Intradermal Tozinameran for Patients With Immune-mediated Dermatologic Diseases

Immunogenicity and Reactogenicity of Fractionated-dose Intradermal vs Standard Intramuscular Tozinameran as the Fourth Coronavirus Disease 2019 (COVID-19) Vaccine Dose in Patients With Immune-mediated Dermatologic Diseases: a Single-blinded Randomised-controlled Parallel-grouped Non-inferiority Trial

This is a randomised controlled trial conducted to prove that the immunological performance of intradermal tozinameran (i.e., Pfizer-BioNTech COVID-19 vaccine) is no worse than the standard intramuscular route in patients with immune-mediated dermatologic diseases. The side effects profile and disease activity post-vaccination will also be assessed.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Bullous Dermatoses; COVID-19 Vaccines
• Intervention / Treatment: Biological: tozinameran

Detailed Description

The standard intramuscular tozinameran is widely used as a COVID-19 vaccine booster dose, although the fractionated-dose intradermal route of the vaccine has emerged as a dose-sparing and cost-effective alternative. However, before implementing the intradermal vaccine in patients with immune-mediated dermatologic diseases, its immunogenicity should be confirmed, as many of them use long-term immunosuppressive medications, which may alter their immune responses to the vaccine. This prospective open-labelled single-blinded randomised-controlled parallel-grouped non-inferiority trial aims to determine non-inferiority in the immunogenicity of fractionated-dose intradermal tozinameran in comparison with the standard intramuscular tozinameran as the fourth COVID-19 vaccine dose in patients with immune-mediated dermatologic diseases and compare vaccine-related adverse effects between the two.

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chutima Seree-aphinan, MD; Phone Number: (66) 22011211; Email: czircons@gmail.com
• Study Contact Backup: Name: Somsak Tanrattanakorn, MD; Phone Number: (66) 22011211; Email: somsak.rama@gmail.com

Study Locations

• Thailand
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • Dermatology outpatient clinic, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged equal to or more than 18 years
2. Diagnosed with psoriasis or autoimmune bullous diseases
3. Completed two-doses of the primary vaccine series and the third booster dose lasted for more than three months
4. Agree to receive the fourth COVID-19 vaccine dose as tozinameran

Exclusion Criteria:

1. History of previous COVID-19 infection
2. Positive result of COVID-19 rapid antigen test (tested upon recruitment prior to vaccination)
3. Uncontrolled disease activity
4. Non-dermatologic immune-mediated diseases
5. Congenital or acquired immunodeficiency syndrome
6. Cancer
7. Pregnant women
8. Allergy to components of tozinameran
9. Inability to give written informed consent to participate in the study

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: fractionated-dose intradermal tozinameran; 10 micrograms (0.1 mL) of tozinameran administered intradermally to the deltoid area of the non-dominant arm with a sterile 30-gauge needle.	Biological: tozinameran; Pfizer-BioNTech COVID-19 vaccine (Trade name: Comirnaty)
Active Comparator: standard intramuscular tozinameran; 30 micrograms (0.3 mL) of tozinameran administered intramuscularly to the deltoid area of the non-dominant arm with a sterile 25-gauge needle.	Biological: tozinameran; Pfizer-BioNTech COVID-19 vaccine (Trade name: Comirnaty)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline level of humoral immunity at Week 4	Anti-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 Receptor-binding domain (RBD) Immunoglobulin G (IgG)	Week 4
Change from baseline level of cellular immunity at Week 12	Interferon-gamma level from SARS-CoV-2 interferon-gamma release assay (IGRA)	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in the level of SARS-CoV-2 specific humoral immunity between 4- and 12- weeks post-vaccination	Anti-SARS-CoV-2 S1 RBD IgG	Week 4, 12
The difference in the level of SARS-CoV-2 specific humoral immunity between 12- and 24- weeks post-vaccination	Anti-SARS-CoV-2 S1 RBD IgG	Week 12, 24
The difference in the level of SARS-CoV-2 specific cellular immunity between 12- and 24 weeks post-vaccination	IGRA-derived interferon-gamma level	Week 12,24
Vaccine-related adverse reactions	The percentages of participants who have local or systemic vaccine-related adverse reactions	Week 0,1,2,3,4,8,12,24
The changes in the disease activity of psoriasis patients	Psoriasis Area Severity Index (PASI)	Week 0,1,2,3,4,8,12,24
The changes in the disease activity of autoimmune bullous disease patients	Autoimmune Bullous Skin Disorder Intensity Score (ABSIS)	Week 0,1,2,3,4,8,12,24
The changes in the disease activity of pemphigus patients	Pemphigus Disease Area Index (PDAI)	Week 0,1,2,3,4,8,12,24
The changes in the disease activity of bullous pemphigoid patients	Bullous Pemphigoid Disease Area Index (BPDAI)	Week 0,1,2,3,4,8,12,24
Disease control	The percentages of participants who required an adjustment of systemic treatment for disease control	Week 4,12,24
COVID-19	The percentages of participants who are diagnosed with COVID-19 post-vaccination	Any time points during the study period (i.e., up to Week 24)

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Chutima Seree-aphinan, MD, Division of Dermatology, Department of Internal Medicine, Faculty of Medicine Ramathibodi Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: immunogenicity; psoriasis; COVID-19 Vaccine; autoimmune bullous diseases
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Skin Diseases, Papulosquamous; COVID-19; Psoriasis; Skin Diseases; Skin Diseases, Vesiculobullous
• Other Study ID Numbers: MURA2022/238; TCTR20220524004 (Registry Identifier: Thai Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified participant data and study protocol are available from the principle investigators.
• IPD Sharing Time Frame: available without end date
• IPD Sharing Access Criteria: upon reasonable requests made via email.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No