Clinical trial NCT03700242: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy Volunteers (Rabies Immunization)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-10-09
Enrollment: 570
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed description: Study duration per participant is approximately 403 to 436 days

Eligibility 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.

Primary outcomes:
measure: Seroconversion of participant
timeFrame: 14 days after the last PrEP vaccination
Secondary outcomes:
measure: Participant RVNA titer
timeFrame: Day 0 and 14 days after the last PrEP vaccination
measure: Persistence of RVNA titer
timeFrame: 6 months and 1 year after the last PrEP vaccination
measure: Participant RVNA titer after simulated PEP vaccination
timeFrame: 7 and 14 days after the first simulated PEP vaccination
measure: Seroconversion of participant
timeFrame: Day 0 and 14 days after the last PrEP vaccination
measure: Persistence of seroconversion
timeFrame: 6 months and 1 year after the last PrEP vaccination
measure: Seroconversion of participant after simulated PEP vaccination -
timeFrame: 7 and 14 days after the first simulated PEPvaccination
measure: Seropositivity of participant
timeFrame: Day 0 and 14 days after the last PrEP vaccination
measure: Persistence of seropositivity
timeFrame: 6 months and 1 year after the last PrEP vaccination
measure: Seropositivity of participant after simulated PEP vaccination
timeFrame: 7 and 14 days after the first simulated PEP vaccination
measure: Participant RVNA titer ratios
timeFrame: 14 days after last PrEP vaccination
measure: Participant RVNA titer ratios (persistence assessment)
timeFrame: 6 months and 1 year after the last PrEP vaccination
measure: Participant RVNA titer after simulated PEP vaccination
timeFrame: 1 year after the last PrEP vaccination
measure: Solicited injection site and systemic reactions after PrEP vaccination
timeFrame: 7 days after PrEP vaccination
measure: Solicited injection site and systemic reactions after simulated PEP vaccination
timeFrame: 7 days after simulated PEP vaccination
Other outcomes:
Locations:
city: Cebu City
country: Philippines
facility: Investigational Site Number 002
city: Muntinlupa
country: Philippines
facility: Investigational Site Number 001
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.