RESIST-3: Immunity Persistence After Abridged Intradermal Rabies PEP

Sponsor

Institut Pasteur (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04829630

Collaborator

Institut Pasteur du Cambodge (Other), Institut Pasteur de Madagascar (Other)

180

Enrollment

Locations

Arm

23.4

Anticipated Duration (Months)

Patients Per Site

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

After exposure, rabies can be prevented in almost 100% of cases by the administration of sufficient and timely post-exposure prophylaxis (PEP). PEP is based on wound cleansing, antisepsis, administration of rabies vaccine as well as rabies immunoglobulin, if reviewed. However, anti-rabies PEP remains too often out of financial and / or geographic access, especially for poor and / or rural populations in endemic countries who remain the most exposed to the risk of contracting rabies. Two major studies planned in Cambodia between 2014 and 2018 - the RESIST 0/1 clinical - epidemiological study and the RESIST-2 study on the antibody response to the vaccine - provided the basis that allowed a change in international recommendations on PPE. Since April 2018, the new "IPC protocol" of three sessions of reduced double doses (0.1 mL x 2) administered intradermally (ID) over one week has replaced the already very effective "TRC protocol" of four sessions over one month which was the reference dose-sparing protocol for endemic countries until 2018. It remains to be determined whether the IPC protocol (3 sessions / 1 week) confers long-term immunity equivalent to that obtained after a TRC ID protocol (4 sessions / 1 month). This question is of importance to public health decision-makers and clinical teams in endemic countries who would hesitate to switch to the abbreviated IPC protocol.

Condition or Disease	Intervention/Treatment	Phase
Rabies	Biological: rabies vaccine	N/A

Detailed Description

This is a multicenter, randomized, non-inferior clinical trial with samples for examinations and vaccination booster.

To achieve this study, persons who previously received PEP and of any age (including children), gender or medical condition (including pregnant women) and whichever the status of the dog which bit at least 2, 5 or 10 years ago will be contacted and invited to participate to the study.

This study will take place in two centers :

The rabies prevention center at Institut Pasteur du Cambodge
The rabies prevention center at Institut Pasteur de Madagascar. The study will be coordinated by Institut Pasteur in Paris which will subsequently conduct the analysis in collaboration with researchers at Institut Pasteur du Cambodge and Institut Pasteur de Madagascar.

This study will take place in two visits :

the first visit (day 0) : after receiving consent from the participants, the member of the investigating team will perform the blood sample, followed by a single session of two intradermal doses of 0.1 mL. The investigators will also carry out measurements and complete the questionnaire with the participant.
the second visit (day 7) : a follow-up visit will be performed by a member of the investigating team who will perform a second blood sample to all the participants to the study. The investigator will complete a second paper CRF with the participants to document any unwanted effects which may have occurred during the seven days between the inclusion visit and the follow-up visit.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

90 subjects in Cambodia or Madagascar who received ID PEP by 3 sessions/1 week at least two (30 subjects), five (30 subjects) or 10 years earlier (30 subjects), 90 subjects in Cambodia or Madagascar who received ID PEP by 4 sessions/1 month at least two (30 subjects), five (30 subjects) or 10 years earlier (30 subjects),90 subjects in Cambodia or Madagascar who received ID PEP by 3 sessions/1 week at least two (30 subjects), five (30 subjects) or 10 years earlier (30 subjects), 90 subjects in Cambodia or Madagascar who received ID PEP by 4 sessions/1 month at least two (30 subjects), five (30 subjects) or 10 years earlier (30 subjects),

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Immunity Persistence After Abridged Intradermal Rabies PEP

Actual Study Start Date :

Oct 20, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: subjects who received three vs. four ID PEP at least two, five or 10 years earlier 30 subjects who received three ID PEP at least two years earlier in Cambodia 30 subjects who received three ID PEP at least five years earlier in Cambodia 30 subjects who received three ID PEP at least 10 years earlier in Cambodia 30 subjects who received four ID PEP at least two years earlier in Madagascar 30 subjects who received four ID PEP at least five years earlier in Madagascar 30 subjects who received four ID PEP at least 10 years earlier in Madagascar	Biological: rabies vaccine day 0 : questionnaire, blood sampling and vaccine booster (a single session of two intradermal doses of 0.1 mL) day 7 : questionnaire and blood sampling

Arm

Intervention/Treatment

Other: subjects who received three vs. four ID PEP at least two, five or 10 years earlier

30 subjects who received three ID PEP at least two years earlier in Cambodia 30 subjects who received three ID PEP at least five years earlier in Cambodia 30 subjects who received three ID PEP at least 10 years earlier in Cambodia 30 subjects who received four ID PEP at least two years earlier in Madagascar 30 subjects who received four ID PEP at least five years earlier in Madagascar 30 subjects who received four ID PEP at least 10 years earlier in Madagascar

Biological: rabies vaccine

day 0 : questionnaire, blood sampling and vaccine booster (a single session of two intradermal doses of 0.1 mL) day 7 : questionnaire and blood sampling

Outcome Measures

Primary Outcome Measures

Antibody titers measured (FAVN, RFFIT) and cellular immunity markers one week after a single session of ID rabies vaccine boosting in the two groups [1 year]
Absence of statistically significant difference between antibody titers Fluorescent Antibody Virus Neutralization test (FAVN) and Rapid Fluorescent Foci Inhibition Test (RFFIT) and cellular immunity markers one week after a single session of ID rabies vaccine boosting in persons who have received a 3 sessions/1 week vs. 4 sessions/ 1 month ID PEP at least 2, 5 or 10 years earlier.

Secondary Outcome Measures

Antibody titers measured by FAVN and RFFIT and immune response before a single session of ID rabies vaccine boosting in the two groups [1 year]
Equivalence of antibody titers and immune response before a single session of ID rabies vaccine boosting in persons who have received a 3 sessions/1 week vs. 4 sessions/ 1 month ID PEP at least 2, 5 or 10 years earlier.
Antibody titers measured by FAVN and RFFIT in all subjects for comparison [1 year]
Equivalence of antibody titers measured using FAVN compared to the RFFIT used as reference.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

person Identified in IP Cambodia or IP Madagascar records for having received ID PEP by 4 sessions/1 month or 3 sessions/1 week at least two, five or 10 years earlier, with no rabies boosting since that time;
person Who received information adapter to his/her age and who signed the consent form (or his/her legal tutors)