Study of Adalimumab in Subjects With Moderate to Severe Chronic Hidradenitis Suppurativa

Study Overview
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Brief Summary
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This study will investigate how well adalimumab works in people with hidradenitis suppurativa (HS) in the short and long term.

Detailed Description
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This Phase 2 randomized, double-blind, placebo-controlled multicenter study consists of 2 treatment periods: a 16-week double-blind, placebo-controlled period (Period 1: Weeks 0 through the end of Week 15) followed by a 36-week open-label period (Period 2: Weeks 16 through 52). Participants are randomized in a 1:1:1 ratio based on Hurley Stage as stratification factor to receive adalimumab 40 mg every week (qwk), adalimumab 40 mg every other week (eow), or matching placebo during Period 1. During Period 2, participants receive open-label adalimumab 40 mg eow with the option to escalate to 40 mg weekly dosing at Week 28 or Week 31 if the participant has a Physician's Global Assessment of moderate disease or worse (score of greater than or equal to 3). The primary objective of the study is to determine the clinical efficacy and safety of participants with moderate to severe chronic hidradenitis suppurativa (HS) after 16 weeks of treatment. The secondary objective is to evaluate the maintenance of efficacy and continued safety of adalimumab for an additional 36 weeks of treatment. (Note: Hurley Stage is a classification system for skin involvement that is largely based on the presence and extent of abscess formation accompanied by scarring and sinus tracts. Hurley Stages are I [abscess formation without scarring and sinus tracts], II [widely separated recurrent abscesses with scarring and sinus tracts], and III [multiple interconnected abscesses and sinus tracts across entire area]. Randomization in this study was performed using stratification by Hurley Stage [III versus (I or II).) At the present time, Period 1 double-blind data only is provided; additional information will be provided when analysis of open-label Period 2 is completed.

Official Title
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A Phase 2 Multicenter Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Chronic Hidradenitis Suppurativa

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Biological: adalimumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with stable, moderate to severe hidradenitis suppurativa Negative Chest X-ray and PPD test at Screening. If participant has had a past ulcerative reaction to PPD placement and/or chest X-ray consistent with prior tuberculosis exposure, the participant must initiate, or have documented completion of, a course of anti-tuberculosis therapy. Ability to administer subcutaneous injections General good health otherwise Exclusion Criteria: Prior anti-TNF therapy Unstable antibiotic therapy for HS Required medication washouts for other HS treatments Prior exposure to Tysabri® (natalizumab); Recent infection requiring treatment Significant medical events or conditions that may put patients at risk for participation Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study; History of cancer, except successfully treated skin cancer Recent history of drug or alcohol abuse

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 |
| --- | --- |
| Experimental: Adalimumab 40 mg qwk<br>Initial dose of adalimumab 160 mg at Week 0, adalimumab 80 mg at Week 2, followed by 40 mg weekly (qwk) starting at Week 4 through Week 15. | Biological: adalimumab<br>* Subcutaneous injection using prefilled syringe containing adalimumab 40 mg in 0.8 milliliters<br>* Other names: Humira;|
| Experimental: Adalimumab 40 mg eow<br>Initial dose of adalimumab 80 mg at Week 0, followed by adalimumab 40 mg eow (every other week) starting at Week 1 through Week 15. | Biological: adalimumab<br>* Subcutaneous injection using prefilled syringe containing adalimumab 40 mg in 0.8 milliliters<br>* Other names: Humira;|
| Placebo Comparator: Placebo<br>Matching placebo for adalimumab, administered weekly starting at Week 0 through Week 15. | Drug: Placebo<br>* Subcutaneous injection using prefilled syringe containing 0.8 milliliters<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Response at Week 16 | Clinical response is defined as a Physician's Global Assessment (PGA) of clear, minimal, or mild (scores of 0, 1, or 2) with a minimum of 2 grades improvement (reduction) from baseline. PGA is a physician's assessment of the severity of disease based on a 6-point scale (score of 0 = clear and 5 = very severe). | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 16 | Includes inflammatory nodules that are tender, erythematous, and have diameters less than 5 cm and includes plaques that have diameters greater than or equal to 5 cm. Range for percent change is negative infinity to infinity. Negative percent changes from Baseline indicate improvement. | Baseline, Week 16 | 
| Percentage of Participants Achieving Clinical Response at Week 2 | Clinical response is defined as a Physician's Global Assessment (PGA) of clear, minimal, or mild (scores of 0, 1, or 2) with a minimum of 2 grades improvement (reduction) from baseline. PGA is a physician's assessment of the severity of disease based on a 6-point scale (score of 0 = clear and 5 = very severe). | Baseline, Week 2 | 
| Percentage of Participants Achieving Clinical Response at Week 4 | Clinical response is defined as a Physician's Global Assessment (PGA) of clear, minimal, or mild (scores of 0, 1, or 2) with a minimum of 2 grades improvement (reduction) from baseline. PGA is a physician's assessment of the severity of disease based on a 6-point scale (score of 0 = clear and 5 = very severe). | Baseline, Week 4 | 
| Percentage of Participants Achieving Clinical Response at Week 8 | Clinical response is defined as a Physician's Global Assessment (PGA) of clear, minimal, or mild (scores of 0, 1, or 2) with a minimum of 2 grades improvement (reduction) from baseline. PGA is a physician's assessment of the severity of disease based on a 6-point scale (score of 0 = clear and 5 = very severe). | Baseline, Week 8 | 
| Percentage of Participants Achieving Clinical Response at Week 12 | Clinical response is defined as a Physician's Global Assessment (PGA) of clear, minimal, or mild (scores of 0, 1, or 2) with a minimum of 2 grades improvement (reduction) from baseline. PGA is a physician's assessment of the severity of disease based on a 6-point scale (score of 0 = clear and 5 = very severe). | Baseline, Week 12 | 
| Change From Baseline in Modified Sartorius Scale at Week 16 | The Modified Sartorius Scale reflects changes in hidradenitis suppurative symptoms, namely the number of lesions (abscesses, nodules, and fistulas) and the longest distance between lesions. A total score is derived based on assessments at up to 8 distinct anatomical regions and ranges from 5 to indefinite. Smaller numbers are better scores and indicate less lesion involvement, thus decreases (negative changes) from baseline indicate improvement in severity of disease. | Baseline, Week 16 | 
| Change From Baseline in Modified Sartorius Scale at Week 52 | The Modified Sartorius Scale reflects changes in hidradenitis suppurative symptoms, namely the number of lesions (abscesses, nodules, and fistulas) and the longest distance between lesions. A total score is derived based on assessments at up to 8 distinct anatomical regions and ranges from 5 to indefinite. Smaller numbers are better scores and indicate less lesion involvement, thus decreases (negative changes) from baseline indicate improvement in severity of disease. | Baseline, Week 52 | 
| Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 52 | Includes inflammatory nodules that are tender, erythematous, and have diameters less than 5 cm and includes plaques that have diameters greater than or equal to 5 cm. Range for percent change is negative infinity to infinity. Negative percent changes from Baseline indicate improvement. | Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hidradenitis Suppurativa, Adalimumab, Nodule, Abscess, Fistula, Physicians Global Assessment, Hurley Stage, Sartorius Scale