Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03965962
Recruitment Status : Recruiting
First Posted : May 29, 2019
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE May 24, 2019
First Posted Date  ICMJE May 29, 2019
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date November 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 21, 2020)
Percentage of participants achieving RVNA titer greater than or equal to (≥) 0.5 IU/mL [ Time Frame: Day 28 ]
RVNA titer will be measured by rapid fluorescent focus inhibition test (RFFIT) assay
Original Primary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
Percentage of participants achieving RVNA titer greater than or equal to (≥) 0.5 IU/mL [ Time Frame: Day 28 post-injection 4 ]
RVNA titer will be measured by rapid fluorescent focus inhibition test (RFFIT) assay
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2020)
  • Number of participants reporting solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days after any vaccination ]
    Injection site reactions: pain, erythema, and swelling Systemic reactions: fever, headache, malaise and myalgia
  • Number of participants reporting immediate adverse events (AEs) [ Time Frame: Within 30 minutes after each vaccination ]
    Medically relevant unsolicited systemic AEs, including those related to the product administered
  • Number of participants reporting unsolicited injection site reactions and systemic AEs [ Time Frame: Within 28 days after each vaccination ]
    Injection site reaction: adverse reaction at and around the injection site considered to be related to the product administered Systemic AEs: systemic manifestations not associated with the vaccination or administration site
  • Number of participants reporting serious adverse events (SAEs) [ Time Frame: Up to 6 months after last vaccination ]
    SAEs, including adverse event of special interest (AESIs)
  • Geometric mean titers (GMTs) of RVNA [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
    RVNA titer will be measured by RFFIT assay
  • Percentage of participants achieving RVNA Titer ≥ 0.5 IU/mL [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
    RVNA titer will be measured by RFFIT assay
  • Percentage of participants with RVNA titer ≥ lower limit of quantitation (LLOQ) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
    RVNA titer will be measured by RFFIT assay LLOQ for RFFIT assay is 0.2 IU/mL
  • Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
    RVNA titer will be measured by RFFIT assay
  • Percentage of participants with complete or incomplete virus neutralization [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
    Virus neutralization is defined as complete (absence of fluorescent cells) or incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
  • Percentage of participants reporting solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days post-vaccination ]
    Injection site reactions: pain, erythema, and swelling Systemic reactions: fever, headache, malaise and myalgia
  • Number of participants reporting immediate adverse events (AEs) [ Time Frame: Within 30 minutes post-vaccination ]
    Medically relevant unsolicited systemic AEs, including those related to the product administered
  • Number of participants reporting unsolicited injection site reactions and systemic AEs [ Time Frame: Within 28 days post-vaccination ]
    Injection site reaction: adverse reaction at and around the injection site considered to be related to the product administered Systemic AEs: systemic manifestations not associated with the vaccination or administration site
  • Number of participants reporting serious adverse events (SAEs) [ Time Frame: Up to 6 months post-vaccination ]
    SAEs, including adverse event of special interest (AESIs)
  • Geometric mean titers (GMTs) of RVNA [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
    RVNA titer will be measured by RFFIT assay
  • Percentage of participants achieving RVNA Titer ≥ 0.5 IU/mL [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
    RVNA titer will be measured by RFFIT assay
  • Percentage of participants with RVNA titer ≥ lower limit of quantitation (LLOQ) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
    RVNA titer will be measured by RFFIT assay LLOQ for RFFIT assay is 0.2 IU/mL
  • Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
    RVNA titer will be measured by RFFIT assay
  • Percentage of participants with complete or incomplete virus neutralization [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
    Virus neutralization is defined as complete (absence of fluorescent cells) or incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults
Official Title  ICMJE Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free in Comparison With Verorab® and Imovax® Rabies, in a Simulated Rabies Post-exposure Regimen in Healthy Adults in France
Brief Summary

Primary Objective:

To demonstrate that Purified Vero Rabies Vaccine - Serum Free Vaccine generation 2 (VRVg-2) is non-inferior to Verorab and Imovax Rabies vaccines when co-administered with human rabies immunoglobulin (HRIG), in terms of proportion of subjects achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 IU/mL at D28, ie, 14 days after the fourth vaccine injection.

Secondary Objective:

  • To describe the safety profile of VRVg-2 versus Verorab and Imovax Rabies vaccines when co-administered with HRIG, as well as that of VRVg-2, after each vaccine injection.
  • To demonstrate that the proportion of subjects in the VRVg-2 + HRIG group achieving an RVNA titer ≥ 0.5 IU/mL at D28 is at least 95%.
  • To describe the immune response induced by VRVg-2 versus Verorab and Imovax Rabies vaccines when co-administered with HRIG, as well as that induced by VRVg-2, at D14 (7 days after the third injection), at D28 (14 days after the fourth injection) and at D42 (14 days after the last injection).
Detailed Description Study duration per participant will be approximately 7 months including: 1 day of screening and vaccination, a 28-day vaccination period, 1 safety-follow up visit at Day 42, 1 safety follow-up/end of study visit at Day 56 and a 6-month safety follow-up call after last vaccine administration.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study is divided into 4 groups: groups 1 to 3 (VRVg-2 + HRIG; Verorab + HRIG; Imovax Rabies + HRIG) are modified double-blind and group 4 (VRVg-2 standalone) is open-label.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Modified double-blind: the participant (or legally acceptable representative) and the Investigator remain unaware of the treatment assignments throughout the study. An unblinded qualified trial staff member will administer the appropriate vaccine but will not be involved in the immunogenicity and safety evaluations.
Primary Purpose: Prevention
Condition  ICMJE Rabies (Healthy Volunteers)
Intervention  ICMJE
  • Biological: VRVg-2

    Pharmaceutical form:Powder and solvent for suspension for injection

    Route of administration: Intramuscular

  • Biological: Purified Vero Rabies Vaccine

    Pharmaceutical form:Powder and solvent for suspension for injection

    Route of administration: Intramuscular

    Other Name: Verorab®
  • Biological: Human Diploid Cell Vaccine (HDCV)

    Pharmaceutical form:Powder and solvent for suspension for injection

    Route of administration: Intramuscular

    Other Name: IMOVAX® Rabies
  • Biological: Rabies immune globulin (human)

    Pharmaceutical form:Solution for injection

    Route of administration: Intramuscular

    Other Name: IMOGAM® Rabies-HT
Study Arms  ICMJE
  • Experimental: Group 1: VRVg-2 + HRIG
    VRVg-2 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28 + Human Rabies Immunoglobulins (HRIG) single injection at Day 0
    Interventions:
    • Biological: VRVg-2
    • Biological: Rabies immune globulin (human)
  • Active Comparator: Group 2: Verorab + HRIG
    Verorab 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28 + HRIG single injection at Day 0
    Interventions:
    • Biological: Purified Vero Rabies Vaccine
    • Biological: Rabies immune globulin (human)
  • Active Comparator: Group 3: Imovax Rabies + HRIG
    Imovax Rabies 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28 + HRIG single injection at Day 0
    Interventions:
    • Biological: Human Diploid Cell Vaccine (HDCV)
    • Biological: Rabies immune globulin (human)
  • Experimental: Group 4: VRVg-2
    VRVg-2 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28
    Intervention: Biological: VRVg-2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 15, 2020)
636
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2019)
504
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date November 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Men or women aged ≥18 years on the day of inclusion (≥ 18 years means from the day of the 18th birthday onwards, with no upper age limit).
  • Able to attend all scheduled visits and to comply with all trial procedures.
  • Body Mass Index (BMI): 18.5 Kg/m2 ≤ BMI ≤ 30 Kg/m2.

Exclusion criteria:

  • Pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile.
  • Participation at the time of study enrollment or, planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
  • Receipt of any vaccine in the 4 weeks (28 days) preceding the first trial vaccination or planned receipt of any vaccine prior to Visit 7.
  • Previous vaccination against rabies (in pre- or post-exposure regimen) with either the trial vaccines or another vaccine.
  • Receipt of immune globulins, blood or blood-derived products in the past 3 months.
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
  • At high risk for rabies exposure during the trial (veterinarians and their staff, animal handlers, rabies researchers, and certain laboratory workers, persons whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other species at risk for having rabies, people travelling where rabies is enzootic).
  • Known systemic hypersensitivity to any of the vaccine or HRIG components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
  • Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination.
  • Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
  • Current alcohol or substance abuse that, in the opinion of the investigator, might interfere with the trial conduct of completion.
  • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
  • Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0 C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
  • Personal history of Guillain-Barré syndrome.
  • Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03965962
Other Study ID Numbers  ICMJE VRV13
2018-004055-20 ( EudraCT Number )
U1111-1216-6151 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi ( Sanofi Pasteur, a Sanofi Company )
Study Sponsor  ICMJE Sanofi Pasteur, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi Pasteur, a Sanofi Company
PRS Account Sanofi
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP