of the study protocol; Immunosuppressive drugs; Participation in another clinical research study within the last 30 days; Allergy to any component of the vaccine or Mabs; Any other reason that, at the investigator's discretion, would compromise the participant's safety and cooperation in the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marie JASPARD, Dr
Phone
0658809012
Ext
+33
Email
marie.jaspard@coral.alima.ngo
First Name & Middle Initial & Last Name or Official Title & Degree
Alice MONTOYO, Dr
Email
alice.montoyo@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denis MALVY, Pr
Organizational Affiliation
Centre Hospitalier Universitaire de Bordeaux, FRANCE
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Abdoul Habib BEAVOGUI, Dr
Organizational Affiliation
CNFRSR, Maferinyah, Guinée
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research center of Landreah
City
Conakry
Country
Guinea
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abdoul Habib Beavogui, Dr
Phone
628 04 53 52
Ext
+224
Email
bea@maferinyah.org
First Name & Middle Initial & Last Name & Degree
Sayadi SANI, Dr
Email
guinee.cdm@alima.ngo

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers

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