Efficacy and Safety Study of Adalimumab in Treatment of Hidradenitis Suppurativa

Study Overview
=================
Brief Summary
-----------------
A study to evaluate the safety and efficacy of treatment with adalimumab in adults with moderate to severe hidradenitis suppurativa (HS).

Detailed Description
-----------------
The clinical trial identifier is PIONEER I. The purpose of this study is to evaluate the safety of adalimumab and to determine how well it works in the treatment of adults with moderate to severe HS. HS is a chronic skin disease that creates red, swollen, painful bumps which can break open to combine and form tunnels in the skin and scars. Sometimes these bumps can heal themselves quickly and sometimes they will become much worse and create sores that heal with multiple combined scars, or areas that do not heal. In this study, approximately 300 adults will be enrolled at treatment centers worldwide. Subject participation in this study will be up to 50 weeks. There will be a screening period, which will last from 7 to 30 days, and a study treatment period of up to 36 weeks. Study visits occur at Screening, Baseline, and Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32 and 36 (or sooner if subject leaves the study before Week 36). The study is divided into two treatment periods. The first period (Period A) will last 12 weeks and the second period (Period B) will last up to 24 weeks.

Official Title
-----------------
A Phase 3 Multicenter Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Hidradenitis Suppurativa - PIONEER I

Conditions
-----------------
Hidradenitis Suppurativa (HS)

Intervention / Treatment
-----------------
* Biological: adalimumab
* Biological: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults must have a diagnosis of HS for at least 1 year prior to Baseline. HS lesions must be present in at least two distinct anatomical areas, one of which must be at least Hurley Stage II or Hurley Stage III. Subject must have stable HS for at least 60 days prior to Screening visit and at Baseline visit. Subject must have experienced an inadequate response to at least a 90-day treatment of oral antibiotics for treatment of HS. Subject must have a total AN count of greater than or equal to 3 at baseline. Exclusion Criteria: Subject was previously treated with adalimumab or another anti-tumor necrosis factor (anti-TNF) therapy (e.g., infliximab or etanercept). Subject received any oral antibiotic treatment for HS within 28 days prior to Baseline. Subject received oral concomitant analgesics (including opioids) for HS-related pain within 14 days prior to Baseline visit. If entering the study on concomitant oral analgesics for non-HS related pain: Subject on opioid analgesics within 14 days prior to Baseline visit; Subject not on a stable dose of non-opioid oral analgesics for at least 14 days prior to the Baseline visit (as needed is not considered a stable dose).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo for 12 weeks. | Biological: placebo<br>* Placebo pre-filled syringe, administered by subcutaneous injection<br>|
| Experimental: Adalimumab Every Week (EW)<br>Adalimumab ew for 12 weeks (160 mg at Week 0; 80 mg at Week 2; and 40 mg ew from Week 4 to Week 12). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: Humira;|
| Experimental: Placebo/Adalimumab Every Week (EW)<br>Participants randomized to receive placebo in Period 1 received adalimumab 160 mg at Week 12, 80 mg at Week 14, and 40 mg ew from Week 16 to Week 35 in Period 2 (up to 24 weeks). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: Humira;Biological: placebo<br>* Placebo pre-filled syringe, administered by subcutaneous injection<br>|
| Experimental: Adalimumab Every Week (EW)/Placebo<br>Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive placebo ew from Week 12 to Week 35 in Period 2 (up to 24 weeks). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: Humira;Biological: placebo<br>* Placebo pre-filled syringe, administered by subcutaneous injection<br>|
| Experimental: Adalimumab Every Week (EW)/ Adalimumab Every Other Week (EOW)<br>Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive adalimumab 40 mg eow from Week 12 to Week 35 in Period 2; placebo injections were administered eow from Week 13 to Week 35 (up to 24 weeks). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: Humira;|
| Experimental: Adalimumab Every Week (EW)/Adalimumab Every Week (EW)<br>Participants randomized to receive adalimumab ew in Period 1 were re-randomized to receive 40 mg adalimumab ew from Week 12 to Week 35 in Period 2 (up to 24 weeks). | Biological: adalimumab<br>* Adalimumab pre-filled syringe, administered by subcutaneous injection<br>* Other names: Humira;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | HiSCR was defined as at least a 50% reduction in abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count at Week 12 relative to Baseline. Data are presented for all participants and by baseline Hurley Stage (Stage 1: Abscess formation, single or multiple, without sinus tracts and scarring; Stage II: One or more widely separated recurrent abscesses with tract formation and scars. A participant with at least 1 anatomic region with Hurley Stage II disease and with no anatomic regions with Hurley Stage III disease was classified as Hurley Stage II; and Stage III: Multiple interconnected tracts and abscesses across the entire area, with diffuse or near diffuse involvement. A participant with at least 1 anatomic region with Hurley Stage III disease was classified as Hurley Stage III). Non-responder imputation (NRI): Participants with missing data were considered non-responders. | Baseline (Week 0) up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Baseline Hurley Stage II Who Achieved Abscess and Inflammatory Nodule (AN) Count of 0, 1, or 2 at Week 12 | The percentage of participants with AN counts lowered to 0, 1, or 2 at Week 12 among participants with Hurley Stage II at Baseline. NRI: Participants with missing data were considered non-responders. | Baseline (Week 0) up to Week 12 | 
| Percentage of Participants Achieving At Least 30% Reduction and At Least 1 Unit Reduction From Baseline in Patient's Global Assessment of Skin Pain (NRS30) - At Worst at Week 12 Among Participants With Baseline Skin Pain NRS ≥ 3 | The Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS) was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the last 24 hours. The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the Patient's Global Assessment of Skin Pain (NRS30) - at worst at Week 12 among participants with Baseline NRS ≥ 3 are presented. Weekly averages of daily assessments were analyzed. NRI: Participants with missing data were considered non-responders. | Baseline (Week 0) up to Week 12 | 
| Change From Baseline to Week 12 in Modified Sartorius Score | The Sartorius Scale 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 Sartorius score is the sum of the 12 regional scores. Last Observation Carried Forward (LOCF): The last completed evaluation from the previous visit within the particular period for efficacy measures was carried forward to impute missing data at later visits in the same period. Baseline efficacy evaluations were not carried forward. | Baseline (Week 0) and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HS, acne, psoriasis, hidradenitis suppurativa, TNF, PIONEER I, acne inversa, boil, placebo controlled, Double blind, adalimumab