Efficacy and Safety Evaluation of Vilobelimab in Ulcerative Pyoderma Gangrenosum: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial
- Trial ID
- 2023-506250-20-00
- Protocol
- IFX-1-P3.4
- Sponsor
- InflaRx GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of treatment with vilobelimab compared to placebo in patients with ulcerative pyoderma gangrenosum. This is clinically relevant as it aims to determine the potential therapeutic benefits of vilobelimab, which could lead to improved management of this debilitating condition.
Secondary objectives include further evaluation of the efficacy of vilobelimab compared to placebo in the same patient population. This additional assessment is crucial for understanding the full therapeutic potential and impact of vilobelimab on patient outcomes.
Participants
The clinical trial involves a total of **48 participants** diagnosed with **ulcerative pyoderma gangrenosum**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on a confirmed clinical diagnosis of ulcerative pyoderma gangrenosum, supported by a PARACELSUS score of 10 points or more, and the presence of at least one evaluable ulcer meeting specific criteria. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity were highlighted. The selection process required signed informed consent from all participants, ensuring they were adequately informed about the study. The trial aims to evaluate the efficacy of vilobelimab compared to placebo in this patient group.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled, multicenter, adaptive phase III study** to evaluate the efficacy and safety of **vilobelimab** in the treatment of **ulcerative pyoderma gangrenosum**. The trial aims to compare the effects of vilobelimab with a placebo, with the primary objective being the complete closure of the target ulcer, assessed by the investigator as complete re-epithelization without drainage or dressing requirements. The trial is expected to run until January 6, 2026, with recruitment starting on November 3, 2023.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical diagnosis, and ulcer characteristics. The trial will include follow-up visits at regular intervals to monitor progress and assess endpoints, such as disease remission and pain reduction. The end-of-study visit will evaluate the overall outcomes and any adverse effects experienced by participants. The expected length of participant involvement is up to 26 weeks, depending on individual response and adherence to the protocol.
Participants may be withdrawn from the study early if they meet specific stopping criteria, require rescue therapy, or experience significant adverse events. The trial will utilize oral administration of glucocorticoids such as **prednisone**, **betamethasone**, and **methylprednisolone**, among others, alongside the intravenous administration of vilobelimab. The study will ensure that all procedures adhere to ethical standards and regulatory requirements, maintaining the integrity and scientific validity of the trial outcomes.
Treatment
The clinical trial involves the administration of several **experimental medications** and a placebo. **Prednisone** is administered in the form of a tablet, with a maximum daily dose of 5 mg. The route of administration is oral, and the treatment period extends up to 57 days. Prednisone is classified as a glucocorticoid.
**Betamethasone** is provided as a coated tablet, with a maximum daily dose of 0.75 mg. It is administered orally over a treatment period of 56 days. Betamethasone is also categorized as a glucocorticoid.
**Fludrocortisone** is administered in tablet form, with a maximum daily dose of 0.2 mg. The oral administration is maintained for a period of 56 days. Fludrocortisone is classified as a mineralocorticoid.
**Prednisolone** is available as a tablet, with a maximum daily dose of 20 mg. The route of administration is oral, and the treatment duration is 56 days. Prednisolone is categorized as a corticosteroid.
**Cortisone acetate** is administered in tablet form, with a maximum daily dose of 25 mg. The oral administration is conducted over a 56-day period. Cortisone acetate is classified as a glucocorticoid.
**Hydrocortisone** is provided in tablet form, with a maximum daily dose of 20 mg. It is administered orally for a period of 56 days. Hydrocortisone is classified as a glucocorticoid.
**Triamcinolone** is administered as a tablet, with a maximum daily dose of 4 mg. The route of administration is oral, and the treatment period is 56 days. Triamcinolone is categorized as a glucocorticoid.
**Dexamethasone** is available in tablet form, with a maximum daily dose of 0.75 mg. The oral administration is maintained for 56 days. Dexamethasone is classified as a glucocorticoid.
**Methylprednisolone** is administered in tablet form, with a maximum daily dose of 4 mg. The route of administration is oral, and the treatment duration is 56 days. Methylprednisolone is categorized as a glucocorticoid.
**Vilobelimab**, marketed as Gohibic, is administered as a solution for infusion. The maximum daily dose is 2400 mg, and the route of administration is intravenous. The treatment period extends up to 26 days. Vilobelimab is an immunoglobulin, specifically an anti-human complement C5a monoclonal antibody (human/mouse chimeric IgG4).
The **placebo** used in the trial is formulated as PBS (150 mM sodium chloride, 10 mM sodium phosphate, pH 7.0) with 0.05% polysorbate 80. It is diluted in sterile 0.9% sodium chloride to the required concentration and volume. The placebo is administered intravenously.
Efficacy
The efficacy of the treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients achieving complete closure of the target ulcer, defined as complete re-epithelization without drainage or dressing requirements, confirmed at two consecutive study visits two weeks apart. This assessment will be conducted by the investigator.
Secondary endpoints include several measures: the proportion of patients achieving disease remission, pain reduction related to the target ulcer, and a reduction in target ulcer volume. Disease remission is similarly defined as complete re-epithelization of all ulcers without drainage or dressing needs, confirmed at two consecutive visits. Pain reduction will be measured using a 0-10 numeric rating scale (NRS), with specific thresholds for reduction at different time points. The reduction in ulcer volume will be assessed by the investigator and supported by standardized photographic documentation.
Additional secondary endpoints include the maximum absolute decrease in target ulcer pain, absolute change in pain at specified weeks, maximum reduction of ulcer volume by the end of treatment, and time to first detected complete closure of the target ulcer. Other measures include the proportion of patients meeting Patient-Level Stopping Criteria or requiring rescue therapy, time to early stop of study medication, and assessments using the Clinician’s Global Impression of Change (CGI-C) and Physician’s Global Assessment (PGA) scores.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent.
- 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 of 10 points or more
- Minimum of 1 evaluable PG ulcer (other than peristomal) which qualifies as the target ulcer by meeting the following criteria • area of ≥ 5 cm2 at screening and baseline • circulated by intact skin • evaluable by at least 2-dimensional measurement
Exclusion Criteria
- Patients with target ulcers exceeding 80 cm2.
- Patients with target ulcer in transplanted skin
- Significant improvement and visual ulcer decrease of the target ulcer between screening and baseline (i.e., start of treatment with IMP) as judged by the investigator supported by standardized photography.
- 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 with known severe or life-threatening hypersensitivity reaction to any other therapeutic antibodies according to Common Terminology Criteria for Adverse Events (CTCAE) such as breathing difficulty, dizziness, hypotension, cyanosis, and loss of consciousness.
- 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 (e.g., erysipelas, herpes zoster, syphilis, pneumonia, tuberculosis, pneumocystis, aspergillosis, cytomegalovirus, and atypical mycobacteria) within 2 weeks prior to baseline (i.e., start of treatment with IMP).
- Patient has a known history of tuberculosis, human immunodeficiency virus (HIV) infection or a known history of or a suspected current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- Patient has a history of malignancies during the past 5 years other than successfully treated basal cell carcinoma, locally non-advanced, non-metastatic cutaneous squamous cell carcinoma, or carcinoma of the cervix in situ.
- Patients with known congestive heart failure (New York Heart Association criteria Class III or IV).
- Patients with known progressed liver disease (Child-Pugh class B or C).
- Patients received any systemic medical treatment for PG within 4 weeks prior to baseline (i.e., start of treatment with IMP) (e.g., cyclosporine, mycophenolate mofetil, methotrexate [MTX], azathioprine [AZA], intravenous immunoglobulin [IVIg], systemic corticosteroids other than as detailed under exclusion criterion 14) and 15), or receives/received topical or intralesional treatment within 2 weeks prior to baseline (i.e., start of treatment with IMP).
- 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; e.g.: psoriasis, inflammatory bowel disease (IBD)) 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). Note: If a patient is on oral corticosteroid therapy, the dose must be tapered to 10 mg/day prednisone (or its equivalent) and the dose must be stable for at least 4 weeks prior to baseline, without visual decrease in the target ulcer size between screening and baseline according to investigators’ judgment. Patients with no prior corticosteroid therapy are allowed to receive up to 10 mg/day prednisone (or its equivalent) prior to baseline (i.e., start of treatment with IMP).
- Major surgery planned during the time of the foreseen study participation.
- The patient has participated in an interventional clinical trial and is known to have received active treatment during the 3 months before screening or plans to participate in another clinical trial.
- Known or suspected drug and/or alcohol abuse.
- Women of childbearing potential (WOCBP) who have a positive serum pregnancy test result within 7 days before treatment or are breast feeding. Note: Postmenopausal women must be amenorrheic for ≥ 12 months to be considered not WOCBP.
- WOCBP and males of any age unwilling to practice an effective method of contraception during the treatment period and for at least 30 days after the last dose of IMP.
- Any existing concomitant disease which, in the investigator’s opinion, is likely to compromise the patient’s ability to participate in the study or would interfere with the efficacy assessment of the trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 03 Nov 2023 | 5 |
 France | Not Recruiting | 03 Nov 2023 | 10 |
 Germany | Not Recruiting | 03 Nov 2023 | 21 |
 Hungary | Not Recruiting | 03 Nov 2023 | 9 |
 Italy | Not Recruiting | 03 Nov 2023 | 16 |
 The Netherlands | Not Recruiting | 03 Nov 2023 | — |
 Poland | Not Recruiting | 03 Nov 2023 | 19 |
 Spain | Not Recruiting | 03 Nov 2023 | 13 |
| Netherlands | — | — | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PREDNISOLONE | Other | — | ORAL | 20 | 56 | SUB10018MIG |
CORTISONE ACETATE | Other | — | ORAL | 25 | 56 | SUB01467MIG |
FLUDROCORTISONE | Other | — | ORAL | 0.2 | 56 | SUB07684MIG |
Gohibic | Test | SOLUTION FOR INFUSION | INTRAVENOUS | 2400 | 26 | PRD6539674 |
TRIAMCINOLONE | Other | — | ORAL | 4 | 56 | SUB11251MIG |
PREDNISONE | Other | — | ORAL | 5 | 57 | SUB10020MIG |
DEXAMETHASONE | Other | — | ORAL | 0.75 | 56 | SUB07017MIG |
HYDROCORTISONE | Other | — | ORAL | 20 | 56 | SUB08065MIG |
METHYLPREDNISOLONE | Other | — | ORAL | 4 | 56 | SUB08872MIG |
IFX-1 placebo is formulated as PBS (150 mM sodium chloride, 10 mM sodium phosphate, pH 7.0)
with 0.05% polysorbate 80.
IFX-1 placebo is diluted in sterile 0.9% sodium chloride to the required concentration and volume.
This diluent is a commercial product not accompanying IFX-1 placebo. | Placebo | N/A | INTRAVENOUS USE | — | — | N/A |