Exploratory Study of IFX-1 in Patients With Pyoderma Gangrenosum

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether vilobelimab (development name: IFX-1) is safe and effective in the treatment of pyoderma gangrenosum.

Detailed Description
-----------------
Neutrophilic dermatoses are a spectrum of inflammatory disorders characterized by skin lesions resulting from a neutrophil-rich inflammatory infiltrate in the absence of infection. Pyoderma gangrenosum is associated with a neutrophilic leukocytosis, which is likely to be triggered by C5a. This study is set up based on the hypothesis that vilobelimab might be able to block C5a induced pro-inflammatory effects such as neutrophil activation and cytokine generation, potentially contributing to the local skin inflammation and tissue damage.

Official Title
-----------------
Open Label Exploratory Phase IIa Trial to Investigate the Safety and Efficacy of IFX-1 in Treating Patients With Pyoderma Gangrenosum (OPTIMA)

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of an ulcerative form of pyoderma gangrenosum confirmed by the investigator In addition, the subject must fulfill at least 3 of the following 6 criteria at screening: History of Pathergy (ulcer occurring at the sites of trauma) Personal history of inflammatory bowel disease or inflammatory arthritis History of papule, pustule or vesicle that rapidly ulcerated Clinical examination (or photographic evidence) of Peripheral erythema, undermining border, and tenderness at site of ulceration Multiple ulcerations (at least 1 occurring on the lower leg) Cribriform or wrinkled paper scar(s) at sites of healed ulcers Subject has a minimum of 1 evaluable ulcer (≥2 cm2) on the lower extremity at screening Exclusion Criteria: Pyoderma gangrenosum target ulcer for more than 3 years before screening Surgical wound debridement within the previous 2 weeks before screening Use of intravenous antibacterials, antivirals, anti-fungals, or anti-parasitic agents within 30 days before screening Any drug treatment for pyoderma gangrenosum including corticosteroids (>10 mg), intralesional steroids, cyclosporine A, biologicals and immunosuppressives (with the exception of antibiotics for wound superinfection) used within a time of 5 half-lives of the drug before screening

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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: IV infusions of vilobelimab diluted in sodium chloride
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vilobelimab 800 mg Q2W<br>Dose finding with a total of 15 doses of vilobelimab. Vilobelimab: IV infusions of vilobelimab diluted in sodium chloride. All patients received vilobelimab 800 mg three times during the first week (Days 1, 4, and 8). Starting at Day 15: Group 1 (N=6) continued to receive vilobelimab 800 mg every 2 weeks (Q2W), with option to increase dose from Day 57 to 1600 mg every Q2W. | Drug: vilobelimab<br>* IV infusions of vilobelimab diluted in sodium chloride.<br>* Other names: CaCP29;|
| Experimental: vilobelimab 1600 mg Q2W<br>Dose finding with a total of 15 doses of vilobelimab. Vilobelimab: IV infusions of vilobelimab diluted in sodium chloride. All patients received vilobelimab 800 mg three times during the first week (Days 1, 4, and 8). Starting at Day 15: Group 2 (N=6) received vilobelimab 1600 mg every 2 weeks (Q2W), with option to increase dose from Day 57 to 2400 mg every Q2W. | Drug: vilobelimab<br>* IV infusions of vilobelimab diluted in sodium chloride.<br>* Other names: CaCP29;|
| Experimental: vilobelimab 2400 mg Q2W<br>Dose finding with a total of 15 doses of vilobelimab. Vilobelimab: IV infusions of vilobelimab diluted in sodium chloride. All patients received vilobelimab 800 mg three times during the first week (Days 1, 4, and 8). Starting at Day 15: Group 3 (N=7) received vilobelimab 2400 mg every Q2W. | Drug: vilobelimab<br>* IV infusions of vilobelimab diluted in sodium chloride.<br>* Other names: CaCP29;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events (TEAEs), Related TEAEs, Serious TEAEs, and Adverse Events of Special Interest (AESIs) | Number of patients with treatment-emergent adverse events (TEAEs), related TEAEs, serious TEAEs, and adverse events of special interest (AESIs) TEAEs are defined as adverse events that start at or after the first administration of study drug. Related TEAEs are defined as all TEAEs considered by the investigator to have at least a 'possible' relationship with the study drug. AESIs are defined as infusion-related reactions, including acute and delayed hypersensitivity and anaphylactic reactions during or after infusion; Meningitis; Meningococcal septicaemia; Invasive infection. As adverse events will be reported in details in the safety section, no separate reporting on System Organ Class (SOC) or Preferred Term (PT) level etc. is done here. | From treatment start until end of study (including observational visits), an average of 249 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Physician's Global Assessment (PGA) Score ≤3 (Investigator Assessment) | Efficacy endpoint: Proportion of patients with a clinical response, defined as Physician's Global Assessment (PGA) score ≤3 of target ulcer at Visit V4, V6, V10 and V16 (End of Treatment [EOT]) (SAF). PGA values: 0 = Completely clear, 1 = Almost clear, 2 =Marked improvement, 3 = Moderate improvement, 4 = Slight improvement, 5 = No change from baseline, 6 = Worse | From treatment start until V16 (Day 189) | 
| Time to Complete Closure of Pyoderma Gangrenosum Target Ulcer (Investigator Assessment) [Days] | Efficacy endpoint: Kaplan-Meier analysis of time to first clinical remission (complete closure of target ulcer) defined as PGA score of ≤ 1, PGA values: 0 = Completely clear, 1 = Almost clear, 2 =Marked improvement, 3 = Moderate improvement, 4 = Slight improvement, 5 = No change from baseline, 6 = Worse | From treatment start until end of study (including observational visits), an average of 249 days | 
| Percentage Change in Wound Healing (Wound Area) by Photographic Assessment | Efficacy endpoint: Percentage change in wound area [percent change] of target ulcer by photographic assessment between Visits V1 and V4, between Visits V1 and V6, between Visits V1 and V16, between Visits V6 and V10, between Visits V10 and V16. | From treatment start until V16 (Day 189) | 
| Percentage Change in Wound Healing (Wound Volume) by Photographic Assessment | Efficacy endpoint: Percentage change in wound volume [percent change] of target ulcer by photographic assessment between Visits V1 and V4, between Visits V1 and V6, between Visits V1 and V16, between Visits V6 and V10, between Visits V10 and V16. | From treatment start until V16 (Day 189) | 
| Rate of Change Per Day in Area of Target Ulcer by Photographic Assessment From V1 to V16 | Efficacy endpoint: Rate of change per day in area of target ulcer [mm²/day] between Visits V1 and V16 (photographic assessment) | From treatment start until V16 (Day 189) | 
| Number of Patients With ≥ 50% Decrease in Area of Target Ulcer by Photographic Assessment at V16 | Efficacy endpoint: Number of patients with a decrease in area of target ulcer of ≥ 50% by photographic assessment at Visit V16 (EOT) compared to Baseline | From treatment start until V16 (Day 189) | 
| Number of Patients With 100% Decrease in Area of Target Ulcer at V16 | Efficacy endpoint: Number of patients with a decrease in area of target ulcer of 100% at Visit V16 (EOT) compared to Baseline (remission) (photographic assessment) | From treatment start until V16 (Day 189) | 
| Degree of Erythema of the Target Ulcer at V4, V6, V10 and V16 | Efficacy endpoint: Degree of erythema of the target ulcer at Visit V4, V6, V10 and V16 (EOT) (investigator assessment) | From treatment start until V16 (Day 189) | 
| Border Elevation of the Target Ulcer at Visits V4, V6, V10 and V16 | Efficacy endpoint: Border elevation of the target ulcer at visits V4, V6, V10 and V16 (EOT) (investigator assessment) | From treatment start until V16 (Day 189) | 
| Percentage Change in Pain by Numeric Rating Scale (NRS) at Visits V4, V6, V10 and V16 | Efficacy endpoint: Percentage change from Baseline in pain assessed by Numeric Rating Scale (NRS) [percent change] at visits V4, V6, V10 and V16 (EOT) Mean (SD) The NRS is an 11-point scale (from 0 represent no pain to 10 representing the worst pain the subject can imagine). | From treatment start until V16 (Day 189) | 
| Percentage Change in Life Quality by DLQI at Visits V4, V6, V10, and V16 | Efficacy endpoint: Percentage change from Baseline in Dermatology Life Quality Index (DLQI) [percent change] at visits V4, V6, V10, and V16 (EOT) The DLQI comprises 10 questions with single scores 0 (No effect on patient's life) to 3 (large effect on patient's life). The DLQI total score is calculated by summing up the score of each question resulting in a minimum of 0 (best) and a maximum of 30 (worst). | From treatment start until V16 (Day 189) |