Hidradenitis Suppurativa
Conditions
Keywords
Hidradenitis Suppurativa, Risankizumab, Placebo
Brief summary
The primary objective of this study is to assess the safety and efficacy of risankizumab 180 mg and 360 mg versus placebo for the treatment of signs and symptoms of moderate to severe hidradenitis suppurativa (HS) in adult participants diagnosed for at least one year before the Baseline visit.
Interventions
DRUGRisankizumab
Risankizumab is administered as a SC injection in pre-filled syringe (PFS)
Placebo for risankizumab is administered as a SC injection in PFS
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
* Participant with moderate to severe HS for at least 1 year prior to baseline visit. * HS lesions present in at least two distinct anatomical areas. * Draining fistula count of ≤ 20 at Baseline visit. * Total abscess and inflammatory nodule (AN) count of ≥ 5 at Baseline visit. * Participants are required to use a daily antiseptic wash on their HS lesions. * Participant must have a history of inadequate response or intolerance to an adequate trial of oral antibiotics for treatment of HS.
Exclusion criteria
* Participant has a history of active skin disease other than HS that could interfere with the assessment of HS. * Participant has active tuberculosis (TB) or concurrent treatment for latent TB or evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection. * Participant has prior exposure to anti-interleukin-1 (anti-IL-1) treatment within 3 months or 5 half-lives, whichever is longer, prior to baseline. * Participant has received prescription topical therapies (including topical antibiotics) within 14 days prior to the Baseline visit. * Participant has received systemic non-biologic therapies that can also be used to treat HS within 4 weeks prior to the Baseline visit. * Participant has received any systemic (including oral) antibiotic treatment within 4 weeks prior to the Baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | Baseline (Week 0), Week 16 | HiSCR is defined as at least a 50% reduction from Baseline in the total abscess and inflammatory nodule (AN) count, with no increase in abscess or draining fistula counts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in PGA of Skin Pain Numerical Rating Scale (NRS30) at Week 16 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | Baseline (Week 0) to Week 16 | NRS30 is evaluated based on worst skin pain in a 24-hour recall period (maximal daily pain), ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline at Week 16 in the PGA of Skin Pain (NRS30) - at worst, among participants with Baseline NRS ≥ 3, is presented. |
| Percentage of Participants Who Experienced ≥ 25% Increase in Abscess and Inflammatory Nodule (AN) Counts in Period A With a Minimum Increase of 2 Relative to Baseline | Baseline (Week 0) to Week 16 | — |
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | Baseline (Week 0) to Week 16 | The DLQI is a 10-item validated questionnaire used to assess the impact of HS disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. DLQI scores range from 0 to 30, with a higher score indicating a more impaired QoL. |
| Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in Patient's Global Assessment (PGA) of Skin Pain Numerical Rating Scale (NRS30) at Week 8 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | Baseline (Week 0) to Week 8 | NRS30 is evaluated based on worst skin pain in a 24-hour recall period (maximal daily pain), ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline at Week 8 in the PGA of Skin Pain (NRS30) - at worst, among participants with Baseline NRS ≥ 3, is presented. |
| Change From Baseline in HS-Related Odor Based on the HSSA Bad Smell Score at Week 16 | Baseline (Week 0) to Week 16 | HSSA is a 9-item PRO questionnaire developed to assess the symptoms of HS. HS-related odor is scored on an 11-point NRS, where 0 represents no symptoms and 10 represents extreme symptom experience. |
| Change From Baseline in HS-Related Worst Drainage Based on the HSSA Worst Drainage Score at Week 16 | Baseline (Week 0) to Week 16 | HSSA is a 9-item PRO questionnaire developed to assess the symptoms of HS. HS-related worst drainage is scored on an 11-point NRS, where 0 represents no symptoms and 10 represents extreme symptom experience. |
| Change From Baseline in HS-Related Swelling Based on the Hidradenitis Suppurativa Symptom Assessment (HSSA) Swollen Skin Score at Week 16 | Baseline (Week 0) to Week 16 | HSSA is a 9-item participant-reported outcome (PRO) questionnaire developed to assess the symptoms of HS. HS-related swelling is scored on an 11-point NRS, where 0 represents no symptoms and 10 represents extreme symptom experience. |
Countries
Australia, Canada, France, Germany, Japan, Netherlands, Spain, United States
Participant flow
Pre-assignment details
In Period A, participants who met the study's eligibility criteria were randomized at the Baseline Visit, in a 1:1:1 ratio, to receive either placebo, risankizumab 180 mg or 360 mg via a subcutaneous (SC) injection.
Participants by arm
| Arm | Count |
|---|---|
| Placebo / Risankizumab 360 mg In Period A, participants received blinded placebo via SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12.
In Period B, participants received blinded risankizumab 360 mg at Weeks 16, 17, and 18. Starting at Week 20, participants received open-label risankizumab 360 mg every 8 weeks (q8w) at Weeks 20, 28, 36, 44, 52, and 60. | 82 |
| Risankizumab 180 mg / Risankizumab 360 mg In Period A, participants received blinded risankizumab 180 mg via SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12.
In Period B, participants received blinded placebo at Weeks 16, 17, and 18. Starting at Week 20, participants received open-label risankizumab 360 mg q8w at Weeks 20, 28, 36, 44, 52, and 60. | 80 |
| Risankizumab 360 mg / Risankizumab 360 mg In Period A, participants received blinded risankizumab 360 mg via SC injection at Weeks 0 (Baseline), 1, 2, 4, and 12.
In Period B, participants received blinded placebo at Weeks 16, 17, and 18. Starting at Week 20, participants received open-label risankizumab 360 mg q8w at Weeks 20, 28, 36, 44, 52, and 60. | 81 |
| Total | 243 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period A | Adverse Event | 2 | 2 | 1 |
| Period A | COVID-19 Infection | 0 | 1 | 0 |
| Period A | COVID-19 Logistical Restrictions | 0 | 2 | 1 |
| Period A | Lack of Efficacy | 0 | 2 | 2 |
| Period A | Lost to Follow-up | 3 | 1 | 0 |
| Period A | Other, Not Specified | 1 | 0 | 0 |
| Period A | Withdrawal by Subject | 2 | 2 | 2 |
| Period B | Adverse Event | 3 | 1 | 1 |
| Period B | Lack of Efficacy | 3 | 1 | 1 |
| Period B | Lost to Follow-up | 1 | 1 | 4 |
| Period B | Other, Not Specified | 62 | 57 | 65 |
| Period B | Withdrawal by Subject | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo / Risankizumab 360 mg | Risankizumab 180 mg / Risankizumab 360 mg | Risankizumab 360 mg / Risankizumab 360 mg |
|---|---|---|---|---|
| Abscess and Inflammatory Nodule (AN) Count | 14.0 abscess and inflammatory nodules STANDARD_DEVIATION 18.36 | 15.7 abscess and inflammatory nodules STANDARD_DEVIATION 28.42 | 13.7 abscess and inflammatory nodules STANDARD_DEVIATION 11.42 | 12.5 abscess and inflammatory nodules STANDARD_DEVIATION 8.24 |
| Age, Continuous | 38.1 years STANDARD_DEVIATION 11.77 | 37.2 years STANDARD_DEVIATION 11.97 | 38.9 years STANDARD_DEVIATION 11.45 | 38.2 years STANDARD_DEVIATION 11.99 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants | 8 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 25 Participants | 4 Participants | 12 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 26 Participants | 9 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized Multiple Races | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 217 Participants | 73 Participants | 70 Participants | 74 Participants |
| Race/Ethnicity, Customized White | 193 Participants | 68 Participants | 63 Participants | 62 Participants |
| Sex: Female, Male Female | 152 Participants | 48 Participants | 53 Participants | 51 Participants |
| Sex: Female, Male Male | 91 Participants | 34 Participants | 27 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 80 | 0 / 80 | 0 / 74 | 0 / 70 | 0 / 74 |
| other Total, other adverse events | 19 / 82 | 21 / 80 | 26 / 80 | 26 / 74 | 12 / 70 | 19 / 74 |
| serious Total, serious adverse events | 2 / 82 | 3 / 80 | 2 / 80 | 3 / 74 | 4 / 70 | 0 / 74 |
Outcome results
Primary
Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16
HiSCR is defined as at least a 50% reduction from Baseline in the total abscess and inflammatory nodule (AN) count, with no increase in abscess or draining fistula counts.
Time frame: Baseline (Week 0), Week 16
Population: Intent-to-Treat Population: all randomized participants. Non-responder imputation with multiple imputation to handle missing data due to COVID-19 (NRI-C) .
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | 41.5 percentage of participants |
| Risankizumab 180 mg | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | 46.8 percentage of participants |
| Risankizumab 360 mg | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16 | 43.4 percentage of participants |
p-value: 0.42297.5% CI: [-10.8, 22.8]Cochran-Mantel-Haenszel
p-value: 0.85897.5% CI: [-15.4, 18.1]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16
The DLQI is a 10-item validated questionnaire used to assess the impact of HS disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. DLQI scores range from 0 to 30, with a higher score indicating a more impaired QoL.
Time frame: Baseline (Week 0) to Week 16
Population: Intent-to-Treat Population: all randomized participants. Participants with an assessment at given time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -2.1 score on a scale |
| Risankizumab 180 mg | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -3.5 score on a scale |
| Risankizumab 360 mg | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -3.7 score on a scale |
p-value: 0.17997.5% CI: [-3.5, 0.9]mixed-effect model repeat measures
p-value: 0.10597.5% CI: [-3.8, 0.6]mixed-effect model repeat measures
Secondary
Change From Baseline in HS-Related Odor Based on the HSSA Bad Smell Score at Week 16
HSSA is a 9-item PRO questionnaire developed to assess the symptoms of HS. HS-related odor is scored on an 11-point NRS, where 0 represents no symptoms and 10 represents extreme symptom experience.
Time frame: Baseline (Week 0) to Week 16
Population: Intent-to-Treat Population: all randomized participants. Participants with an assessment at given time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in HS-Related Odor Based on the HSSA Bad Smell Score at Week 16 | -0.677 score on a scale |
| Risankizumab 180 mg | Change From Baseline in HS-Related Odor Based on the HSSA Bad Smell Score at Week 16 | -0.635 score on a scale |
| Risankizumab 360 mg | Change From Baseline in HS-Related Odor Based on the HSSA Bad Smell Score at Week 16 | -0.442 score on a scale |
p-value: 0.88697.5% CI: [-0.622, 0.706]mixed-effect model repeat measures
p-value: 0.40997.5% CI: [-0.408, 0.879]mixed-effect model repeat measures
Secondary
Change From Baseline in HS-Related Swelling Based on the Hidradenitis Suppurativa Symptom Assessment (HSSA) Swollen Skin Score at Week 16
HSSA is a 9-item participant-reported outcome (PRO) questionnaire developed to assess the symptoms of HS. HS-related swelling is scored on an 11-point NRS, where 0 represents no symptoms and 10 represents extreme symptom experience.
Time frame: Baseline (Week 0) to Week 16
Population: Intent-to-Treat Population: all randomized participants. Participants with an assessment at given time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in HS-Related Swelling Based on the Hidradenitis Suppurativa Symptom Assessment (HSSA) Swollen Skin Score at Week 16 | -0.870 score on a scale |
| Risankizumab 180 mg | Change From Baseline in HS-Related Swelling Based on the Hidradenitis Suppurativa Symptom Assessment (HSSA) Swollen Skin Score at Week 16 | -0.751 score on a scale |
| Risankizumab 360 mg | Change From Baseline in HS-Related Swelling Based on the Hidradenitis Suppurativa Symptom Assessment (HSSA) Swollen Skin Score at Week 16 | -0.885 score on a scale |
p-value: 0.72797.5% CI: [-0.646, 0.883]mixed-effect model repeat measures
p-value: 0.96397.5% CI: [-0.755, 0.724]mixed-effect model repeat measures
Secondary
Change From Baseline in HS-Related Worst Drainage Based on the HSSA Worst Drainage Score at Week 16
HSSA is a 9-item PRO questionnaire developed to assess the symptoms of HS. HS-related worst drainage is scored on an 11-point NRS, where 0 represents no symptoms and 10 represents extreme symptom experience.
Time frame: Baseline (Week 0) to Week 16
Population: Intent-to-Treat Population: all randomized participants. Participants with an assessment at given time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in HS-Related Worst Drainage Based on the HSSA Worst Drainage Score at Week 16 | -0.630 score on a scale |
| Risankizumab 180 mg | Change From Baseline in HS-Related Worst Drainage Based on the HSSA Worst Drainage Score at Week 16 | -0.882 score on a scale |
| Risankizumab 360 mg | Change From Baseline in HS-Related Worst Drainage Based on the HSSA Worst Drainage Score at Week 16 | -0.705 score on a scale |
p-value: 0.43497.5% CI: [-0.977, 0.473]mixed-effect model repeat measures
p-value: 0.81397.5% CI: [-0.779, 0.631]mixed-effect model repeat measures
Secondary
Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in Patient's Global Assessment (PGA) of Skin Pain Numerical Rating Scale (NRS30) at Week 8 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3
NRS30 is evaluated based on worst skin pain in a 24-hour recall period (maximal daily pain), ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline at Week 8 in the PGA of Skin Pain (NRS30) - at worst, among participants with Baseline NRS ≥ 3, is presented.
Time frame: Baseline (Week 0) to Week 8
Population: Intent-to-Treat Population: all randomized participants. Participants with Baseline NRS ≥ 3. Non-responder imputation with multiple imputation to handle missing data due to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in Patient's Global Assessment (PGA) of Skin Pain Numerical Rating Scale (NRS30) at Week 8 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | 33.0 percentage of participants |
| Risankizumab 180 mg | Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in Patient's Global Assessment (PGA) of Skin Pain Numerical Rating Scale (NRS30) at Week 8 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | 29.2 percentage of participants |
| Risankizumab 360 mg | Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in Patient's Global Assessment (PGA) of Skin Pain Numerical Rating Scale (NRS30) at Week 8 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | 40.0 percentage of participants |
p-value: 0.72597.5% CI: [-21.8, 15.9]Cochran-Mantel-Haenszel
p-value: 0.30197.5% CI: [-10.3, 27.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in PGA of Skin Pain Numerical Rating Scale (NRS30) at Week 16 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3
NRS30 is evaluated based on worst skin pain in a 24-hour recall period (maximal daily pain), ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline at Week 16 in the PGA of Skin Pain (NRS30) - at worst, among participants with Baseline NRS ≥ 3, is presented.
Time frame: Baseline (Week 0) to Week 16
Population: Intent-to-Treat Population: all randomized participants. Participants with Baseline NRS ≥ 3. Non-responder imputation with multiple imputation to handle missing data due to COVID-19.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in PGA of Skin Pain Numerical Rating Scale (NRS30) at Week 16 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | 27.9 percentage of participants |
| Risankizumab 180 mg | Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in PGA of Skin Pain Numerical Rating Scale (NRS30) at Week 16 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | 31.1 percentage of participants |
| Risankizumab 360 mg | Percentage of Participants Achieving ≥ 30% Reduction and ≥ 1 Unit Reduction From Baseline in PGA of Skin Pain Numerical Rating Scale (NRS30) at Week 16 Among Participants With Baseline Numerical Rating Scale (NRS) ≥ 3 | 38.6 percentage of participants |
p-value: 0.6597.5% CI: [-14.5, 21.8]Cochran-Mantel-Haenszel
p-value: 0.14797.5% CI: [-6.7, 31.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Experienced ≥ 25% Increase in Abscess and Inflammatory Nodule (AN) Counts in Period A With a Minimum Increase of 2 Relative to Baseline
Time frame: Baseline (Week 0) to Week 16
Population: Intent-to-Treat Population: all randomized participants. Participants with Baseline NRS ≥ 3. Non-responder imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Experienced ≥ 25% Increase in Abscess and Inflammatory Nodule (AN) Counts in Period A With a Minimum Increase of 2 Relative to Baseline | 29.3 percentage of participants |
| Risankizumab 180 mg | Percentage of Participants Who Experienced ≥ 25% Increase in Abscess and Inflammatory Nodule (AN) Counts in Period A With a Minimum Increase of 2 Relative to Baseline | 22.5 percentage of participants |
| Risankizumab 360 mg | Percentage of Participants Who Experienced ≥ 25% Increase in Abscess and Inflammatory Nodule (AN) Counts in Period A With a Minimum Increase of 2 Relative to Baseline | 18.5 percentage of participants |
p-value: 0.34297.5% CI: [-21.8, 8.8]Cochran-Mantel-Haenszel
p-value: 0.10897.5% CI: [-25.3, 4.2]Cochran-Mantel-Haenszel