Hidradenitis Suppurativa (HS)
Conditions
Keywords
Hidradenitis Suppurativa, Axilla, Inguinal region, Hurley Stage I, II, or III, Adalimumab, Secondary intention, Abcess and inflammatory nodule (AN) count
Brief summary
The objective of this study was to assess the safety and efficacy of adalimumab prior to surgery in participants with moderate to severe Hidradenitis Suppurativa (HS) who were surgical candidates.
Detailed description
This was an interventional, randomized, double-blind (DB), placebo-controlled study. The study duration included a 30-day Screening Period, an initial 12-week DB treatment pre-surgery period (Period A), a 2-week peri-operative period with continuation of weekly DB study drug administration (Period B), and a subsequent 10-week DB treatment post-operative period (Period C). Randomization (in a 1:1 ratio) in Period A was stratified by baseline Hurley Stage (II versus III) and anatomical location of the planned surgical site (i.e., axilla versus inguinal region). The projected size of the surgical excision established by the designated surgeon during the Screening Period (calculated from a tracing of the outer perimeter onto an acetate sheet or equivalent) was recorded. In Period B, the designated surgeon measured and recorded the surface area of the actual surgery, with surgery occurring during Week 13. Surgery and post-operative management (e.g., hospitalization, surgical wound care) was per local practice. No study drug was administered at Week 24, the final study visit. Participants were able to begin commercial product (as prescribed by the participants's physician) after all Week 24 procedures were completed.
Interventions
DRUGPlacebo
Subcutaneous injections administered as described in arm description
DRUGAdalimumab
Subcutaneous injections administered as described in arm description
Sponsors
AbbVie
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Participant must have skin lesions that are diagnostic of Hidradenitis Suppurativa (HS) for at least 1 year (365 days) prior to the Baseline visit * Participant must have at least 3 distinct anatomical regions involved with inflammatory (also termed 'active') HS lesions; plus * either one axilla or one inguinal region (limited to the inguino-crural fold and adjacent areas) that requires excisional surgery, and * with at least one of the other affected HS regions (e.g., contralateral inguinal region, buttocks, inframammary region) rated as Hurley Stage II or III * Participant must have a total abscess and inflammatory nodule (AN) count of greater than or equal to 3 at the Baseline visit within the HS non-surgical sites * The HS surgical site must contain at least one active HS lesion * The HS surgical site must require excisional surgery and is large enough to require healing by secondary intention as assessed by the designated surgeon
Exclusion criteria
* Participant has a draining fistula count of greater than 20 at the Baseline visit * Participant requires surgery at any anatomical site other than an unilateral axilla or inguinal region site * Participant requires surgical management prior to Week 13 * Participant requires, based on the designated surgeon's assessment, excisional surgery with primary closure as the method of closure being most beneficial for the participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | At Week 12 | HiSCR is defined as at least a 50% reduction in the abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving HiSCR-es at Week 12 | At Week12 | Hidradenitis Suppurativa Clinical Response-es (HiSCR-es) is defined as at least a 50% reduction in the abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline, excluding the Hidradenitis Suppurativa surgical site. |
| Percentage of Participants Achieving HiSCR-es at Week 24 | At Week 24 | Hidradenitis Suppurativa Clinical Response-es (HiSCR-es) is defined as at least a 50% reduction in the abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline, excluding the Hidradenitis Suppurativa surgical site. |
| Percent Change in the Surface Area of the Hidradenitis Suppurativa (HS) Surgical Site From Baseline to Week 12 | From Baseline to Week 12 | The projected size of the surgical excision established by the designated surgeon during the Screening Period (calculated from a tracing of the outer perimeter onto an acetate sheet or equivalent) was recorded by the study physician. The change in the surface area of the projected HS surgical site from Baseline to Week 12 was documented. |
| Percentage of Participants at Week 12 That Require a Less Extensive Surgery Than the Surgical Plan (Determined at Baseline) or No Surgery | At Week 12 | The projected size of the surgical excision established by the designated surgeon during the Screening Period (calculated from a tracing of the outer perimeter onto an acetate sheet or equivalent) was recorded by the study physician. The change in the surface area of the projected HS surgical site from Baseline to Week 12 was documented, and the percentage of participants at Week 12 requiring a less extensive surgery than the surgical plan (determined at Baseline) or no surgery as determined by the designated surgeon was recorded. |
Countries
Belgium, Canada, Colombia, Czechia, Denmark, France, Germany, Greece, Ireland, Italy, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russia, Saudi Arabia, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit
Participants by arm
| Arm | Count |
|---|---|
| Placebo Period A: Day 1- 4 subcutaneous (SC) injections; Week 2- 2 SC injections; Weeks 4-12- 1 SC injection each week
Period B: Weeks 13-14- 1 SC injection each week
Period C: Weeks 15-23- 1 SC injection each week | 103 |
| Adalimumab Period A: Day 1- 4 subcutaneous (SC) 40 mg injections; Week 2- 2 SC 40 mg injections; Weeks 4-12- 1 SC 40 mg injection each week
Period B: Weeks 13-14- 1 SC 40 mg injection each week
Period C: Weeks 15-23- 1 SC 40 mg injection each week | 103 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Other, not specified | 5 | 1 |
| Overall Study | Planned HS surgery performed prior Wk 13 | 1 | 0 |
| Overall Study | Withdrew consent | 9 | 8 |
Baseline characteristics
| Characteristic | Placebo | Adalimumab | Total |
|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 10.81 | 38.5 years STANDARD_DEVIATION 11.71 | 37.6 years STANDARD_DEVIATION 11.27 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 97 Participants | 96 Participants | 193 Participants |
| Sex: Female, Male Female | 55 Participants | 51 Participants | 106 Participants |
| Sex: Female, Male Male | 48 Participants | 52 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 2 / 103 |
| other Total, other adverse events | 43 / 103 | 48 / 103 |
| serious Total, serious adverse events | 3 / 103 | 7 / 103 |
Outcome results
Primary
Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12
HiSCR is defined as at least a 50% reduction in the abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline.
Time frame: At Week 12
Population: Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit; non-responder imputation (NRI) was used for missing data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | 34.0 percentage of participants |
| Adalimumab | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | 47.6 percentage of participants |
p-value: =0.049Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving HiSCR-es at Week 12
Hidradenitis Suppurativa Clinical Response-es (HiSCR-es) is defined as at least a 50% reduction in the abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline, excluding the Hidradenitis Suppurativa surgical site.
Time frame: At Week12
Population: Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit; non-responder imputation (NRI) was used for missing data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving HiSCR-es at Week 12 | 35.0 percentage of participants |
| Adalimumab | Percentage of Participants Achieving HiSCR-es at Week 12 | 47.6 percentage of participants |
p-value: =0.067Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving HiSCR-es at Week 24
Hidradenitis Suppurativa Clinical Response-es (HiSCR-es) is defined as at least a 50% reduction in the abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline, excluding the Hidradenitis Suppurativa surgical site.
Time frame: At Week 24
Population: Intent-to-Treat (ITT) population: all participants who were randomized at the Baseline visit; non-responder imputation (NRI) was used for missing data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving HiSCR-es at Week 24 | 31.1 percentage of participants |
| Adalimumab | Percentage of Participants Achieving HiSCR-es at Week 24 | 51.5 percentage of participants |
p-value: =0.003Cochran-Mantel-Haenszel
Secondary
Percentage of Participants at Week 12 That Require a Less Extensive Surgery Than the Surgical Plan (Determined at Baseline) or No Surgery
The projected size of the surgical excision established by the designated surgeon during the Screening Period (calculated from a tracing of the outer perimeter onto an acetate sheet or equivalent) was recorded by the study physician. The change in the surface area of the projected HS surgical site from Baseline to Week 12 was documented, and the percentage of participants at Week 12 requiring a less extensive surgery than the surgical plan (determined at Baseline) or no surgery as determined by the designated surgeon was recorded.
Time frame: At Week 12
Population: Observed case (OC) analysis was performed on the intent-to-treat (ITT) population. The ITT population consisted of all participants who were randomized at the Baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants at Week 12 That Require a Less Extensive Surgery Than the Surgical Plan (Determined at Baseline) or No Surgery | 43.7 percentage of participants |
| Adalimumab | Percentage of Participants at Week 12 That Require a Less Extensive Surgery Than the Surgical Plan (Determined at Baseline) or No Surgery | 46.3 percentage of participants |
p-value: =0.746Cochran-Mantel-Haenszel
Secondary
Percent Change in the Surface Area of the Hidradenitis Suppurativa (HS) Surgical Site From Baseline to Week 12
The projected size of the surgical excision established by the designated surgeon during the Screening Period (calculated from a tracing of the outer perimeter onto an acetate sheet or equivalent) was recorded by the study physician. The change in the surface area of the projected HS surgical site from Baseline to Week 12 was documented.
Time frame: From Baseline to Week 12
Population: Observed case (OC) analysis was performed on the intent-to-treat (ITT) population. The ITT population consisted of all participants who were randomized at the Baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in the Surface Area of the Hidradenitis Suppurativa (HS) Surgical Site From Baseline to Week 12 | 26.233 percent change from Baseline |
| Adalimumab | Percent Change in the Surface Area of the Hidradenitis Suppurativa (HS) Surgical Site From Baseline to Week 12 | 68.190 percent change from Baseline |
p-value: =0.313ANCOVA