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)

• ClinicalTrials.gov Identifier: NCT03700242
• Recruitment Status: Completed
• First Posted: October 9, 2018
• Last Update Posted: April 25, 2022
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers (Rabies Immunization)	Biological: HDCV; Biological: PVRV	Phase 3

Detailed Description:

Study duration per participant is approximately 403 to 436 days

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 570 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: September 26, 2018
• Actual Primary Completion Date: January 19, 2019
• Actual Study Completion Date: April 8, 2020

Arms and Interventions

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
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
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: 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
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: Intradermal

Outcome Measures

Primary Outcome Measures :

1. Seroconversion of participant [ Time Frame: 14 days after the last PrEP vaccination ]
   Rabies virus neutralizing antibodies (RVNA) titer ≥ 0.5 IU/mL

Secondary Outcome Measures :

1. Participant RVNA titer [ Time Frame: Day 0 and 14 days after the last PrEP vaccination ]
2. Persistence of RVNA titer [ Time Frame: 6 months and 1 year after the last PrEP vaccination ]
3. Participant RVNA titer after simulated PEP vaccination [ Time Frame: 7 and 14 days after the first simulated PEP vaccination ]
4. Seroconversion of participant [ Time Frame: Day 0 and 14 days after the last PrEP vaccination ]
   RVNA titer ≥ 0.5 IU/mL
5. Persistence of seroconversion [ Time Frame: 6 months and 1 year after the last PrEP vaccination ]
   RVNA titer ≥ 0.5 IU/mL
6. Seroconversion of participant after simulated PEP vaccination - [ Time Frame: 7 and 14 days after the first simulated PEPvaccination ]
   RVNA titer ≥ 0.5 IU/mL
7. Seropositivity of participant [ Time Frame: Day 0 and 14 days after the last PrEP vaccination ]
   RVNA titer ≥ the lower limit of quantitation (LLOQ)
8. Persistence of seropositivity [ Time Frame: 6 months and 1 year after the last PrEP vaccination ]
   RVNA titer ≥ the LLOQ
9. Seropositivity of participant after simulated PEP vaccination [ Time Frame: 7 and 14 days after the first simulated PEP vaccination ]
   RVNA titer ≥ the LLOQ
10. Participant RVNA titer ratios [ Time Frame: 14 days after last PrEP vaccination ]
    Titer 14 days after the last PrEP vaccination / titer at D0
11. Participant RVNA titer ratios (persistence assessment) [ Time Frame: 6 months and 1 year after the last PrEP vaccination ]
    RVNA titer ratios are assessed 6 months / 14 days after the last PrEP vaccination, and 1 year / 14 days after the last PrEP vaccination
12. Participant RVNA titer after simulated PEP vaccination [ Time Frame: 1 year after the last PrEP vaccination ]
    Ratio of titers measured 7 and 14 days after the first simulated PEP vaccination / 1 year after the last PrEP vaccination
13. Solicited injection site and systemic reactions after PrEP vaccination [ Time Frame: 7 days after PrEP vaccination ]
    Injection site reactions: injection site pain, erythema, and swelling. Systemic reactions: fever, headache, malaise and myalgia.
14. Solicited injection site and systemic reactions after simulated PEP vaccination [ Time Frame: 7 days 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Philippines

Investigational Site Number 002

Cebu City, Philippines, 6000

Investigational Site Number 001

Muntinlupa, Philippines, 1770

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi Pasteur, a Sanofi Company

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03700242
• Other Study ID Numbers: VAJ00001; U1111-1216-6210 ( Other Identifier: UTN )
• First Posted: October 9, 2018
• Last Update Posted: April 25, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• 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://vivli.org

• 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

Additional relevant MeSH terms:

Rabies; Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections