Hidradenitis Suppurativa
Conditions
Keywords
Hidradenitis Suppurativa, Adalimumab, Nodule, Abscess, Fistula, Physicians Global Assessment, Hurley Stage, Sartorius Scale
Brief summary
This study will investigate how well adalimumab works in people with hidradenitis suppurativa (HS) in the short and long term.
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.
Interventions
BIOLOGICALadalimumab
Subcutaneous injection using prefilled syringe containing adalimumab 40 mg in 0.8 milliliters
DRUGPlacebo
Subcutaneous injection using prefilled syringe containing 0.8 milliliters
Sponsors
Abbott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Response at Week 16 | Baseline, 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Response at Week 2 | Baseline, 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). |
| Percentage of Participants Achieving Clinical Response at Week 4 | Baseline, 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). |
| Percentage of Participants Achieving Clinical Response at Week 8 | Baseline, 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). |
| Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 16 | Baseline, 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. |
| Change From Baseline in Modified Sartorius Scale at Week 16 | Baseline, 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. |
| Change From Baseline in Modified Sartorius Scale at Week 52 | Baseline, 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. |
| Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 52 | Baseline, 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. |
| Percentage of Participants Achieving Clinical Response at Week 12 | Baseline, 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). |
Countries
Denmark, Germany, Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab 40 mg Qwk DB Loading 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. | 51 |
| Adalimumab 40 mg Eow DB Loading dose of adalimumab 80 mg at Week 0, followed by adalimumab 40 mg eow (every other week) starting at Week 1 through Week 15. | 52 |
| Placebo DB Matching placebo for adalimumab, administered weekly starting at Week 0 through Week 15. | 51 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Exceeded allowed number of interventions | 0 | 0 | 1 |
| Overall Study | Investigator discretion | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 2 |
| Overall Study | Non-compliance | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Adalimumab 40 mg Qwk DB | Adalimumab 40 mg Eow DB | Placebo DB | Total |
|---|---|---|---|---|
| Age Continuous | 35.1 years STANDARD_DEVIATION 10.69 | 36.1 years STANDARD_DEVIATION 12.5 | 37.8 years STANDARD_DEVIATION 12.1 | 36.3 years STANDARD_DEVIATION 11.76 |
| Region of Enrollment Europe | 10 participants | 13 participants | 15 participants | 38 participants |
| Region of Enrollment United States | 41 participants | 39 participants | 36 participants | 116 participants |
| Sex: Female, Male Female | 36 Participants | 38 Participants | 36 Participants | 110 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 15 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 36 / 51 | 33 / 52 | 30 / 51 |
| serious Total, serious adverse events | 4 / 51 | 3 / 52 | 2 / 51 |
Outcome results
Primary
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).
Time frame: Baseline, Week 16
Population: Intent-to-treat analysis with non-responder imputation (participants with missing PGA scores counted as non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 40 mg Qwk DB | Percentage of Participants Achieving Clinical Response at Week 16 | 17.6 percentage of participants |
| Adalimumab 40 mg Eow DB | Percentage of Participants Achieving Clinical Response at Week 16 | 9.6 percentage of participants |
| Placebo DB | Percentage of Participants Achieving Clinical Response at Week 16 | 3.9 percentage of participants |
p-value: 0.022Cochran-Mantel-Haenszel
p-value: 0.025Cochran-Mantel-Haenszel
p-value: 0.252Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Week 16
Population: Population was Intent-to-treat (ITT). Imputation method was Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Adalimumab 40 mg Qwk DB | Change From Baseline in Modified Sartorius Scale at Week 16 | -30.0 scores on a scale | Inter-Quartile Range 53.82 |
| Adalimumab 40 mg Eow DB | Change From Baseline in Modified Sartorius Scale at Week 16 | -16.0 scores on a scale | Inter-Quartile Range 82.54 |
| Placebo DB | Change From Baseline in Modified Sartorius Scale at Week 16 | -7.5 scores on a scale | Inter-Quartile Range 47.78 |
p-value: 0.045Van Elteren test
p-value: 0.014Van Elteren test
p-value: 0.169Van Elteren test
Secondary
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.
Time frame: Baseline, Week 52
Secondary
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).
Time frame: Baseline, Week 12
Population: Intent-to-treat analysis with non-responder imputation (participants with missing PGA scores counted as non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 40 mg Qwk DB | Percentage of Participants Achieving Clinical Response at Week 12 | 21.6 percentage of participants |
| Adalimumab 40 mg Eow DB | Percentage of Participants Achieving Clinical Response at Week 12 | 7.7 percentage of participants |
| Placebo DB | Percentage of Participants Achieving Clinical Response at Week 12 | 5.9 percentage of participants |
p-value: 0.012Cochran-Mantel-Haenszel
p-value: 0.02Cochran-Mantel-Haenszel
p-value: 0.721Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline, Week 2
Population: Intent-to-treat analysis with non-responder imputation (participants with missing PGA scores counted as non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 40 mg Qwk DB | Percentage of Participants Achieving Clinical Response at Week 2 | 2.0 percentage of participants |
| Adalimumab 40 mg Eow DB | Percentage of Participants Achieving Clinical Response at Week 2 | 9.6 percentage of participants |
| Placebo DB | Percentage of Participants Achieving Clinical Response at Week 2 | 2.0 percentage of participants |
p-value: 1Cochran-Mantel-Haenszel
p-value: 1Cochran-Mantel-Haenszel
p-value: 0.097Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline, Week 4
Population: Intent-to-treat analysis with non-responder imputation (participants with missing PGA scores counted as non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 40 mg Qwk DB | Percentage of Participants Achieving Clinical Response at Week 4 | 11.8 percentage of participants |
| Adalimumab 40 mg Eow DB | Percentage of Participants Achieving Clinical Response at Week 4 | 5.8 percentage of participants |
| Placebo DB | Percentage of Participants Achieving Clinical Response at Week 4 | 2.0 percentage of participants |
p-value: 0.044Cochran-Mantel-Haenszel
p-value: 0.051Cochran-Mantel-Haenszel
p-value: 0.32Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline, Week 8
Population: Intent-to-treat analysis with non-responder imputation (participants with missing PGA scores counted as non-responders).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab 40 mg Qwk DB | Percentage of Participants Achieving Clinical Response at Week 8 | 7.8 percentage of participants |
| Adalimumab 40 mg Eow DB | Percentage of Participants Achieving Clinical Response at Week 8 | 5.8 percentage of participants |
| Placebo DB | Percentage of Participants Achieving Clinical Response at Week 8 | 7.8 percentage of participants |
p-value: 1Cochran-Mantel-Haenszel
p-value: 1Cochran-Mantel-Haenszel
p-value: 0.673Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Week 16
Population: Population was Intent-to-treat (ITT) and included participants with any inflammatory nodules (defined as tender, erythematous) or plaques at Baseline. Imputation method was Last Observation Carried Forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Adalimumab 40 mg Qwk DB | Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 16 | -50.66 percent change | Standard Error 11.364 |
| Adalimumab 40 mg Eow DB | Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 16 | -30.43 percent change | Standard Error 11.452 |
| Placebo DB | Percent Change From Baseline in Number of All Inflammatory Nodules and Plaques at Week 16 | -13.66 percent change | Standard Error 11.452 |
p-value: 0.062ANCOVA
p-value: 0.019ANCOVA
p-value: 0.286ANCOVA
Secondary
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.
Time frame: Baseline, Week 52