Hidradenitis Suppurativa (HS)
Conditions
Keywords
Hidradenitis suppurativa (HS), Upadacitinib
Brief summary
Hidradenitis suppurativa (HS) is an inflammatory skin disease that causes painful lesions in the axilla (underarm), inguinal (groin) and anogenital (anal and genital) regions. This study will evaluate how well upadacitinib compared to placebo (no medicine) works to treat hidradenitis suppurativa in adult participants with moderate to severe disease. The study will assess change in disease signs and symptoms.
Detailed description
Upadacitinib is an investigational drug being developed for the treatment of HS. This study is double-blinded, which means that neither the trial participants nor the study doctors will know who will be given study drug and who will receive placebo (no medicine). Participants are randomly (by chance) put into 1 of 2 groups, called treatment arms. They are randomized in a 2 to 1 ratio meaning more participants have a chance to receive upadacitinib compared to placebo. Participants will undergo approximately 35-days of screening followed by a 48-week treatment period and a 30-day follow-up visit after the last dose of study drug for a total study duration of up to 57 weeks. The treatment period will consist of a 12-week placebo-controlled, double-blind period (Period 1) and a 36-week blinded extension period (Period 2). There may be a higher burden for participants in this trial compared to their standard of care. Participants will attend visits every other week, once a month, or once every 2 months during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGUpadacitinib
Tablet; Oral
DRUGPlacebo
Tablet; Oral
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of hidradenitis suppurativa (HS) for at least 1 year prior to Baseline. * Total abscess and inflammatory nodule (AN) count of ≥ 5 at Baseline, presence of HS lesions in at least 2 distinct anatomical areas, and draining fistula count of ≤ 20 at Baseline. * History of inadequate response or an intolerance to adequate trial of oral antibiotics for treatment of HS. * Required to use a daily antiseptic wash on HS lesions.
Exclusion criteria
-History of active skin disease (other than HS) that could interfere with assessment of HS, including skin infections requiring systemic treatment within 4 weeks of the Baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | Baseline and Week 12 | HiSCR is defined as at least a 50% reduction in the total 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 PGA Skin Pain Numeric Rating Scale 30 (NRS30) Response at Week 12 Among Participants With Baseline NRS ≥ 3 | Baseline and Week 12 | The Patient's Global Assessment (PGA) of Skin Pain Numeric Rating Scale (NRS) was used to assess the worst skin pain due to HS. Participants were asked to rate their worst skin pain in the last 24 hours on an 11-point numerical rating scale ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine) on a daily basis using an electronic diary. The weekly average score was calculated based on the daily scores from the 7 days prior to the visit (with non-missing values in 4 or more days of the 7 day period). NRS30 is defined as the percentage of participants who achieved at least a 30% reduction and at least 1 unit reduction from Baseline in the PGA of skin pain NRS in participants with Baseline skin pain NRS ≥ 3. |
Countries
Canada, Japan, Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at 21 study sites in 3 countries (Canada, Japan, and United States/Puerto Rico).
Pre-assignment details
Participants were randomized to upadacitinib or placebo in a 2:1 ratio. Randomization was stratified by anti-tumor necrosis factor (TNF) use prior to Baseline (yes or no) and Hurley stage (\< III or III).
Participants by arm
| Arm | Count |
|---|---|
| Placebo / Upadacitinib 15 mg Participants received matching placebo orally once a day for 12 weeks (Period 1) followed by 15 mg upadacitinib orally once a day for 36 weeks (Period 2). | 21 |
| Upadacitinib 30 mg Participants received 30 mg upadacitinib orally once a day for 12 weeks (Period 1) followed by 30 mg upadacitinib orally once a day for 36 weeks (Period 2). | 47 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 (Weeks 1-12) | Adverse Event | 1 | 0 |
| Period 1 (Weeks 1-12) | Lack of Efficacy | 0 | 1 |
| Period 1 (Weeks 1-12) | Lost to Follow-up | 0 | 2 |
| Period 1 (Weeks 1-12) | Other | 0 | 1 |
| Period 1 (Weeks 1-12) | Withdrawal by Subject | 1 | 2 |
| Period 2 (Weeks 12-48) | Lack of Efficacy | 2 | 3 |
| Period 2 (Weeks 12-48) | Lost to Follow-up | 1 | 2 |
| Period 2 (Weeks 12-48) | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Placebo / Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|
| Abscess and Inflammatory Nodule (AN) Count | 19.8 abscesses and inflammatory nodules STANDARD_DEVIATION 12.87 | 23.2 abscesses and inflammatory nodules STANDARD_DEVIATION 24.64 | 22.1 abscesses and inflammatory nodules STANDARD_DEVIATION 21.65 |
| Abscess Lesion Count | 4.0 abscess lesions STANDARD_DEVIATION 3.29 | 4.8 abscess lesions STANDARD_DEVIATION 6.39 | 4.6 abscess lesions STANDARD_DEVIATION 5.6 |
| Age, Continuous | 36.6 years STANDARD_DEVIATION 12.49 | 36.7 years STANDARD_DEVIATION 11.7 | 36.6 years STANDARD_DEVIATION 11.85 |
| Age, Customized 40 - < 65 years | 5 Participants | 17 Participants | 22 Participants |
| Age, Customized < 40 years | 15 Participants | 29 Participants | 44 Participants |
| Age, Customized ≥ 65 years | 1 Participants | 1 Participants | 2 Participants |
| Draining Fistula Lesion Count | 4.3 draining fistula lesions STANDARD_DEVIATION 6.17 | 3.4 draining fistula lesions STANDARD_DEVIATION 4.74 | 3.7 draining fistula lesions STANDARD_DEVIATION 5.19 |
| Duration of Hidradenitis Suppurativa (HS) Disease | 9.83 years STANDARD_DEVIATION 4.99 | 11.52 years STANDARD_DEVIATION 9.401 | 11.00 years STANDARD_DEVIATION 8.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 38 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hurley Stage Stage I | 1 Participants | 0 Participants | 1 Participants |
| Hurley Stage Stage II | 11 Participants | 24 Participants | 35 Participants |
| Hurley Stage Stage III | 9 Participants | 23 Participants | 32 Participants |
| Inflammatory Nodule Lesion Count | 15.7 nodule lesions STANDARD_DEVIATION 12.77 | 18.4 nodule lesions STANDARD_DEVIATION 20.98 | 17.6 nodule lesions STANDARD_DEVIATION 18.78 |
| Patient's Global Assessment (PGA) of Skin Pain Score | 4.852 units on a scale STANDARD_DEVIATION 3.3237 | 4.987 units on a scale STANDARD_DEVIATION 2.712 | 4.945 units on a scale STANDARD_DEVIATION 2.8879 |
| PGA Skin Pain Score In Participants with a Baseline Value ≥ 3 | 7.168 units on a scale STANDARD_DEVIATION 2.0395 | 6.180 units on a scale STANDARD_DEVIATION 2.1107 | 6.444 units on a scale STANDARD_DEVIATION 2.1155 |
| Prior Exposure to Tumor Necrosis Factor (TNF) Antagonists No | 15 Participants | 35 Participants | 50 Participants |
| Prior Exposure to Tumor Necrosis Factor (TNF) Antagonists Yes | 6 Participants | 12 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 12 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 30 Participants | 41 Participants |
| Sex: Female, Male Female | 16 Participants | 37 Participants | 53 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 47 | 0 / 19 | 0 / 41 |
| other Total, other adverse events | 6 / 21 | 12 / 47 | 10 / 19 | 12 / 41 |
| serious Total, serious adverse events | 0 / 21 | 3 / 47 | 0 / 19 | 5 / 41 |
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 total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline.
Time frame: Baseline and Week 12
Population: Intent-to-treat population; participants with missing data at Week 12 due to a missing assessment or early discontinuation, for reasons other than coronavirus disease 2019 (COVID-19), and participants who initiated antibiotics for HS-related infections prior to Week 12 were counted as non-responders (non-responder imputation); missing data due to COVID-19 infection or logistical restriction were handled by multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | 23.8 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 | 38.3 percentage of participants |
Comparison: The primary analysis compared the percentage of participants in the upadacitinib 30 mg treatment group who achieved HiSCR response to that of a prespecified, single historical placebo rate (25%). The historical placebo rate of 25% was assumed based on the corresponding response rates of placebo participants satisfying the same key eligibility criteria from the 2 adalimumab HS Phase 3 studies, Study M11-313 (NCT01468207) and Study M11-810 (NCT01468233).p-value: 0.01895% CI: [-0.6, 27.2]Chi-squared
Comparison: As a supplemental analysis, the percentage of participants who achieved HiSCR at Week 12 was further analyzed by comparing upadacitinib with in-trial placebo participants combined with subjects with historical placebo HiSCR data pre-selected using propensity score matching from adalimumab studies M11-313 and M11-810 and risankizumab study M16-833 (NCT03926169), whose study populations, entry criteria and study designs were similar to this study. The placebo in-trial + synthetic HiSCR was 29.2%.p-value: 0.14295% CI: [-7.6, 25.9]Cochran-Mantel-Haenszel
Comparison: As an additional supplemental analysis, the percentage of participants who achieved HiSCR at Week 12 was also analyzed by comparing upadacitinib 30 mg with in-trial placebo participants.p-value: 0.08795% CI: [-6.6, 36]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving PGA Skin Pain Numeric Rating Scale 30 (NRS30) Response at Week 12 Among Participants With Baseline NRS ≥ 3
The Patient's Global Assessment (PGA) of Skin Pain Numeric Rating Scale (NRS) was used to assess the worst skin pain due to HS. Participants were asked to rate their worst skin pain in the last 24 hours on an 11-point numerical rating scale ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine) on a daily basis using an electronic diary. The weekly average score was calculated based on the daily scores from the 7 days prior to the visit (with non-missing values in 4 or more days of the 7 day period). NRS30 is defined as the percentage of participants who achieved at least a 30% reduction and at least 1 unit reduction from Baseline in the PGA of skin pain NRS in participants with Baseline skin pain NRS ≥ 3.
Time frame: Baseline and Week 12
Population: Intent-to-treat population with Baseline skin pain NRS ≥ 3; participants with missing data at Week 12 due to a missing assessment or early discontinuation, for reasons other than COVID-19, and participants who initiated antibiotics for HS-related infections prior to Week 12 and under the impact of analgesic use at Week 12 were counted as non-responders (non-responder imputation); missing data due to COVID-19 infection or logistical restriction were handled by multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving PGA Skin Pain Numeric Rating Scale 30 (NRS30) Response at Week 12 Among Participants With Baseline NRS ≥ 3 | 33.3 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Achieving PGA Skin Pain Numeric Rating Scale 30 (NRS30) Response at Week 12 Among Participants With Baseline NRS ≥ 3 | 36.4 percentage of participants |
Comparison: The primary analysis compared the percentage of participants in the upadacitinib 30 mg treatment group who achieved NRS30 response to that of a prespecified, single historical placebo rate (22.5%). The historical placebo rate of 22.5% was assumed based on the corresponding response rates of placebo participants satisfying the same key eligibility criteria from the 2 adalimumab HS Phase 3 studies, Study M11-313 (NCT01468207) and Study M11-810 (NCT01468233).p-value: 0.02895% CI: [-2.5, 30.3]Chi-squared
Comparison: As a supplemental analysis, the percentage of participants who achieved NRS30 at Week 12 was further analyzed by comparing upadacitinib with in-trial placebo participants combined with subjects with historical placebo NRS30 data pre-selected using propensity score matching from adalimumab studies M11-313 and M11-810 and risankizumab study M16-833 (NCT03926169), whose study populations, entry criteria and study designs were similar to this study. The placebo in-trial + synthetic NRS30 was 31.3%.p-value: 0.32395% CI: [-14.6, 23.5]Cochran-Mantel-Haenszel
Comparison: As an additional supplemental analysis, the percentage of participants who achieved NRS30 at Week 12 was also analyzed by comparing upadacitinib 30 mg with in-trial placebo participants.p-value: 0.42195% CI: [-19.6, 24]Cochran-Mantel-Haenszel