Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody

NCT04563923 | Completed Phase 2

• 1 other identifier: 20-PP-13
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

The development of Auto Immune bullous Diseases (AIBD) results from a complex interaction between innate and adaptive immune systems. Bullous pemphigoid (BP), the most frequently encountered AIBD, predominantly affects elderly patients above 70 with an estimated incidence of 21.7 new cases/million/year in France.Interestingly, coversin, an anti-C5a and -leukotriene B4 small molecule, is currently used in a phase IIA clinical trial in BP patients (NCT04035733). However, although overall C5-blocking drugs are potentially interesting, they are likely to interfere with C5a-C5aR2-axis activation as well, a pathway that has recently proved protective in BP 12. The main objective is to investigate the clinical efficacy of an anti-C5aR1 antibody in addition to superpotent topical steroids compared to superpotent topical steroids alone in BP patients at 3 months.It is a case-controlled, randomized, open-labelled, and multicenter phase II clinical trial. Four Dermatologic French centers (Nice, Marseille Nord, Marseille Timone and Montpellier university hospitals) specialized in the in the care of BP patients will be participating in the study. It is expected that forty subjects will be included in this trial. Conversely, a more targeted inhibition of C5a-C5aR1 axis might be more effective in BP, sparing the potentially protective effect of C5a-C5aR2 interaction. Avdoralimab (IPH5401), a specific anti-C5aR1 monoclonal antibody, has already been credited of a good safety profile in the treatment of solid tumors and rheumatoid arthritis. The investigators hypothesize that avdoralimab might be a safe and effective treatment in BP patients

Conditions

Bullous Pemphigoid

Outcome Measures

Primary Outcomes (1)

• Complete Clinical Remission

  To investigate the clinical efficacy of an anti-C5aR1 antibody in addition to superpotent topical steroids compared to superpotent topical steroids alone in BP patients.The efficacy will be evaluated through the proportion of patients in complete clinical remission (CCR) at 3 months without any relapse during the study period. The CCR will be defined as the absence of new bullous and skin inflammatory lesions and absence of pruritus for at least 2 weeks.

  At 3 Months

Secondary Outcomes (2)

• The delay

  At 3 months

• Initial Clinical Remission

  At 3 months

Study Arms (2)

Drug

EXPERIMENTAL

Patients in this group will additionally receive 3 s.c. injections of avdoralimab every week during 12 weeks They receive 0.05% Clobetasol propionate cream as follows: * Patients of less than 45kg of body weight: 2 tubes of 10g/d * Patients of 45kg and above of body weight: 3 tubes of 10g/d Topical steroids will be applied every day until 15 days after the healing of the last bullous lesions

Drug: Avdoralimab (IPH5401)

Conventional therapy

OTHER

Superpotent topical steroids are the gold standard treatment for BP. All patients will receive 0.05% Clobetasol propionate cream as follows: * Patients of less than 45kg of body weight: 2 tubes of 10g/d * Patients of 45kg and above of body weight: 3 tubes of 10g/d Topical steroids will be applied every day until 15 days after the healing of the last bullous lesions

Other: Control

Interventions

Avdoralimab (IPH5401) DRUG

Preparation of avdoralimab and preparation of the syringes are to be performed aseptically by site pharmacy qualified personnel.

Drug

Control OTHER

Superpotent topical steroids are the gold standard treatment for BP. All patients will receive 0.05% Clobetasol propionate cream as follows: * Patients of less than 45kg of body weight: 2 tubes of 10g/d * Patients of 45kg and above of body weight: 3 tubes of 10g/d Topical steroids will be applied every day until 15 days after the healing of the last bullous lesion

Conventional therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• ≥ 18 years of age at the time of signing the informed consent document
• Clinical diagnosis of BP confirmed by histology, immunohistochemistry and/or ELISA data
• Patient requiring a treatment by superpotent topical steroids
• Patients hospitalized for the treatment of their BP
• For female, only post-menopaused patients
• For male patients included in the study with partners of child bearing potential should agree to use highly effective contraception for the duration of the study and 6 months after the last dose of avdoralimab
• Signed informed consent document prior to any study related assessments/procedures being conducted
• Patient able to adhere to the study visit schedule and other protocol requirements
• Patient registered to the French Social Security

You may not qualify if:

• Patients requiring systemic steroids according to the physician in charge
• Contra indication to topical steroid
• Use of systemic steroids or any immunosuppressive drugs in the past 4 weeks
• Use of doxycycline or minocycline in the past 4 weeks
• Use of systemic rituximab or omalizumab or dupilimumab in the past 12 weeks
• Use of intravenous immunoglobulmins (IVIG) in the past 4 weeks
• Impossibility to come every week to receive the injection
• Participants in other clinical therapeutic studies involving a drug that could interfere with the present evaluation
• Vulnerable people: pregnant or breast-feeding women, minors, adult under guardianship or deprived of freedom

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (4)

CHU de Nice- Dermatologie

Nice, Alpes-Maritimes, 06200, France

Location

APHM, Timone

Marseille, Bouche Du Rhône, 13005, France

Location

APHM, Hôpital Nord

Marseille, Bouches du rhône, 13000, France

Location

CHU Montpellier, Dermatologie

Montpellier, Herault, 34005, France

Location

Related Publications (1)

• Passeron T, Fontas E, Boye T, Richard MA, Delaporte E, Dereure O. Treatment of Bullous Pemphigoid with Avdoralimab: Multicenter, Randomized, Open-Labeled Phase 2 Study. JID Innov. 2024 Aug 23;4(6):100307. doi: 10.1016/j.xjidi.2024.100307. eCollection 2024 Nov.

  PMID: 39310808 RESULT

MeSH Terms

Conditions

Pemphigoid, Bullous

Interventions

avdoralimab

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Passeron Thierry, PhD

  CHU de Nice, Dermatologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It is a case-controlled, randomized, open-labelled, and multicenter phase II clinical trial. Four Dermatologic French centers (Nice, Marseille Nord, Marseille Timone and Montpellier university hospitals) specialized in the in the care of BP patients will be participating in the study. It is expected that forty subjects will be included in this trial.

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 25, 2020
• Study Start: October 10, 2020
• Primary Completion: April 30, 2023
• Study Completion: March 31, 2024
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

FR (4)