Safety and Immunogenicity of Purified Verocell Rabies Vaccine PVRV Administered Intramuscularly and Intradermally

An Open-label, Randomized Study Evaluating the Safety and Immunogenicity of the Purified Vero Cell Rabies Vaccine PVRV Administered Intradermally and Intramuscularly as Post-exposure Prophylaxis

Rabies is fatal disease but preventable with rabies vaccines and immunoglobulins, conventionally involves intramuscular (IM) administration of the vaccine. However, switching the intradermal (ID) route offers potential advantages in dosing, time and cost without compromising efficacy and safety. Therefore, this study aims to compare the safety and immunogenicity of a short-term three-doses intradermal regimen (3D-ID) with a conventional five-doses intramuscular regimen (5D-IM) of the purified Vero cell rabies vaccine (PVRV), administered via both intramuscular (IM) and intradermal (ID) routes as post-exposure prophylaxis (PEP).

Study Overview

• Status: Completed
• Conditions: Rabies
• Intervention / Treatment: Biological: PVRV

Detailed Description

Rabies vaccines can be used ID for PEP, according to a WHO Expert Committee recommendation. The administration of short-term PEP through ID (3-doses) offers a safe, immunogenic, dose-sparing, and cost-effective alternative to the conventional protocol (IM, 5-dose regimen) while reducing the volume by up to 60 to 80% and vaccination schedules by 3 weeks. This strategy has the potential to reduce the overall requirement and cost of such vaccines, along with minimizing the burden on healthcare professionals and facilities. Furthermore, this strategy is more likely to improve vaccination compliance compared to conventional protocol, and will certainly improve treatment outcomes.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • KPK
    • Peshawar, KPK, Pakistan, 25000
      • Mohammad Ismail

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants aged 2 year or older
• Both male and female
• Dog-bite cases only
• Informed consent form signed by the individual participant and/or their parents or guardian in case of minor age or major Trauma

Exclusion Criteria:

• Subject is participating in any other clinical trial.
• Pregnant and lactating women
• Have a plan to donate blood while participating in the study
• Received any other vaccine except rabies vaccines in last 6 months

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group-1; 0.2 ml of PVRV Intradermally (ID) on the following days: Day0, Day3, and Day7 Biological: PVRV PEP regimen	Biological: PVRV; Group-1 will receive PVRV ID on on the following days: Day0, Day3, Day7, while group-2 will receive PVRV IM on Day0, Day3, Day7, Day14, and Day28.
Experimental: Group-2; 0.5 ml of PVRV Intramuscularly (IM) on the following days: Day0, Day3, and Day7, Day14 and Day28 Biological: PVRV PEP regimen	Biological: PVRV; Group-1 will receive PVRV ID on on the following days: Day0, Day3, Day7, while group-2 will receive PVRV IM on Day0, Day3, Day7, Day14, and Day28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the clinical efficacy of PVRV administered intradermally vs intramuscularly based on immune response.	Patients were assigned into two groups each consisting of n=50 patients: Group-1 and Group-2. Group-1 were administered PVRV intradermally in a dose of 0.2ml on day 0, day 3, and day 7 as post exposure prophylaxis. While, patients in the group-2 received PVRV intramuscularly in a dose of 0.5ml on day 0, day 3, day 7, day 14 and day 28. Efficacy of PVRV in both groups were measured by the presence of rabies virus neutralizing antibodies (RVNA). Patients with an RVNA titer of ≥ 0.5 IU/mL were considered immunized.	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of PVRV administered intradermally and intramuscularly based on the frequency of adverse drug events	Monitoring of both local and systemic adverse events occurring during the study period The safety of the PVRV was determined by reviewing ADEs obtained during physical examinations following vaccine administration and during follow-up visits in both the groups (group-1 and group-2). The ADEs were recorded after completion of the full vaccination schedule by following-up the patient until day 42. Adverse drug events were characterized in terms of local and systemic effects. A reaction was considered local when it occurred at the site of injection within a few hours of administration, while systemic effects were defined as those occurring in tissues distant from the site of contact between the body and vaccines.	42 days

Collaborators and Investigators

• Sponsor: University of Peshawar
• Collaborators: Hayatabad Medical Complex
• Investigators: Study Chair: Mohammad Ismail, PhD, Department of Pharmacy, University of Peshawar; Study Director: Waqar Ali, MPhil, Department of Pharmacy University of Peshawar

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

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: PVRV-ID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Will be shared on reasonable request from the PI

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