Imovax® Rabies and VERORAB® Immunogenicity and Safety After One Week 2-sites Intradermal or 1-site Intramuscular Pre-Exposure Prophylaxis Regimens, Followed by a Simulated Post-Exposure Prophylaxis Regimen at One Year (VAJ00001)

Imovax® Rabies and VERORAB® Immunogenicity and Safety After One Week 2-sites Intradermal or 1-site Intramuscular Pre-Exposure Prophylaxis Regimens, Followed by a Simulated Intradermal or Intramuscular Post-Exposure Prophylaxis Regimen at One Year

The primary objective of the study is to demonstrate that a short intramuscular (IM) pre-exposure prophylaxis (PrEP) regimen is non-inferior to the reference IM PrEP regimen in terms of seroconversion rate.

The secondary objectives of the study are:

• To describe the immunogenicity of the PrEP regimen in each group
• To describe the antibody persistence in each group 6 months and 1 year after the last PrEP vaccination
• To describe the immunogenicity of the simulated post-exposure prophylaxis (PEP) regimen in each group
• To describe the safety profile of study vaccines administered as PrEP regimen and as a simulated PEP regimen in each group

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers (Rabies Immunization)
• Intervention / Treatment: Biological: HDCV; Biological: HDCV; Biological: PVRV; Biological: PVRV

Detailed Description

Study duration per participant is approximately 403 to 436 days

• Study Type: Interventional
• Enrollment (Actual): 570
• Phase: Phase 3

Contacts and Locations

Study Locations

• Philippines
  • Cebu City, Philippines, 6000
    • Investigational Site Number 002
  • Muntinlupa, Philippines, 1770
    • Investigational Site Number 001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Aged ≥ 2 years on the day of inclusion
• Participant aged < 18 years: Assent form has been signed and dated by the subject (as appropriate, according to country-specific institution requirements), and informed consent form (ICF) signed and dated by the parent or another legally acceptable representative
• Participant aged ≥ 18 years: ICF signed and dated by the subject
• The participant (and parent/legally acceptable representative, if applicable) is able to attend all scheduled visits and to comply with all trial procedures

Exclusion criteria:

• Participant is 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 pre-menarche or post-menopausal for at least 1 year, or surgically sterile.
• Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) 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 preceding the first trial vaccination or planned receipt of any vaccine in the 4 weeks following any trial vaccination except for influenza vaccination, which may be received at least 2 weeks before study vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
• Previous vaccination at any time against rabies with either the trial vaccine 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)
• Known systemic hypersensitivity to any of the vaccine 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 IM vaccination
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction
• 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 subject should not be included in the study until the condition has resolved or the febrile event has subsided
• 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 (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
• History of Guillain-Barré syndrome
• Receipt of chloroquine or other medications used for malaria chemoprophylaxis, with or without other anti-malarial treatment, for more than 4 weeks (duration of anti-malarial course) and part of the treatment received within the 2 weeks before vaccination, contraindicating intradermal vaccination

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 1 IM dose of human diploid cell vaccine (HDCV) on D0 and D7 (short HDCV IM PrEP regimen), followed by 1 IM dose of HDCV on Year (Y)1 and Y1 + 3 days	Biological: HDCV; Pharmaceutical form:Solution for injection Route of administration: Intramuscular; Biological: HDCV; Pharmaceutical form:Solution for injection Route of administration: Intradermal
Active Comparator: Group 2; 1 IM dose of HDCV on D0, D7, and D21 (reference), followed by 1 IM dose of HDCV on Y1 and Y1 + 3 days	Biological: HDCV; Pharmaceutical form:Solution for injection Route of administration: Intramuscular; Biological: HDCV; Pharmaceutical form:Solution for injection Route of administration: Intradermal
Experimental: Group 3; 2 intradermal (ID) doses of HDCV on D0 and D7 (short HDCV ID PrEP regimen), followed by 1 ID dose of HDCV on Y1 and Y1 + 3 days	Biological: HDCV; Pharmaceutical form:Solution for injection Route of administration: Intramuscular; Biological: HDCV; Pharmaceutical form:Solution for injection Route of administration: Intradermal
Experimental: Group 4; 1 IM dose of purified Vero cell rabies vaccine (PVRV) on D0 and D7 (short PVRV IM PrEP regimen), followed by 1 IM dose of PVRV on Y1 and Y1 + 3 days	Biological: PVRV; Pharmaceutical form:Solution for injection Route of administration: Intramuscular; Biological: PVRV; Pharmaceutical form:Solution for injection Route of administration: Intradermal
Experimental: Group 5; 2 ID doses of PVRV on D0 and D7 (short PVRV ID PrEP regimen), followed by 1 ID dose of PVRV on Y1 and Y1 + 3 days	Biological: PVRV; Pharmaceutical form:Solution for injection Route of administration: Intramuscular; Biological: PVRV; Pharmaceutical form:Solution for injection Route of administration: Intradermal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion of participant	Rabies virus neutralizing antibodies (RVNA) titer ≥ 0.5 IU/mL	14 days after the last PrEP vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant RVNA titer		Day 0 and 14 days after the last PrEP vaccination
Persistence of RVNA titer		6 months and 1 year after the last PrEP vaccination
Participant RVNA titer after simulated PEP vaccination		7 and 14 days after the first simulated PEP vaccination
Seroconversion of participant	RVNA titer ≥ 0.5 IU/mL	Day 0 and 14 days after the last PrEP vaccination
Persistence of seroconversion	RVNA titer ≥ 0.5 IU/mL	6 months and 1 year after the last PrEP vaccination
Seroconversion of participant after simulated PEP vaccination -	RVNA titer ≥ 0.5 IU/mL	7 and 14 days after the first simulated PEPvaccination
Seropositivity of participant	RVNA titer ≥ the lower limit of quantitation (LLOQ)	Day 0 and 14 days after the last PrEP vaccination
Persistence of seropositivity	RVNA titer ≥ the LLOQ	6 months and 1 year after the last PrEP vaccination
Seropositivity of participant after simulated PEP vaccination	RVNA titer ≥ the LLOQ	7 and 14 days after the first simulated PEP vaccination
Participant RVNA titer ratios	Titer 14 days after the last PrEP vaccination / titer at D0	14 days after last PrEP vaccination
Participant RVNA titer ratios (persistence assessment)	RVNA titer ratios are assessed 6 months / 14 days after the last PrEP vaccination, and 1 year / 14 days after the last PrEP vaccination	6 months and 1 year after the last PrEP vaccination
Participant RVNA titer after simulated PEP vaccination	Ratio of titers measured 7 and 14 days after the first simulated PEP vaccination / 1 year after the last PrEP vaccination	1 year after the last PrEP vaccination
Solicited injection site and systemic reactions after PrEP vaccination	Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia.	7 days after PrEP vaccination
Solicited injection site and systemic reactions after simulated PEP vaccination	Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia. Solicited systemic reactions are collected between the first and second PEP injection and within 7 days after the second PEP injection.	7 days after simulated PEP vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Quiambao BP, Lim JG, Bosch Castells V, Augard C, Petit C, Bravo C, Delore V, Houillon G. One-week intramuscular or intradermal pre-exposure prophylaxis with human diploid cell vaccine or Vero cell rabies vaccine, followed by simulated post-exposure prophylaxis at one year: A phase III, open-label, randomized, controlled trial to assess immunogenicity and safety. Vaccine. 2022 Aug 26;40(36):5347-5355. doi: 10.1016/j.vaccine.2022.07.037. Epub 2022 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): January 19, 2019
• Study Completion (Actual): April 8, 2020

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies
• Other Study ID Numbers: VAJ00001; U1111-1216-6210 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No