Efficacy and Safety Study of IFX-1 in Patients With Moderate to Severe Hidradenitis Suppurativa (HS)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether IFX-1 is safe and effective in the treatment of moderate to severe hidradenitis suppurativa.

Detailed Description
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Hidradenitis suppurativa (HS) is a chronic devastating skin disorder affecting areas rich in apocrine glands. HS is diagnosed by its clinical features and its chronicity. It is recognized by the presence of recurrent, painful, deep-seated, rounded nodules usually ending in abscesses and sinus tracts with suppuration and hypertrophic scarring. As complement C5a is involved in the underlying acute inflammatory responses, this study is set up based on the hypothesis that IFX-1 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
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Study to Determine Efficacy and Safety of IFX-1 in Subjects With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa (HS)

Intervention / Treatment
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* Drug: IFX-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ≥ 18 years of age Written informed consent obtained from subject Diagnosis of HS for at least 1 year Moderate or severe HS, as indicated by HS lesions in at least 2 distinct areas, 1 of which must be at least Hurley Stage II or Stage III Inadequate response to at least 3 months of oral antibiotics, or intolerance to antibiotics Total abscess and inflammatory nodule (AN) count of ≥ 3 Exclusion Criteria: Prior treatment with adalimumab or another biologic product during the 24 weeks before Screening Subjects on permitted oral antibiotic treatment for HS (doxycycline or minocycline only) who have not been on a stable dose during the 28 days before Screening Subject received systemic non-biologic therapy for HS with potential therapeutic impact for HS during the 28 days before Screening (other than permitted oral antibiotics) Prior treatment with any of the following medications during the 28 days before Screening: Any other systemic therapy for HS Any iv anti-infective therapy Phototherapy (ultraviolet B or psoralen and ultraviolet A) History of heart disease or malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort 1<br>Placebo | Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 2<br>Minimum Dose IFX-1 (400 mg Q4W) | Drug: IFX-1<br>* Single IV infusions of IFX-1 diluted in sodium chloride.<br>* Other names: Vilobelimab;|
| Experimental: Cohort 3<br>Low dose IFX-1 (800 mg Q4W) | Drug: IFX-1<br>* Single IV infusions of IFX-1 diluted in sodium chloride.<br>* Other names: Vilobelimab;|
| Experimental: Cohort 4<br>Medium Dose IFX-1 (800 mg Q2W) | Drug: IFX-1<br>* Single IV infusions of IFX-1 diluted in sodium chloride.<br>* Other names: Vilobelimab;|
| Experimental: Cohort 5<br>High Dose IFX-1 (1200 mg Q2W) | Drug: IFX-1<br>* Single IV infusions of IFX-1 diluted in sodium chloride.<br>* Other names: Vilobelimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Hidradenitis Suppurativa Clinical Response (HiSCR) Determined at Week 16 | The primary efficacy endpoint of the percentage of patients with HiSCR at Week 16 was analyzed using the multiple comparisons procedure-modelling (MCP-Mod) procedure. The definition for response to treatment based on HiSCR relative to Baseline was: at least 50% reduction in abscesses and inflammatory nodule (AN) count (over all anatomical regions) with no increase in number of abscesses and in number of draining fistulas. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Hidradenitis Suppurativa Clinical Response (HiSCR) Determined at Week 12 | Endpoint of the percentage of patients with HiSCR at Week 12 was analyzed in the same way as the primary endpoint using the MCP-Mod procedure and the same definition of response. | Week 12 | 
| Number of Patients With Flares Relative to Day 1 | The number of patients with flares analyzed in terms of ≥ 25% increase in abscess and inflammatory nodule (AN) count among patients with a minimum increase of 2 in AN count compared to Day 1 was analyzed by descriptive statistics by time point. | From Day 1 until Day 309 | 
| Absolute Change in Modified Sartorius Score (mSS) From Day 1. | The absolute change from Day 1 will be analyzed by descriptive statistics by time point. The mSS is a summation of HS lesions based on a number of factors including anatomical region, number and type of lesions, distance between relevant lesions and lesions clearly separated by normal skin in each region measured as HS clinical parameters. The scale title for mSS is points. The mSS has a minimum value of 0 and no upper limit. The higher the score the more severe is the disease/worse is the outcome. | From Day 1 until Day 309 | 
| Absolute Change in Patient's Global Assessment of Skin Pain From Day 1. | The absolute changes from baseline were analyzed by descriptive statistics by time point. The Numeric Rating Scale (NRS) was used to assess the worst skin pain due to HS. The scale title for the NRS is points. Ratings for this item range from a minimum of 0 points (no skin pain) to a maximum of 10 points (skin pain as bad as you can imagine). The higher the score the more severe the disease/worse is the outcome. | From Day 1 until Day 309 | 
| Percentage of Patients Achieving NRS30 | This is a segmented numeric version of the visual analog scale in which a respondent selects a whole number (0-10) that best reflects the intensity of their pain. The scale title for the NRS is points. The minimum score is 0 points (No skin pain), and the maximum score is 10 points (Skin pain as bad as you can imagine). The higher the score the more severe is the disease/worse is the outcome. The number of patients with at least 30% reduction and at least 1 point reduction from Day 1 in Patients Global Assessment of Skin Pain are displayed. The analysis is based on the worst skin pain the patients reported at the respective visits. | From Day 1 until Day 309 | 
| Percentage of Patients Achieving NRS50. | This is a segmented numeric version of the visual analog scale in which a respondent selects a whole number (0-10) that best reflects the intensity of their pain. The scale title for NRS is points. The minimum score is 0 points (No skin pain), and the maximum score is 10 points (Skin pain as bad as you can imagine). The higher the score the more severe is the disease/worse is the outcome. The number of patients with at least 50% reduction and at least 1 point reduction from Day 1 in Patients Global Assessment of Skin Pain are displayed. The analysis is based on the worst skin pain the patients reported at the respective visits. | From Day 1 until Day 309 | 
| Absolute Change in Dermatology Life Quality Index (DLQI) Score From Day 1. | The changes from Day 1 will be analyzed by descriptive statistics by time point. A score is documented for each of the 10 DLQI items, ranging from 0 to 3 for each item. The scale title for DLQI is points. The total score is the sum of the responses to all 10 DLQI items, ranging from the minimum of 0 points to the maximum of 30 points. A higher score corresponds to worse health related quality of life/outcome. | From Day 1 until Day 309 | 
| Safety Parameters (Adverse Events) Will be Assessed. | The number of patients with any treatment emergent adverse event (adverse events that started after first infusion of IMP) was analyzed by time point. | From Day 1 until Day 309 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hidradenitis suppurativa, monoclonal antibody, complement factor C5a, IFX-1, hidradenitis Suppurativa Clinical Response, Inflammation, skin diseases