Clinical trial NCT04563923: Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody
Official title: Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bullous Pemphigoid
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2020-09-25
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Complete Clinical Remission
timeFrame: At 3 Months
Secondary outcomes:
measure: The delay
timeFrame: At 3 months
measure: Initial Clinical Remission
timeFrame: At 3 months
Other outcomes:
Locations:
city: Nice
country: France
facility: CHU de Nice- Dermatologie
state: Alpes-Maritimes
city: Marseille
country: France
facility: APHM, Timone
state: Bouche Du Rhône
city: Marseille
country: France
facility: APHM, Hôpital Nord
state: Bouches Du Rhône
city: Montpellier
country: France
facility: CHU Montpellier, Dermatologie
state: Herault
Study officials:
affiliation: CHU de Nice, Dermatologie
name: Passeron Thierry, PhD
role: PRINCIPAL_INVESTIGATOR
References: