Study of Purified Vero Rabies Vaccine Compared With Two Reference Rabies Vaccines, Given in a Pre-exposure Regimen in Pediatric and Adult Populations and as Single Booster Dose to a Subset of Adults (VRV12)

• ClinicalTrials.gov Identifier: NCT04127786
• Recruitment Status: Completed
• First Posted: October 16, 2019
• Last Update Posted: May 6, 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 this study is:

To demonstrate that VRVg-2 (purified rabies vaccine) is non-inferior to Verorab and Imovax Rabies vaccines in each age group (pediatric and adult populations), in terms of proportion of participants achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 international units (IU)/ milliliter (mL) at Day 42, i.e., 14 days after the last injection.

The secondary objectives of this study are:

• To describe the safety profile of VRVg-2 versus Verorab and Imovax Rabies vaccines after each vaccine injection in each age group.
• To describe the safety of a single booster dose of VRVg-2 in a subset of adults following primary series with VRVg-2, Verorab, and Imovax Rabies vaccine
• To demonstrate that at least 99% of participants in the VRVg-2 group achieve an RVNA titer ≥ 0.5 IU/mL at Day 42.
• To demonstrate that VRVg-2 is non-inferior to Verorab and Imovax Rabies vaccines in each age group, in terms of proportion of participants achieving a RVNA titer of ≥ 0.5 IU/mL at Day 28.
• To describe the immune response induced by VRVg-2 versus Verorab and Imovax Rabies vaccines at Day 28 and Day 42 in all age groups.
• To describe the immune response induced by VRVg-2 at Day 14 after a single booster of VRVg-2 administered 12 months after the primary series with VRVg-2, Verorab or Imovax Rabies vaccines in a subset of adult participants.

Condition or disease	Intervention/treatment	Phase
Rabies (Healthy Volunteers)	Biological: Purified vero rabies vaccine - serum free VRVg-2; Biological: Purified inactivated rabies vaccine (Verorab); Biological: Purified inactivated rabies vaccine (Imovax rabies)	Phase 3

Detailed Description:

The duration of each participant's participation in the study is approximately 7 months (28 day-vaccination period followed by 6 month safety follow-up period). For the subset of adults who receive a single booster dose of VRVg-2, the duration is approximately 18 months (1 booster dose 12 months after the first injection, followed by a 6 month safety follow-up period).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1010 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The study is conducted in an observer-blind manner for all vaccinations. Unblinded staff members, independent of the safety evaluation and other trial evaluations, prepare and administer the vaccine. The Investigator or delegate in charge of safety assessment as well as the participants are blinded and do not know which vaccine is administered.
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free in Comparison With Verorab® and Imovax® Rabies, in a Pre-exposure Regimen in Both Pediatric and Adult Populations and a Single Booster Dose of Purified Vero Rabies Vaccine - Serum Free Administered at 1 Year Post Primary Series in a Subset of Adults in Thailand
• Actual Study Start Date: October 21, 2019
• Actual Primary Completion Date: September 15, 2020
• Actual Study Completion Date: August 22, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1: VRVg-2; VRVg-2, 3 injections at Day 0, Day 7, and Day 28	Biological: Purified vero rabies vaccine - serum free VRVg-2; Pharmaceutical form: Freeze-dried Route of administration: Intramuscular
Active Comparator: Group 2: Verorab; Verorab, 3 injections at Day 0, Day 7, and Day 28	Biological: Purified inactivated rabies vaccine (Verorab); Pharmaceutical form:Freeze-dried Route of administration: Intramuscular
Active Comparator: Group 3: Imovax Rabies; Imovax Rabies, 3 injections at Day 0, Day 7, and Day 28	Biological: Purified inactivated rabies vaccine (Imovax rabies); Pharmaceutical form: Freeze-dried Route of administration: Intramuscular

Outcome Measures

Primary Outcome Measures :

1. Participant with RVNA titer ≥ 0.5 IU/mL [ Time Frame: Day 42 ]
   Percentage of participants with RVNA titer above threshold (≥ 0.5 IU/mL). RVNA titers are measured by the rapid fluorescent focus inhibition test (RFFIT) assay

Secondary Outcome Measures :

1. Number of participants with immediate adverse events [ Time Frame: Within 30 minutes after vaccination ]
   Immediate adverse events include systemic unsolicited adverse events in the 30 minutes after vaccination
2. Number of participants with solicited injection site or systemic reactions [ Time Frame: Within 7 days after vaccination ]
   Injection site reactions are tenderness/pain, erythema, and swelling. Systemic reactions are: in participants aged ˃= 1 year to <=23 months: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability; in participants aged 2 years and above: fever, headache, malaise, and myalgia.
3. Number of participants with unsolicited adverse events [ Time Frame: Within 28 days after vaccination ]
   Unsolicited (spontaneously reported) adverse events are unsolicited injection site reactions occurring within 28 days after each injection and unsolicited systemic adverse events between each injection and up to 28 days after the last injection
4. Number of participants with serious adverse events [ Time Frame: Up to 6 months after last vaccination ]
   Serious adverse events, including adverse events of special interest, are reported throughout the study.
5. RVNA titer [ Time Frame: Day 0, Day 28, Day 42, Month 12, and Month 12 + 14 days ]
   RVNA titers are measured by RFFIT and expressed as geometric mean titers (GMT)
6. RVNA titer ≥ 0.5 IU/mL [ Time Frame: Day 0, Day 28, Day 42, Month 12, and Month 12 + 14 days ]
   Percentage of participants with RVNA titers above threshold (≥ 0.5 IU/mL). RVNA titers are measured by RFFIT
7. RVNA titer above lower limit of quantification [ Time Frame: Day 0, Day 28, Day 42, Month 12, and Month 12 + 14 days ]
   Percentage of participants with RVNA titers above lower limit of quantification are measured by RFFIT
8. RVNA titer ratio [ Time Frame: Day 28 and Day 42 ]
   Individual RVNA titer ratio: Day 28 / Day 0, and Day 42 / Day 0 - 9. Percentage of participants with complete or incomplete neutralization at the dilution of 1/5 in RFFIT.
9. Participant with complete or incomplete neutralization at the starting dilution of the RFFIT assay [ Time Frame: Day 0, Day 28, Day 42, Month 12, and Month 12 + 14 days ]
   Percentage of participants with complete or incomplete neutralization at the dilution of 1/5 in RFFIT.

Eligibility Criteria

• Ages Eligible for Study: 1 Year and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria :

• Aged ≥1 year on the day of inclusion
• Informed consent form has been signed and dated by the participant and /or and the parent(s) or Legally Acceptable Representative and by an independent witness (if required by local regulations), as necessary; and Assent form has been signed and dated by the subject, as required
• Participant (adult ≥ 18 years) or pediatric age group participant (1 year to <18 years) and parent/Legally Acceptable Representative are 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 1 month prior to the first vaccination until 1 month after each vaccination. To be considered of non-childbearing potential, a woman must be pre-menarche or 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 5.
• Previous vaccination against rabies (in pre- or post-exposure regimen) with either the trial vaccines or another vaccine.
• Bite by, or exposure to a potentially rabid animal in the previous 6 months with or without post-exposure prophylaxis.
• 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. Such as veterinarians and their staff, animal handlers, rabies researchers, and certain laboratory workers.
• Known systemic hypersensitivity to any of the study/control 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 intramuscular 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 or substance abuse that, in the opinion of the investigator, might interfere with the trial conduct or 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.

Contacts and Locations

Locations

Thailand

Investigational Site Number 7640001

Bangkok, Thailand, 10330

Investigational Site Number 7640004

Bangkok, Thailand, 10400

Investigational Site Number 7640003

Bangkok, Thailand, 10700

Investigational Site Number 7640002

Khon Kaen, Thailand, 40002

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

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

More Information

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT04127786
• Other Study ID Numbers: VRV12; U1111-1217-3241 ( Other Identifier: UTN )
• First Posted: October 16, 2019
• Last Update Posted: May 6, 2022
• Last Verified: September 2021

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: Yes
• 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; Vaccines; Immunologic Factors; Physiological Effects of Drugs