A Study to Evaluate the Efficacy, Safety and Tolerability of Bermekimab in Patients With Hidradenitis Suppurativa

Study Overview
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Brief Summary
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This study further evaluates the efficacy of bermekimab in treating moderate to severe hidradenitis suppurativa in adults. 1/3 of patients will receive weekly injections of bermekimab, 1/3 will receive alternating every other week injections of bermekimab or placebo, and 1/3 will receive weekly injections of placebo.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Bermekimab in Patients With Moderate to Severe Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa, Acne Inversa, Suppurative Hidradenitis

Intervention / Treatment
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* Drug: bermekimab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided by the participant Male or female, age greater than or equal to (>=) 18 years Naïve to OR failure of prior targeted biologic therapy for Hidradenitis Suppurativa (HS) (including anti-TNF, anti-IL-17, or JAK inhibitor therapy) 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 participants of childbearing potential, willingness to use one method of contraception of high efficacy during the entire study period. This method can be hormonal contraceptives or 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 or surgically sterilized. Exclusion Criteria: Age below 18 years. History of treatment with bermekimab for any reason. Receipt of oral antibiotic treatment for HS within 28 days prior to baseline. Receipt of prescription topical therapies for the treatment of HS within 14 days prior to baseline, and/or systemic non-biologic therapies for HS (immunosuppressants, corticosteroids, retinoids, or hormonal therapies) within 28 days prior to screening. Participant has been treated with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to baseline. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies. Has received a live (attenuated) vaccine over the 28 days prior to screening. Participant received oral concomitant analgesics (including opioids) for HS-related pain within 14 days prior to baseline. If entering the study on concomitant oral analgesics (including opioids) for non-HS-related pain: (a) Participant on opioid analgesics within 14 days prior to baseline visit; (b) Participant not on a stable dose of non-opioid oral analgesics for at least 14 days prior to baseline visit (PRN is not considered a stable dose). Participant requires or is expected to require opioid analgesics for any reason (excluding tramadol). Participant has a draining fistula count of greater than 20 at baseline. Major surgery (requiring general anesthesia or respiratory assistance) within 28 days prior to Day 0 of start of study drug. Hepatic dysfunction defined as any value of transaminases, of γ-glutamyl transpeptidase (γGT) or of total bilirubin > 3x upper normal limit. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution. Stage C Child-Pugh liver cirrhosis. History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to every week bermekimab injections, every other week bermekimab injections, or every week placebo injections.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bermekimab ew<br>2 800 mg bermekimab loading dose subcutaneous injections, followed by weekly 400 mg bermekimab injections | Drug: bermekimab<br>* bermekimab 2 mL (200 mg/mL) pre-filled syringe<br>|
| Experimental: bermekimab eow<br>2 800 mg loading dose subcutaneous injections, followed by alternating weekly 400 mg bermekimab injections with matching placebo injections | Drug: bermekimab<br>* bermekimab 2 mL (200 mg/mL) pre-filled syringe<br>Drug: placebo<br>* placebo 2 mL pre-filled syringe<br>|
| Placebo Comparator: placebo ew<br>2 800 mg placebo loading dose subcutaneous injections, followed by weekly placebo subcutaneous injections | Drug: placebo<br>* placebo 2 mL pre-filled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | HiSCR was defined as at least 50 percent (%) reduction in total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Numeric Rating Scale (NRS) for Pain & Itch at Weeks 12 and 16 | Change from baseline in NRS for pain and itch at Weeks 12 and 16 was reported. Participants were given a take-home diary to complete each night before bed. Participants were asked to report average pain, and worst moment pain as well as average itch and worst moment itch on a 0 to 10 NRS, where 0=no itch or no pain and 10=worst itch or worst pain. Higher score indicated more severity. | Baseline, Week 12, Week 16 | 
| Change Form Baseline in Total Abscess and Inflammatory Nodule (AN) Count at Weeks 12 and 16 | Change form baseline in total AN count at Weeks 12 and 16 was reported. Abscess and inflammatory nodule were counted for the hidradenitis suppurativa (HS) affected anatomical regions. The AN count is the sum of number of abscess and inflammatory nodules across anatomical regions. | Baseline, Week 12, Week 16 | 
| Change From Baseline in Number of Draining Fistulas at Weeks 12 and 16 | Change form baseline in number of draining fistulas at Weeks 12 and 16 was reported. Draining fistula were defined as fistulas that drain serious or purulent fluid, either spontaneously or by gentle palpation. | Baseline, Week 12, Week 16 | 
| Percentage of Participants Who Achieved Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | HiSCR was defined as at least 50% reduction in AN count with no increase in abscess count and no increase in draining fistula count relative to baseline. | Week 16 | 
| Change From Baseline in Modified Hidradenitis Suppurativa Score (mHSS) at Weeks 12 and 16 | Change from baseline in mHSS at Weeks 12 and 16 was reported. The sartorius scale was used to quantify the severity of HS. Points were awarded for 12 body areas (left and right axillae, left and right sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-crural folds, perianal area, perineal area, and other): points were awarded for nodules (2 points for each); abscesses (4 points); fistulas (4 points); scars (1 point); other findings (1 point); and longest distance between 2 lesions (2-6 points, 0 if no lesions); and if lesions were separated by normal skin (yes: 0 points; no: 6 points). The total sartorius score was the sum of the 12 regional scores. Scale scores range from 0 to infinite, with larger scores representing higher severity of HS. | Baseline, Week 12, Week 16 | 
| Percentage of Participants Who Achieved HS-PGA of Clear (0) or Minimal (1) or HS-PGA Score of Mild or Better (<=2) With at Least a 2-grade Improvement Relative to Baseline at Weeks 12 and 16 | HS-PGA was physician assessment of severity of disease based on 6-point scale:Clear (0)=total number of abscesses, inflammatory nodule, non-inflammatory nodule and draining fistulas was 0;Minimal (1)=total number of abscesses,draining fistulas, inflammatory nodule was 0, presence of non-inflammatory nodule;Mild (2)=total number of abscesses, draining fistulas was 0, total number of inflammatory nodule was 1-4, or presence of 1 abscess or draining fistula and absence of any inflammatory nodules;Moderate (3)=total number of abscesses and draining fistulas was 0, total number of inflammatory nodule was at least 5; or presence of 1 abscess or draining fistula and at least 1 inflammatory nodule; or 2-5 abscesses or draining fistulas, fewer than 10 inflammatory nodule;Severe (4)=total number of abscesses or draining fistulas was 2-5, total number of inflammatory nodule was at least 10;Very severe (5)=more than 5 abscesses or draining fistulas.Higher score indicated more severity of disease. | Weeks 12 and 16 | 
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Weeks 12 and 16 | The HADS was an instrument for screening anxiety and depression in non-psychiatric populations; repeated administration also provides information about changes in a participant's emotional state. It comprises 14 items, seven to assess anxiety (HADS-A), namely items 1, 3, 5, 7, 9, 11, and 13; and seven to assess depression (HADS-D), namely items 2, 4, 6, 8, 10, 12, and 14. Each item receives a score from 0 to 3 on a Likert Scale. The total score for each HADS-A and HADS-D scale was obtained by adding the individual scores for each item, with the maximum score 21. The presence or absence of depression and anxiety was defined, for each respective scale, based on the following cutoff values: HADS (anxiety): 0-8 equal to (=) no anxiety; greater than (>) 9 = anxiety; HADS (depression): 0-8 = no depression; >9 = depression. | Baseline, Week 12, Week 16 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Weeks 12 and 16 | DLQI was a simple, compact, and practical questionnaire to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. The DLQI domains include symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The participant respond on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). The DLQI total score was derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best. A lower score (that is, negative change score) indicated improvement in the Quality of Life. | Baseline, Week 12, Week 16 | 
| Change From Baseline in Health Status as Assessed by EuroQol-5 Dimension Instrument-3 Levels (EQ-5D-3L) Visual Analogue Scale (VAS) Scores at Weeks 12 and 16 | The EQ-5D-3L was a standardized 2-part instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D-3L-VAS records the participant's self-rated health on a vertical VAS that allows the participants to indicate their health state that can range from 0 (worst health you can imagine) to 100 (best health you can imagine). Positive change in score indicated improvement. | Baseline, Week 12, Week 16 | 
| Number of Participants With Patient Global Impression of Change (PGI-c) at Week 12 and 16 | The PGI-c was a single-item patient reported outcome (PRO) that assessed change in severity of skin pain due to HS. Participants rated how his/her HS had changed since the beginning of the study using a 7-point scale ranging from 1 to 7 where 1 indicates very much better, 2 indicates Much better', 3 indicates A little better, 4 indicates No change, 5 indicates A little worse, 6 indicates Much worse and 7 indicates Very much worse. | Week 12, Week 16 | 
| Number of Participants With Patient Global Impression of Severity (PGI-s) at Weeks 12 and 16 | The PGI-s was a single-item PRO that assessed change in a participant's impression of their disease severity. The PGI-s item asks the respondent to best describe how his/her HS symptoms are now (that is, check the one number that best describes how your HS symptoms are now) on a 4-point scale scored as: normal (1), mild (2), moderate (3), or severe (4). | Week 12, Week 16 | 
| Change From Baseline in Hidradenitis Suppurativa (HS)-Related Pain Symptom Score in the Past 24 Hours Based on Hidradenitis Suppurativa Symptom Diary (HSSD) Questionnaire at Weeks 12 and 16 | HSSD is a 7-item patient self-reported questionnaire that assesses 5 HS-related symptoms including pain, tenderness, hot skin feeling, odor, and itchiness. The participants were asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience. All 5 symptoms have a recall period of the past 7 days, except for 2 additional questions on pain which evaluate current pain and pain in the past 24 hours with a score range from 0 (no symptom experience) to 10 (worst possible symptom experience). A total symptom score also ranged from 0 (no symptom) to 10 (worst possible symptom), was derived by averaging the 5 individual scale scores that utilize the past 7-day recall period. Change from baseline in HS-related pain symptom score in the past 24 hours based on HSSD was reported. | Baseline, Week 12, Week 16 | 
| Change From Baseline in Hidradenitis Suppurativa Symptom Diary (HSSD) Total Symptom Score at Weeks 12 and 16 | The HSSD was a 7-item patient self-reported questionnaire that assessed 5 HS-related symptoms including pain, tenderness, hot skin feeling, odor, and itchiness. The participants were asked to rate the severity of each symptom on a 0 to 10 numerical rating scale, with 0 indicating no symptom experience and 10 indicating the worst possible symptom experience. All 5 symptoms had a recall period of the past 7 days, except for 2 additional questions on pain which evaluate current pain and pain in the past 24 hours. Each individual symptom scale score, ranging from 0-10, was summarized. A total symptom score, which also ranged from 0-10, was derived by averaging the 5 individual scale scores that utilize the past 7-day recall period. | Baseline, Week 12, Week 16 | 
| Serum Concentration of Bermekimab | Serum concentration of bermekimab was reported. This outcome measure was planned to be analyzed for specified arms only. | Baseline (Week 0), Weeks 1, 2, 3, 4, 5, 8, 12, and 16 | 
| Reduction From Baseline in Serum Interleukin-6 (IL-6) | Reduction from baseline in serum IL-6 was reported. | Baseline, Weeks 8, 12 and 16 |