Study of Purified Vero Rabies Vaccine and Rabies Human Diploid Cell Vaccine in a Simulated Rabies Post-exposure Regimen

Immunogenicity and Safety of the Purified Vero Rabies Vaccine - Serum Free in Comparison With the Rabies Human Diploid Cell Vaccine (Imovax® Rabies) Administered in a Simulated Rabies Post-exposure Regimen in Healthy Adults

The aim of the study is to document the safety and immunogenicity of Purified Vero Rabies Vaccine (VRVg) when given in a simulated post-exposure regimen, i.e. with co-administration of human rabies immunoglobulins (Imovax® Rabies).

Primary Objectives:

• To demonstrate that VRVg is non-inferior to Imovax® Rabies in terms of proportion of subjects achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 international units (IU)/mL at Day 14.
• To demonstrate that the observed proportion of subjects achieving an RVNA titer ≥ 0.5 IU/mL at Day 14 is at least 99%, with a lower limit of the 95% confidence interval (CI) of at least 97%.

Secondary Objectives:

• To assess the clinical safety of each vaccine after each vaccine injection when administered in a simulated post-exposure schedule.
• To describe the geometric mean titer ratio (GMTR) between the 2 vaccine groups at Day 14.

Study Overview

• Status: Completed
• Conditions: Rabies
• Intervention / Treatment: Biological: Imovax® Rabies: inactivated rabies vaccine; Biological: Purified Vero Rabies Vaccine (VRVg)

Detailed Description

All participants will receive five vaccine injections, i.e. one at Day 0, at Day 3, at Day 7, at Day 14 and at Day 28, respectively, (Essen regimen). In addition, human rabies immunoglobulins (HRIG) will be concomitantly administered to all subjects on Day 0.

Safety will be assessed in all participants up to 28 days after vaccination, as applicable, in terms of occurrence of adverse events (AEs), and serious adverse events (SAEs) and adverse events of special interest (AESIs) up to 6 months post-vaccination 5.

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Pembroke Pines, Florida, United States, 33026
    • South Miami, Florida, United States, 33143
  • Idaho
    • Boise, Idaho, United States, 59802
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
  • Utah
    • West Jordan, Utah, United States, 84088

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 to < 65 years on the day of inclusion
• Informed consent form has been signed and dated - Able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria:

• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination)
• 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 preceding the first trial vaccination or planned receipt of any vaccine during the course of the trial
• Previous vaccination against rabies (in pre- or post-exposure regimen) with either the trial vaccine or another vaccine
• Receipt of immunoglobulins, 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)
• Self-reported seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
• At high risk of rabies infection during the trial
• Known systemic hypersensitivity to any of the components of either vaccine or HRIG, 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 IM 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 ≥ 100.4°F). 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Purified Vero Rabies Vaccine Group; Participants will receive the Purified Vero Rabies Vaccine (VRVg)	Biological: Purified Vero Rabies Vaccine (VRVg); 0.5 mL, Intramuscular
Experimental: Imovax® Rabies Vaccine Group; Participants will receive the Imovax® Rabies vaccine	Biological: Imovax® Rabies: inactivated rabies vaccine; 1.0 mL, Intramuscular; Other Names: Imovax® Rabies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 IU/mL at Day 42 (14 days after the last vaccination of primary vaccination series).	Rabies virus neutralizing antibody titer will be determined by the rapid fluorescent focus inhibition test (RFFIT)	Day 14 post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Solicited Injection Site Reactions, Solicited Systemic Reactions, Unsolicited Systemic Reactions, and Serious Adverse Events Occurring Throughout the Trial	Solicited injection site reactions: pain, erythema, and swelling. Solicited systemic reactions: fever (temperature), headache, malaise, and myalgia.	Day 0 up to 6 months post-vaccination
Geometric mean titer ratio (GMTR) following vaccination with either Purified Vero Rabies Vaccine, Serum Free or Rabies Human Diploid Cell Vaccine in a Simulated Rabies Post exposure Regimen	Rabies virus neutralizing antibody titer will be determined by the rapid fluorescent focus inhibition test (RFFIT)	Day 14 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 10, 2013
• First Submitted That Met QC Criteria: June 11, 2013
• First Posted (Estimate): June 13, 2013

Study Record Updates

• Last Update Posted (Estimate): December 3, 2014
• Last Update Submitted That Met QC Criteria: November 17, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Rabies; Purified Vero Rabies Vaccine - Serum Free; Human Diploid Cell Vaccine; Imovax® Rabies
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VRV04; U1111-1117-7447 (Other Identifier: WHO)