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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

InflaRx GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

11 Dec 2023 → 27 May 2025

Decision date (initial)

2023-12-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

InflaRx GmbH

External identifiers

EU CT number

2023-506250-20-00

ClinicalTrials.gov

NCT05964413

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of treatment with vilobelimab compared to placebo in patients with PG

Secondary objectives 1

1. To further evaluate the efficacy of treatment with vilobelimab compared to placebo in patients with PG

Conditions and MedDRA coding

ulcerative pyoderma gangrenosum

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Signed informed consent.
2. 18 years or older at the time of signing the informed consent.
3. 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
4. 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 21

1. Patients with target ulcers exceeding 80 cm2.
2. Patients with target ulcer in transplanted skin
3. 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.
4. 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).
5. Patient with previous exposure to vilobelimab (IFX-1) prior to baseline (i.e., start of treatment with IMP).
6. 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.
7. Patient receives/has received a vaccine within 2 weeks prior to baseline (i.e., start of treatment with IMP).
8. 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).
9. 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.
10. 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.
11. Patients with known congestive heart failure (New York Heart Association criteria Class III or IV).
12. Patients with known progressed liver disease (Child-Pugh class B or C).
13. 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).
14. 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.
15. 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).
16. Major surgery planned during the time of the foreseen study participation.
17. 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.
18. Known or suspected drug and/or alcohol abuse.
19. 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.
20. 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.
21. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients achieving complete closure of the target ulcer up to and including EOT visit; where complete closure of the target ulcer is assessed by the investigator as complete re-epithelization (defined as wound covered by epithelial skin layer or scar) without drainage or dressing requirements confirmed at two consecutive study visits 2 weeks apart.

Secondary endpoints 13

1. 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 confirmed at two consecutive study visits 2 weeks apart.
2. Proportion of patients achieving a pain reduction related to the target ulcer of at least 3 points compared to baseline or reaching 0, at any time between Week 10 and EOT visit inclusively (measured by the 0-10 numeric rating scale (NRS)).
3. Proportion of patients achieving a target ulcer volume reduction of 50% or more compared to baseline, at End of Treatment visit, assessed by the investigator and supported by standardized photographic documentation
4. Proportion of patients achieving a pain reduction related to the target ulcer of at least 2 points compared to baseline or reaching 0, at any time between Week 10 and EOT visit inclusively (measured by the 0-10 NRS).
5. Maximum absolute decrease in target ulcer pain from baseline at any time up to and including EOT visit (assessed by patients on the 0-10 NRS)
6. Absolute change in target ulcer pain from baseline at Week 10, 18, and 26 (assessed by patients on the 0-10 NRS)
7. Maximum reduction of the target ulcer volume by EOT visit compared to baseline.
8. Time to first detected complete closure of the target ulcer; where complete closure of target ulcer is assessed by the investigator as complete re-epithelization (defined as wound covered by epithelial skin layer or scar) without drainage or dressing requirements.
9. Proportion of patients with Patient-Level Stopping Criteria (PLSC) or rescue therapy
10. Time to early stop of study medication due to PLSC or due to opting for rescue therapy
11. Clinician’s Global Impression of Change (CGI-C) from baseline at EOT visit based on a 7-point scale
12. Proportion of patients achieving Physician’s Global Assessment (PGA) score ≤ 1 of the target ulcer up to and including EOT visit.
13. Proportion of patients achieving PGA ≤ 3 of the target ulcer up to and including EOT visit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

InflaRx GmbH

Sponsor organisation

InflaRx GmbH

Address

Winzerlaer Strasse 2, Ammerbach Ammerbach

City

Jena

Postcode

07745

Country

Germany

Scientific contact point

Organisation

InflaRx GmbH

Contact name

Head of Regulatory Affairs

Public contact point

Organisation

InflaRx GmbH

Contact name

Head of Regulatory Affairs

Third parties 8

Locations

8 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 152 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications