Phase III Trial to Investigate Efficacy and Safety of Vilobelimab in Ulcerative Pyoderma Gangrenosum

Study Overview
=================
Brief Summary
-----------------
A randomized, double-blind, placebo-controlled, multicenter, adaptive phase III trial to investigate efficacy and safety of vilobelimab in the treatment of ulcerative pyoderma gangrenosum

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Multicenter, Adaptive Phase III Trial to Investigate Efficacy and Safety of Vilobelimab in the Treatment of Ulcerative Pyoderma Gangrenosum

Conditions
-----------------
Pyoderma Gangrenosum

Intervention / Treatment
-----------------
* Drug: vilobelimab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: 18 years or older at the time of signing the informed consent. Investigator confirmed clinical diagnosis of ulcerative PG. Diagnosis shall be supported by clinical assessment of PG symptoms via PARACELSUS score (Jockenhofer, Wollina et al. 2019) of 10 points or more (see Appendix - Section 12.1). Note: in case of PARACELSUS score < 10, additional justification shall be provided by the investigator to support clinical diagnosis of ulcerative PG. Minimum of 1 evaluable PG ulcer (other than peristomal) which qualifies as the target ulcer by meeting the following criteria (Orfaly, Reese et al. 2022): area of ≥ 5 cm 2 at screening and baseline circulated by intact skin evaluable by at least 2-dimensional measurement Main Exclusion Criteria: Patients with target ulcers exceeding 80 cm 2 . Patients with target ulcer in transplanted skin. Surgical wound debridement or negative pressure wound therapy (NPWT) for the target ulcer within 4 weeks before baseline (i.e., start of treatment with IMP). Patient with previous exposure to vilobelimab (IFX-1) prior to baseline (i.e., start of treatment with IMP). Patient receives/has received a vaccine within 2 weeks prior to baseline (i.e., start of treatment with IMP). Any active infection requiring systemic antibiotic or other systemic treatment or suppressive anti-infective therapy within 2 weeks prior to baseline (i.e., start of treatment with IMP). Patients received any systemic medical treatment for PG within 4 weeks prior to baseline Patients received any biological or immunomodulatory therapy for PG within 4 weeks prior to baseline (i.e., start of treatment with IMP), except existing biologic or immunomodulatory therapy used for an underlying disease (other than PG at a stable therapy with no dose adjustments for at least two maintenance doses prior to screening this is allowed to be continued. Patients receiving corticosteroids treatment for PG of more than 10 mg/day of prednisone or equivalent within 4 weeks prior to baseline (i.e., start of treatment with IMP).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vilobelimab<br>Patients will be treated with vilobelimab IV, Q2W for 26 weeks | Drug: vilobelimab<br>* vilobelimab infusion<br>|
| Placebo Comparator: Placebo<br>Patients will receive placebo IV in the same schedule as patients in Arm 1 | Drug: Placebo<br>* Placebo Infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of treatment with vilobelimab compared to placebo | Efficacy of Vilobelimab compared to placebo - complete closure of the ulcer | Week 1 to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of treatment with vilobelimab compared to placebo | Proportion of patients achieving disease remission up to and including EOT visit; where disease remission is assessed by the investigator as complete re-epithelization (defined as wound covered by epithelial skin layer or scar) of all PG ulcers, without drainage or dressing requirements | 2 weeks between study visits | 
| Pain reduction | Proportion of patients achieving a pain reduction related to the target ulcer of at least 3 points compared to baseline | Week 10 through study completion |