A Study of Bermekimab in Patients With Hidradenitis Suppurativa

Study Overview
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Brief Summary
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Phase 2 study of bermekimab in patients with moderate to severe Hidradenitis Suppurativa.

Detailed Description
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Phase 2, open label study of bermekimab in patients with moderate to severe Hidradenitis Suppurativa. The study is multicenter and will consist of two patient groups, each of which will receive a total of 13 X 400mg weekly subcutaneous injections of bermekimab: Group A (n=10) patients who have failed anti-TNF therapy, and Group B (n=10) patients who have had no prior treatment with biological agents that block TNF. Patients will be followed for 13 weeks to allow for assessment of safety and preliminary efficacy. Additionally, patients who had received the 200 mg weekly subcutaneous injections of bermekimab under the previous version of this protocol are eligible to begin receiving the 400 mg dose starting with his/her next scheduled visit, and for the remainder of his/her treatment plan. XBiotech owned bermekimab and sponsored and completed study prior to Dec 30, 2019.

Official Title
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A Phase II, Open Label Study of Bermekimab in Patients With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: Bermekimab Monoclonal Antibody 400 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided by the patient. Male or female, age 18 years or greater. For group A, patients must have received and failed anti-TNF therapy. For Group B, patients must not have received any prior treatment with any anti-TNF therapy. Patients who have received 200 mg dose of bermekimab in this study (previous version(s)) are eligible to begin receiving 400 mg dose starting with the patient's next scheduled visit for the remainder of his/her treatment plan. Diagnosis of HS for at least 1 year prior to screening. HS affecting at least two distinct anatomic areas, one of which is Hurley II or III stage. A total body count of abscesses and inflammatory nodules (AN) of at least 3 Full understanding of the procedures of the study protocol and willingness to comply with them. In case of female patients of childbearing potential, willingness to use one method of contraception of high efficacy during the entire study period. This method can be intake of hormonal contraceptives or the use of one of the following: condoms, diaphragm or an intrauterine device. Women of non-childbearing potential include those considered to have a medical history that indicates that pregnancy is not a reasonable risk, including post-menopausal women and those with a history of hysterectomy. Exclusion Criteria: Age below 18 years. Receipt of oral antibiotic treatment for HS within 28 days prior to screening. Receipt of prescription topical therapies for the treatment of HS within 14 days prior to screening, and/or systemic therapies for HS (immunosuppressants, corticosteroids, retinoids, or hormonal therapies) within 28 days prior to screening. History of treatment with bermekimab for any reason, EXCEPT patients previously treated with 200 mg bermekimab dose in the previous version(s) of this study. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies. Has received a live (attenuated) vaccine over the 4 weeks prior to screening. New intake of opioid analgesics starting within 14 days prior to screening. Major surgery (requiring general anesthesia or respiratory assistance) within 28 days prior to Visit 1, Day 0 of start of study drug. Hepatic dysfunction defined as any value of transaminases or of γ-glutamyl transpeptidase (γGT), or of total bilirubin > 3 x upper normal limit Stage C Child-Pugh liver cirrhosis. Chronic infection by the human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Neutropenia defined as <1,000 neutrophils/mm3. Pregnancy or lactation.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 400mg cohort, no prior treatment with anti-TNF agent(s)<br>N=10 patients that have had no prior treatment with biological agents that block TNF will receive a total of 13 X 400mg subcutaneous injections of bermekimab. Dosing will occur weekly for 12 weeks, inclusive of visit 1 and visit 13. | Drug: Bermekimab Monoclonal Antibody 400 mg<br>* subcutaneous injection<br>* Other names: MABp1;|
| Experimental: 400 mg cohort, prior treatment with anti-TNF agent(s)<br>N=10 patients that have failed anti-TNF therapy will receive a total of 13 X 400mg subcutaneous injections of bermekimab. Dosing will occur weekly for 12 weeks, inclusive of visit 1 and visit 13. | Drug: Bermekimab Monoclonal Antibody 400 mg<br>* subcutaneous injection<br>* Other names: MABp1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event is defined as any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical or biological agent under study. | Up to Visit 14 (up to Day 93) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | Percentage of participants achieving HiSCR at Week 12 was reported. For this score participants were defined as achievers or non-achievers. The positive HiSCR score was defined as a greater than or equal to (>=) 50% reduction in inflammatory lesion AN count (sum of abscesses and inflammatory nodules), and no increase in abscesses or draining fistulas in hidradenitis suppurativa compared with the lesions counted on visit 1 (baseline). | Week 12 | 
| Plasma Concentration of Bermekimab | An enzyme-linked immunosorbent assay (ELISA) was developed to specifically measure bermekimab levels in human plasma. The blood samples were collected at each pharmacokinetic (PK) collection time point for PK analysis. | Predose at Days 14 (Visit 3), 28 (Visit 5), 56 (Visit 9), 84 (Visit 13) | 
| Change From Baseline to Week 12 in Visual Analog Scale (VAS) Score for Disease | Change from baseline in VAS score for disease was reported. The VAS is a validated, subjective measure for participants disease impression. Disease impression scores were recorded using a similar scale, with 0 representing not at all severe and 10 representing extremely severe. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in VAS Score for Pain | Change from baseline in VAS score for pain was reported. The VAS is a validated, subjective measure for acute and chronic pain. Pain scores were recorded by marking a number on a scale from 0 to 10, 0 representing no pain and 10 representing extremely painful. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Dermatology Life Quality Index (DLQI) Score | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of disease symptoms and treatment on Quality of life (QOL). The format is a simple response (0 to 3 where 0 is not at all and 3 is very much) to 10 questions, which assess QOL over the past week, with an overall scoring system of 0 to 30; a high score is indicative of a poor QOL. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Physician's Global Assessment (PGA) Score | PGA is a physician's assessment of the severity of disease based on a 6-point scale (Clear [0], minimal [1], mild [2], moderate [3], severe [4], more severe [5]) ranging from 0-5. Higher score indicated more severity of disease. | Baseline and Week 12 | 
| Change From Baseline in Disease Activity Score (DAS) at Week 12 | The DAS is the sum of scores of all affected areas of each participant. Each area was evaluated by the following formula: (the sum of the two largest diameters in each affected area in millimeter [mm]) * (Total number of lesions in the anatomic area multiplied by the degree of inflammation of each lesion on a scale of 0 to 3). A minimum score of 0 and there is no maximum score range. Higher scores indicate more disease activity. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Modified Sartorius Score (mSS) | mSS is used to quantify severity of HS. Points are awarded for 12 body areas (left-right axillae, left - right sub/inframammary areas, intermammary area, left - right buttocks, left-right inguinocrural folds, perianal area, perineal area and other): points were awarded for nodules (2 points each);abscesses (4points);fistulas (4points);scars (1point); other findings (1 point); and longest distance between two lesions (no active lesion or only 1 lesion equal to [=]0 points, less than [<]5cm=2points, 5-10cm=4points, greater than [>]10cm 6points) and if lesions are separated by normal skin (yes-0 points; no-6points). Total mSS is sum of the 12 regional scores. Change from baseline in mSS was not reported as the electronic data capture (EDC) system erroneously requested data for this endpoint to be input in centimeters versus millimeters and conversion was not possible because it was given in ranges. Therefore, there was not enough valid data to sufficiently perform this endpoint analysis. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Inflammatory Lesion (Abscesses and Inflammatory Nodules) Count | Change from baseline to Week 12 in inflammatory lesion (abscesses and inflammatory nodules) count was reported. The sum of abscesses and inflammatory nodules was measured for each participant to assess change in inflammatory lesion counts. | Baseline and Week 12 | 
| Change From Baseline to Week 12 in Hospital Anxiety Depression Scale (HADS) | The HADS is an instrument for screening anxiety and depression in non-psychiatric populations; repeated administration also provides information about changes to a patient's emotional state. The HADS consisted of 14 items, 7 each for anxiety and depression symptoms; possible scores range from 0 to 21 for each subscale. The following cut-off scores were recommended for both subscales: 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hidradenitis Suppurativa