A randomized controlled trial to compare the immunogenicity and skin imprinting of intradermal and intramuscular rabies vaccination < RABISKIMM >

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institute Of Tropical Medicine

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

completed 29 Apr 2024

Decision date (initial)

2024-01-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy

To compare the number and proportion of skin-resident memory T cells against RABV (RABV-TRM) after booster dose by vaccination route.

Secondary objectives 6

1. To compare the number and proportion of effector- (RABV-TEM) and central-memory T cells against RABV (RABV-Tcm) after booster dose by vaccination route
2. To compare the rate increase in RABV-TRM, RABV-TEM,RABV-TCM cells after booster vaccination from the primary vaccination, by vaccination route (cf. boostability)
3. To compare the number and proportion of RABV-TRM, RABV-TEM,RABV-TCM cells and their rate of increase by CD4+ and CD8+ T cell differentiation subsets
4. Compare the RABV neutralizing antibody titre (RABV-nAbs) and those with a titre ≥ 3.0 IU/ml (considered to be a proxy for robust protection) and ≥ 10.0 IU/ml at D210+D14 by vaccination route
5. To compare the dynamics in generation and durability of the vaccine-induced, circulating nAbs and (poly-functional) RABV-specific T cell response over time by vaccination route
6. To determine the correlation of the ‘conventional’ RABV-nAb response and the RABV-TEM, RABV-TCM and RABV-TRM responses.

Conditions and MedDRA coding

Rabies

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. MAIN + PILOT + HEALTHY CONTROL GROUP: >/=18 to ≤50 years of age
2. PILOT: Not pregnant or planning to become pregnant during the course of the trial
3. HEALTHY CONTROL GROUP: Able and willing to provide written informed consent
4. HEALTHY CONTROL GROUP: Agreement to share and discuss participant’s medical history and medical records when relevant
5. HEALTHY CONTROL GROUP: No acute illness at time of recruitment
6. MAIN: BMI ≤30 kg/m2
7. MAIN: Agreement to refrain from blood donation and other vaccinations 30 days following each vaccination
8. MAIN: Agreement to share and discuss participant’s medical history and medical records when relevant
9. MAIN: Able and willing to provide written informed consent
10. PILOT: should have had a completed or partly completed schedule of rabies vaccination more than one month prior to recruitment
11. PILOT: BMI ≤30 kg/m2
12. PILOT: Able and willing to provide written informed consent
13. PILOT: No acute illness at time of recruitment
14. MAIN + PILOT: Willing to use contraception during the course of the trial (for women of childbearing potential)

Exclusion criteria 19

1. MAIN + PILOT: Subjects who received a rabies vaccination prior to recruitment (including a single dose)
2. MAIN + PILOT: History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
3. MAIN + PILOT: Any other significant disease, disorder, planned surgery, or finding which may significantly affect the ability of the volunteer to participate in the study or impair interpretation of the study data
4. HEALTHY CONTROL GROUP: Subjects who received a rabies vaccination prior to recruitment (including a single dose)
5. HEALTHY CONTROL GROUP: Receipt of any vaccine (licensed or experimental) within 30 days prior to recruitment
6. HEALTHY CONTROL GROUP: Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer); asplenia; recurrent severe infections and use of immunosuppressant medication within the last 6 months, except topical or short-term oral steroids.
7. HEALTHY CONTROL GROUP: Any other significant disease, disorder, or finding which may significantly affect the ability of the volunteer to participate in the study or impair interpretation of the study data
8. HEALTHY CONTROL GROUP: Suspected or known alcohol or drug dependency
9. MAIN + PILOT: Suspected or known alcohol or drug dependency
10. MAIN + PILOT: Pregnancy or planning to become pregnant during the course of the trial
11. MAIN + PILOT + HEALTHY CONTROL GROUP: Subjects who received PEP (or immunoglobulines)
12. MAIN + PILOT: Receipt of any vaccine (licensed or experimental) within 30 days prior to recruitment
13. MAIN + PILOT: Active participation in another interventional clinical study with active substance intake during the trial or 1 month prior to recruitment
14. MAIN + PILOT: Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer); asplenia; recurrent severe infections and use of immunosuppressant medication within the last 6 months prior to recruitment, except topical or short-term oral steroids.
15. MAIN + PILOT: Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed)
16. MAIN + PILOT: History of anaphylaxis, allergic disease or reactions to any component of the study vaccines
17. HEALTHY CONTROL GROUP: Receipt of any vaccine (licensed or experimental) within 30 days prior to recruitment.
18. MAIN + PILOT : Tendency to keloid (scar) formation in response to skin damage
19. MAIN + PILOT + HEALTHY CONTROL GROUP: Skin diseases at the biopsy and vaccination site

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percentage and absolute number of skin-resident and RABV-specific T cells within the CD3+ lymphocyte parent population after booster vaccination at D120+14, measured by flow cytometry.

Secondary endpoints 6

1. Percentage and absolute number of circulating and RABV-specific TCM and TEM cells within the CD3+ lymphocyte parent population at D120+14
2. Percentage and absolute number of increase in RABV-specific TRM, TCM and TEM cells within the CD3+ lymphocyte parent population from D28 to D120+14
3. Percentage and absolute number of RABV-specific TRM, TCM and TEM CD4+ and CD8+ T cells within the CD3+ lymphocyte parent population at D28 and D120+14, and their percentage and absolute number of increase from D28 to D120+14
4. The geometric mean titres (GMTs) of neutralizing RRFIT test at D210+14
5. The nAbs GMT titres, IFNy+ spot forming units (SFU) and IFNy/TNF-a/IL-2+ SFU at D0, D7, D28, D120, D120+14, D120+90, measured by RRFIT and elispot/fluorospot respectively.
6. At all timepoints, the geometric mean titres (GMTs) of neutralizing RRFIT test and IFNy+ spot forming units (SFU) and IFNy/TNF-a/IL-2+ SFU. In addition at D28 and D120+14, the percentage and absolute number of RABV-specific TRM, TCM and TEM cells within the CD3+ lymphocyte parent population.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institute Of Tropical Medicine

Sponsor organisation

Institute Of Tropical Medicine

Address

Nationalestraat 155

City

Antwerp

Postcode

2000

Country

Belgium

Scientific contact point

Organisation

Institute Of Tropical Medicine

Contact name

Wim Adriaensen

Public contact point

Organisation

Institute Of Tropical Medicine

Contact name

Wim Adriaensen

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications