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

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

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

Study Overview

• Status: Completed
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Biological: adalimumab; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2400
    • Site Ref # / Investigator 18683
  • Roskilde, Denmark, 4000
    • Site Ref # / Investigator 18684
• Germany
  • Dessau, Germany, 06847
    • Site Ref # / Investigator 18471
  • Kiel, Germany, 24105
    • Site Ref # / Investigator 18469
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Site Ref # / Investigator 18470
  • Rotterdam, Netherlands, 3015 CA
    • Site Ref # / Investigator 18468
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Site Ref # / Investigator 19062
  • California
    • Bakerfield, California, United States, 93309
      • Site Ref # / Investigator 18201
    • Los Angeles, California, United States, 90045
      • Site Ref # / Investigator 18467
    • San Diego, California, United States, 92103
      • Site Ref # / Investigator 18207
  • Florida
    • Miami, Florida, United States, 33136
      • Site Ref # / Investigator 18204
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Site Ref # / Investigator 18209
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Site Ref # / Investigator 18202
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Site Ref # / Investigator 18211
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Site Ref # / Investigator 18203
    • Boston, Massachusetts, United States, 02114
      • Site Ref # / Investigator 18210
  • Missouri
    • St Louis, Missouri, United States, 63104
      • Site Ref # / Investigator 18461
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Site Ref # / Investigator 18466
  • New York
    • New York, New York, United States, 10016
      • Site Ref # / Investigator 19141
    • New York, New York, United States, 10019
      • Site Ref # / Investigator 18208
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Site Ref # / Investigator 19001
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Site Ref # / Investigator 18981
    • Philadelphia, Pennsylvania, United States, 19104
      • Site Ref # / Investigator 18464
  • Texas
    • Dallas, Texas, United States, 75246-1613
      • Site Ref # / Investigator 19061
    • San Antonio, Texas, United States, 78258
      • Site Ref # / Investigator 18463
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Site Ref # / Investigator 18206

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adalimumab 40 mg qwk; 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; Subcutaneous injection using prefilled syringe containing adalimumab 40 mg in 0.8 milliliters; Other Names: ABT-D2E7; Humira
Experimental: Adalimumab 40 mg eow; 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; Subcutaneous injection using prefilled syringe containing adalimumab 40 mg in 0.8 milliliters; Other Names: ABT-D2E7; Humira
Placebo Comparator: Placebo; Matching placebo for adalimumab, administered weekly starting at Week 0 through Week 15.	Drug: Placebo; Subcutaneous injection using prefilled syringe containing 0.8 milliliters

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Martin Okun, MD, PhD, Abbott

Publications and helpful links

General Publications

• Ryan C, Sobell JM, Leonardi CL, Lynde CW, Karunaratne M, Valdecantos WC, Hendrickson BA. Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients with Hidradenitis Suppurativa or Psoriasis. Am J Clin Dermatol. 2018 Jun;19(3):437-447. doi: 10.1007/s40257-017-0341-6.
• Scheinfeld N, Sundaram M, Teixeira H, Gu Y, Okun M. Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial. Dermatol Online J. 2016 Mar 16;22(3):13030/qt38x5922j.
• Kimball AB, Kerdel F, Adams D, Mrowietz U, Gelfand JM, Gniadecki R, Prens EP, Schlessinger J, Zouboulis CC, van der Zee HH, Rosenfeld M, Mulani P, Gu Y, Paulson S, Okun M, Jemec GB. Adalimumab for the treatment of moderate to severe Hidradenitis suppurativa: a parallel randomized trial. Ann Intern Med. 2012 Dec 18;157(12):846-55. doi: 10.7326/0003-4819-157-12-201212180-00004.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: April 30, 2009
• First Submitted That Met QC Criteria: June 10, 2009
• First Posted (Estimate): June 11, 2009

Study Record Updates

• Last Update Posted (Estimate): May 9, 2011
• Last Update Submitted That Met QC Criteria: April 14, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Abscess; Fistula; Adalimumab; Nodule; Hidradenitis Suppurativa; Physicians Global Assessment; Hurley Stage; Sartorius Scale
• Additional Relevant MeSH Terms: Sweat Gland Diseases; Skin Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Suppuration; Skin Diseases, Bacterial; Hidradenitis Suppurativa; Hidradenitis; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M10-467; 2008-004587-38 (EudraCT Number)