A Study to Evaluate the Efficacy, Safety and Tolerability of Bermekimab in Patients With Hidradenitis Suppurativa
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: bermekimab ew 2 800 mg bermekimab loading dose subcutaneous injections, followed by weekly 400 mg bermekimab injections |
Drug: bermekimab
bermekimab 2 mL (200 mg/mL) pre-filled syringe
|
| Experimental: bermekimab eow 2 800 mg loading dose subcutaneous injections, followed by alternating weekly 400 mg bermekimab injections with matching placebo injections |
Drug: bermekimab
bermekimab 2 mL (200 mg/mL) pre-filled syringe
Drug: placebo
placebo 2 mL pre-filled syringe
|
| Placebo Comparator: placebo ew 2 800 mg placebo loading dose subcutaneous injections, followed by weekly placebo subcutaneous injections |
Drug: placebo
placebo 2 mL pre-filled syringe
|
Outcome Measures
Primary Outcome Measures
- Percentage of subjects achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 [Week 12]
HiSCR is 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
Secondary Outcome Measures
- Change from Baseline to Week 16 in Numeric Rating Scale for Pain & Itch (NRS Pain & Itch) [Baseline (Week 0) and Week 16]
Patients will be given a diary to complete each night before bed. Patients will be asked to report "average pain", and "worst moment pain" as well as "average itch" and "worst moment itch" on a 0-10 numeric rating scale. Patient diaries will be collected weekly.
- Change from Baseline to Week 12 in Numeric Rating Scale for Pain & Itch (NRS Pain & Itch) [Baseline (Week 0) and Week 12]
Patients will be given a diary to complete each night before bed. Patients will be asked to report "average pain", and "worst moment pain" as well as "average itch" and "worst moment itch" on a 0-10 numeric rating scale. Patient diaries will be collected weekly.
- Change from Baseline to Week 8 in Numeric Rating Scale for Pain & Itch (NRS Pain & Itch) [Baseline (Week 0) and Week 8]
Patients will be given a diary to complete each night before bed. Patients will be asked to report "average pain", and "worst moment pain" as well as "average itch" and "worst moment itch" on a 0-10 numeric rating scale. Patient diaries will be collected weekly.
- Percentage of subjects achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at week 16 [Week 16]
HiSCR is 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
- Change from Baseline to Week 16 in Hidradenitis Suppurativa Symptom Diary (HSSD) HS related Pain Symptom Score in the past 24 hours [Baseline (Week 0) and Week 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 are asked to rate the severity of each symptom on a 0 to 10 numerical rating scale over the past week, 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. Change from baseline in HS-related pain symptom score (ranging from 0 to 10) will be determined. Patient diaries will be collected weekly.
- Change from Baseline to Week 12 in Hidradenitis Suppurativa Symptom Diary (HSSD) HS related Pain Symptom Score in the past 24 hours [Baseline (Week 0) and Week 12]
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 are asked to rate the severity of each symptom on a 0 to 10 numerical rating scale over the past week, 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. Change from baseline in HS-related pain symptom score (ranging from 0 to 10) will be determined. Patient diaries will be collected weekly.
- Change from Baseline to Week 16 in Modified Hidradenitis Suppurativa Score (mHSS) [Baseline (Week 0) and Week 16]
The mHSS, also referred to as the Modified Sartorius Score, is used to quantify the severity of HS. Points are 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 two lesions (2-6 points, 0 if no lesions); and if lesions are separated by normal skin (yes-0 points; no-6 points). The total mHSS is the sum of the 12 regional scores
- Change from Baseline to Week 12 in Modified Hidradenitis Suppurativa Score (mHSS) [Baseline (Week 0) and Week 12]
The mHSS, also referred to as the Modified Sartorius Score, is used to quantify the severity of HS. Points are 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 two lesions (2-6 points, 0 if no lesions); and if lesions are separated by normal skin (yes-0 points; no-6 points). The total mHSS is the sum of the 12 regional scores
- Change from Baseline to Week 16 in Hurley Stage [Baseline (Week 0) and Week 16]
The Hurley stage is used to qualify the severity of HS. Affected anatomic regions are individually scored. Hurley Stage I is defined as localized formation of single or multiple abscesses without sinus tracts and scarring. Hurley Stage II is defined as recurrent abscesses with sinus tract formation and scarring; single or multiple lesions. Hurley Stage III is defined as diffuse involvement with interconnected tracts and abscesses.
- Change from Baseline to Week 12 in Hurley Stage [Baseline (Week 0) and Week 12]
The Hurley stage is used to qualify the severity of HS. Affected anatomic regions are individually scored. Hurley Stage I is defined as localized formation of single or multiple abscesses without sinus tracts and scarring. Hurley Stage II is defined as recurrent abscesses with sinus tract formation and scarring; single or multiple lesions. Hurley Stage III is defined as diffuse involvement with interconnected tracts and abscesses.
- Change from Baseline to Week 16 in Hidradenitis Suppurativa Physician's Global Assessment (HS-PGA) [Baseline (Week 0) and Week 16]
The HS-PGA documents the physician's assessment of the participant's HS at a given timepoint. HS-PGA scoring is scores patient disease severity as one of the following: a) clear - 0 abscesses, 0 draining fistulas, 0 inflammatory nodules, and 0 noninflammatory nodules b) minimal - 0 abscesses, 0 draining fistulas, 0 inflammatory nodules, and presence of noninflammatory nodules c) mild - 0 abscesses, 0 draining fistulas, and 1-4 inflammatory nodules or 1 abscess or draining fistula and 0 inflammatory nodules d) moderate - 0 abscesses, 0 draining fistulas, and ≥ 5 inflammatory nodules or 1 abscess or draining fistula and ≥ 1 inflammatory nodule or 2-5 abscesses or draining fistulas and ≥ 10 inflammatory nodules e) severe - 2-5 abscesses or draining fistulas and 10 inflammatory nodules f)very severe - when > 5 abscesses or draining fistulas
- Change from Baseline to Week 12 in Hidradenitis Suppurativa Physician's Global Assessment (HS-PGA) [Baseline (Week 0) and Week 12]
The HS-PGA documents the physician's assessment of the participant's HS at a given timepoint. HS-PGA scoring is scores patient disease severity as one of the following: a) clear - 0 abscesses, 0 draining fistulas, 0 inflammatory nodules, and 0 noninflammatory nodules b) minimal - 0 abscesses, 0 draining fistulas, 0 inflammatory nodules, and presence of noninflammatory nodules c) mild - 0 abscesses, 0 draining fistulas, and 1-4 inflammatory nodules or 1 abscess or draining fistula and 0 inflammatory nodules d) moderate - 0 abscesses, 0 draining fistulas, and ≥ 5 inflammatory nodules or 1 abscess or draining fistula and ≥ 1 inflammatory nodule or 2-5 abscesses or draining fistulas and ≥ 10 inflammatory nodules e) severe - 2-5 abscesses or draining fistulas and 10 inflammatory nodules f)very severe - when > 5 abscesses or draining fistulas
- Change from Baseline to Week 16 in Hospital Anxiety and Depression Scale (HADS) [Baseline (Week 0) and Week 16]
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 consists 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 are 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.
- Change from Baseline to Week 12 in Hospital Anxiety and Depression Scale (HADS) [Baseline (Week 0) and Week 12]
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 consists 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 are 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.
- Change from Baseline to Week 16 in Dermatology Life Quality Index (DLQI) [Baseline (Week 0) and Week 16]
The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on 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
- Change from Baseline to Week 12 in Dermatology Life Quality Index (DLQI) [Baseline (Week 0) and Week 12]
The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on 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
- Change from Baseline to Week 16 in Patient Global Assessment of Change (PGI-c) [Baseline (Week 0) and Week 16]
The PGI-c is a single item patient reported outcome that assesses change in severity of skin pain due to HS. Participants will rate how his/her HS has changed since the beginning of the study using a 7-point scale ranging from 1 which indicates "very much better" to 7 which indicates "very much worse" with a neutral center point 4 whichindicates ("no change")
- Change from Baseline to Week 12 in Patient Global Assessment of Change (PGI-c) [Baseline (Week 0) and Week 12]
The PGI-c is a single item patient reported outcome that assesses change in severity of skin pain due to HS. Participants will rate how his/her HS has changed since the beginning of the study using a 7-point scale ranging from 1 which indicates "very much better" to 7 which indicates "very much worse" with a neutral center point 4 which indicates ("no change")
- Change from Baseline to Week 16 in Patient Global Assessment of Severity (PGI-s) [Baseline (Week 0) to Week 16]
The PGI-s is a single item patient reported outcome that assesses change in a patient's impression of their disease severity. The PGI-s item asks the respondent to best describe how his/her HS symptoms are now ("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)".
- Change from Baseline to Week 12 in Patient Global Assessment of Severity (PGI-s) [Baseline (Week 0) to Week 12]
The PGI-s is a single item patient reported outcome that assesses change in a patient's impression of their disease severity. The PGI-s item asks the respondent to best describe how his/her HS symptoms are now ("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)".
- Change from Baseline to Week 16 in Health Status Questionnaire (EQ-5D-3L) [Baseline (Week 0) to Week 16]
The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.
- Change from Baseline to Week 12 in Health Statues Questionnaire (EQ-5D-3L) [Baseline (Week 0) to Week 12]
The EQ-5D-3L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.
- Change from Baseline to Week 16 in Work Productivity and Activity Impairment (WPAI) Questionnaire [Baseline (Week 0) to Week 16]
To measure the effect of general health and symptom severity on work productivity and regular activities during the past seven days.
- Change from Baseline to Week 12 in Work Productivity and Activity Impairment (WPAI) Questionnaire [Baseline (Week 0) to Week 12]
To measure the effect of general health and symptom severity on work productivity and regular activities during the past seven days.
- Assessment of bermekimab Pharmacokinetics (PK) [Pre-Dose Collection at Baseline (Week 0), Weeks 1, 2, 3, 4, 5, 8, 16, 4 weeks post-final dose collection (Week 20) and 8 weeks post-final dose collection (Week 24)]
An enzyme-linked immunosorbent assay (ELISA) has been developed to specifically measure bermekimab levels in human plasma. The PK samples will also be used to test for the presence of antibodies against bermekimab.
- Reduction in serum IL-6 from Baseline to Week 16 [Baseline (Week 0) to Week 16]
The IL-6 samples will be used to test for change in serum IL-6 levels in patients, which has shown to correlate with disease severity in HS and potentially a more reliable predictor of treatment response in HS patients than CRP
- Reduction in serum IL-6 from Baseline to Week 12 [Baseline (Week 0) to Week 12]
The IL-6 samples will be used to test for change in serum IL-6 levels in patients, which has shown to correlate with disease severity in HS and potentially a more reliable predictor of treatment response in HS patients than CRP
- Reduction in serum IL-6 from Baseline to Week 8 [Baseline (Week 0) to Week 8]
The IL-6 samples will be used to test for change in serum IL-6 levels in patients, which has shown to correlate with disease severity in HS and potentially a more reliable predictor of treatment response in HS patients than CRP
- Change from Baseline to Week 16 in Hidradenitis Suppurativa Symptom Diary (HSSD) total symptom score [Baseline (Week 0) to Week 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 are 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. Each individual symptom scale score, ranging from 0-10 will be summarized. A total symptom score, which will also range from 0-10, will be derived by averaging the 5 individual scale scores that utilize the past 7-day recall period with higher score indicates more severe disease.
- Change from Baseline to Week 12 in Hidradenitis Suppurativa Symptom Diary (HSSD) total symptom score [Baseline (Week 0) to Week 12]
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 are 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. Each individual symptom scale score, ranging from 0-10 will be summarized. A total symptom score, which will also range from 0-10, will be derived by averaging the 5 individual scale scores that utilize the past 7-day recall period with higher score indicates more severe disease.
Eligibility Criteria
Criteria
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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Desert Sky | Gilbert | Arizona | United States | 85295 |
| 2 | Marvel Clinical Research | Huntington Beach | California | United States | 92647 |
| 3 | University of Southern California | Los Angeles | California | United States | 90033 |
| 4 | Dermatology Research Associates | Los Angeles | California | United States | 90045 |
| 5 | Syrentis Clinical Research | Santa Ana | California | United States | 92705 |
| 6 | Wolverine Clinical Trials | Santa Ana | California | United States | 92705 |
| 7 | Visionary Investigators Network | Aventura | Florida | United States | 33180 |
| 8 | Florida Academic Dermatology Centers | Coral Gables | Florida | United States | 33134 |
| 9 | Doral Medical Research | Doral | Florida | United States | 33166 |
| 10 | Floridian Research Institute | Miami | Florida | United States | 33145 |
| 11 | Florida International Medical Research | Miami | Florida | United States | 33155 |
| 12 | P&S Research, LLC | Miami | Florida | United States | 33175 |
| 13 | Accel Clinical Research | Orlando | Florida | United States | 32819 |
| 14 | Physica Clinical Research | Sebastian | Florida | United States | 32958 |
| 15 | Avita Clinical Research | Tampa | Florida | United States | 33613 |
| 16 | Forcare Clinical Research, Inc. | Tampa | Florida | United States | 33613 |
| 17 | Integrated Clincal Research LLC | West Palm Beach | Florida | United States | 33406 |
| 18 | Columbus Regional Research Institute | Columbus | Georgia | United States | 31904 |
| 19 | Advanced Medical Research | Sandy Springs | Georgia | United States | 30328 |
| 20 | Meridian Clinical Research, LLC | Savannah | Georgia | United States | 31406 |
| 21 | Dawes Fretzin Clinical Research Group | Indianapolis | Indiana | United States | 46256 |
| 22 | Randall Dermatology & Cosmetic Surgery | West Lafayette | Indiana | United States | 47906 |
| 23 | Meridian Clinical Research, LLC | Baton Rouge | Louisiana | United States | 70808 |
| 24 | Clinical Trials of SWLA | Lake Charles | Louisiana | United States | 70605 |
| 25 | Oakland Hills Dermatology | Auburn Hills | Michigan | United States | 48326 |
| 26 | Revival Research Institute, LLC | Troy | Michigan | United States | 48084 |
| 27 | Washington University in St. Louis | Saint Louis | Missouri | United States | 63130 |
| 28 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 29 | University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
| 30 | ClinOhio Research Services | Columbus | Ohio | United States | 43213 |
| 31 | Clinical Research Solutions, LLC | Milan | Tennessee | United States | 38358 |
| 32 | Progressive Clinical Research | San Antonio | Texas | United States | 78213 |
| 33 | Dominion Medical Associates, Inc. | Richmond | Virginia | United States | 23233 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108834
- 77474462HDS2002