Hidradenitis Suppurativa
Conditions
Keywords
IL-36 receptor, Interleukin 36, Imsidolimab
Brief summary
Efficacy and safety of imsidolimab (ANB019) in participants with Hidradenitis Suppurativa
Detailed description
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of imsidolimab in adult participants with hidradenitis suppurativa (HS). This study will also characterize the pharmacokinetic (PK) profile of imsidolimab and explore the immune response to imsidolimab in participants with HS.
Interventions
BIOLOGICALImsidolimab
Humanized Monoclonal Antibody
BIOLOGICALPlacebo
Placebo
Sponsors
Vanda Pharmaceuticals
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 75 Years
Healthy volunteers
No
Inclusion criteria
1. Clinically confirmed diagnosis of active HS with a disease duration of greater than or equal to (≥) 6 months before Day 1. 2. HS lesions present in at least 2 distinct anatomical areas. 3. Total Abscess and inflammatory nodule (AN) count ≥ 5. 4. Draining fistulas less than or equal to (≤) 20. 5. Stable HS for at least 6 weeks prior to Day 1 visit.
Exclusion criteria
1\. Concomitant dermatological or medical conditions that may interfere with the Investigators' ability to evaluate the participant's response to therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | Baseline, Week 16 | The AN count was defined as the sum of the number of abscesses and inflammatory nodules from all locations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50): Placebo-Controlled Period | Week 16 | The number of participants with at least a 50% decrease from Baseline AN count, and no increase in abscesses or draining fistulas in comparison to baseline (HiSCR50) at Week 16 was calculated for each treatment group as follows: A responder HiSCR50 was defined as a participant with 1. at least a 50% decrease in AN count from Baseline, and 2. no increase in abscess count relative to Baseline, and 3. no increase in draining fistula count relative to Baseline |
| Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | Baseline, Week 16 | Participants were asked to assign a numerical score representing the HS worst pain intensity over the last 24 hours on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms). |
| Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | Baseline, Week 16 | Participants were asked to assign a numerical score representing the average intensity over the last 7 days of their HS pain symptoms on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms). |
| Percent Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | Baseline, Week 16 | The AN count was defined as the sum of the number of abscesses and inflammatory nodules from all locations. |
| Percent Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | Baseline, Week 16 | Participants were asked to assign a numerical score representing the average intensity over the last 7 days of their HS pain symptoms on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms). Only participants that had Baseline score of \>0 could be included in the analysis of Percent Change from Baseline. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs): Placebo-Controlled Period | From first dose (placebo-controlled period) up to Week 16 | An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment during placebo-controlled period, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment. |
| Number of Participants With TEAEs: Extension and Follow-up Period | From first dose (extension period) up to Week 40 | An AE was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment in extension period, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment. |
| Percent Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | Baseline, Week 16 | Participants were asked to assign a numerical score representing the HS worst pain intensity over the last 24 hours on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms). Only participants that had Baseline score of \>0 could be included in the analysis of Percent Change from Baseline. |
Countries
Canada, Georgia, Poland, United States
Participant flow
Recruitment details
Participants who had a clinically confirmed diagnosis of hidradenitis suppurativa (HS) with a disease duration of at least 6 months before Day 1, were enrolled in the study. Randomization was stratified based on Hurley Stage at Baseline (Stage II or III).
Pre-assignment details
227 participants were screened for eligibility and 149 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Imsidolimab 400/200 mg Placebo-controlled period: Participants received a starting dose of 400 milligrams (mg) of imsidolimab on Day 1 followed by 200 mg imsidolimab every 4 weeks (Days 29, 57 and 85) by subcutaneous (SC) injection. The placebo-controlled period ended at Day 113 (Week 16).
Extension period: Participants received imsidolimab at the same dose as placebo-controlled period, SC every 4 weeks (Days 113, 141, 169, and 197).
After discontinuation from treatment, participants remained in the study for safety follow-up period of 8 weeks. | 50 |
| Imsidolimab 200/100 mg Placebo-controlled period: Participants received a starting dose of 200 mg of imsidolimab on Day 1 followed by 100 mg imsidolimab every 4 weeks (Days 29, 57 and 85) by SC injection. The placebo-controlled period ended at Day 113 (Week 16).
Extension period: Participants received imsidolimab at the same dose as placebo-controlled period, SC every 4 weeks (Days 113, 141, 169, and 197).
After discontinuation from treatment, participants remained in the study for safety follow-up period of 8 weeks. | 50 |
| Placebo Placebo-controlled period: Participants received imsidolimab matching placebo on Day 1 and thereafter, every 4 weeks (Days 29, 57 and 85) by SC injection. The placebo-controlled period ended at Day 113 (Week 16).
Extension period: Participants received imsidolimab at the same dose as placebo-controlled period, SC every 4 weeks (Days 113, 141, 169, and 197).
After discontinuation from treatment, participants remained in the study for safety follow-up period of 8 weeks. | 49 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Extension Period (16 Weeks) | Adverse Event | 1 | 0 | 1 |
| Extension Period (16 Weeks) | Lost to Follow-up | 2 | 5 | 1 |
| Extension Period (16 Weeks) | Other than specified | 0 | 0 | 1 |
| Extension Period (16 Weeks) | Pregnancy | 0 | 0 | 2 |
| Extension Period (16 Weeks) | Stopped participation by Sponsor | 0 | 0 | 2 |
| Extension Period (16 Weeks) | Use of Any Prohibited Medication or Treatment | 1 | 0 | 0 |
| Extension Period (16 Weeks) | Withdrawal by Subject | 9 | 5 | 1 |
| Follow-up Period (8 Weeks) | Adverse Event | 0 | 0 | 1 |
| Follow-up Period (8 Weeks) | Lost to Follow-up | 0 | 0 | 1 |
| Follow-up Period (8 Weeks) | Stopped participation by Sponsor | 12 | 12 | 17 |
| Follow-up Period (8 Weeks) | Withdrawal by Subject | 3 | 2 | 3 |
| Placebo-controlled Period (16 Weeks) | Adverse Event | 0 | 0 | 1 |
| Placebo-controlled Period (16 Weeks) | Lost to Follow-up | 3 | 1 | 0 |
| Placebo-controlled Period (16 Weeks) | Pregnancy | 0 | 1 | 0 |
| Placebo-controlled Period (16 Weeks) | Protocol Violation | 0 | 0 | 1 |
| Placebo-controlled Period (16 Weeks) | Use of Any Prohibited Medication or Treatment | 0 | 1 | 0 |
| Placebo-controlled Period (16 Weeks) | Withdrawal by Subject | 6 | 5 | 4 |
Baseline characteristics
| Characteristic | Imsidolimab 400/200 mg | Total | Placebo | Imsidolimab 200/100 mg |
|---|---|---|---|---|
| Abscess and Inflammatory Nodule (AN) Count | 14.0 count of abscess and inflammatory nodule STANDARD_DEVIATION 9.87 | 12.7 count of abscess and inflammatory nodule STANDARD_DEVIATION 9.34 | 12.1 count of abscess and inflammatory nodule STANDARD_DEVIATION 8.31 | 11.9 count of abscess and inflammatory nodule STANDARD_DEVIATION 9.79 |
| Age, Continuous | 34.2 years STANDARD_DEVIATION 11.35 | 35.7 years STANDARD_DEVIATION 11.68 | 36.8 years STANDARD_DEVIATION 11.56 | 36.0 years STANDARD_DEVIATION 12.2 |
| Average pain NRS Score | 5.7 units on a scale STANDARD_DEVIATION 2.61 | 5.8 units on a scale STANDARD_DEVIATION 2.63 | 5.7 units on a scale STANDARD_DEVIATION 2.6 | 6.0 units on a scale STANDARD_DEVIATION 2.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 22 Participants | 6 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 127 Participants | 43 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hurley Stage Hurley Stage IIl | 14 Participants | 38 Participants | 12 Participants | 12 Participants |
| Hurley Stage Hurley Stage Il | 36 Participants | 111 Participants | 37 Participants | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 29 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 110 Participants | 37 Participants | 37 Participants |
| Region of Enrollment Canada | 5 participants | 15 participants | 6 participants | 4 participants |
| Region of Enrollment Georgia | 5 participants | 7 participants | 0 participants | 2 participants |
| Region of Enrollment Poland | 11 participants | 39 participants | 13 participants | 15 participants |
| Region of Enrollment United States | 29 participants | 88 participants | 30 participants | 29 participants |
| Sex: Female, Male Female | 31 Participants | 96 Participants | 28 Participants | 37 Participants |
| Sex: Female, Male Male | 19 Participants | 53 Participants | 21 Participants | 13 Participants |
| Worst Pain Numeric Rating Scale (NRS) Score | 5.3 units on a scale STANDARD_DEVIATION 2.54 | 5.4 units on a scale STANDARD_DEVIATION 2.7 | 5.6 units on a scale STANDARD_DEVIATION 2.79 | 5.4 units on a scale STANDARD_DEVIATION 2.81 |
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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 49 | 0 / 40 | 0 / 42 | 0 / 19 | 0 / 21 |
| other Total, other adverse events | 5 / 50 | 6 / 50 | 9 / 49 | 9 / 40 | 10 / 42 | 9 / 19 | 5 / 21 |
| serious Total, serious adverse events | 0 / 50 | 2 / 50 | 3 / 49 | 0 / 40 | 1 / 42 | 0 / 19 | 0 / 21 |
Outcome results
Primary
Change From Baseline in AN Count at Week 16: Placebo-Controlled Period
The AN count was defined as the sum of the number of abscesses and inflammatory nodules from all locations.
Time frame: Baseline, Week 16
Population: ITT Analysis Set with available data was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | -5.9 count of abscess and inflammatory nodule | Standard Deviation 6.05 |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | -4.1 count of abscess and inflammatory nodule | Standard Deviation 4.63 |
| Placebo-Controlled Period: Placebo | Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | -5.6 count of abscess and inflammatory nodule | Standard Deviation 7.4 |
p-value: 0.784190% CI: [-2.42, 1.73]Linear repeated measures model (LRMM)
p-value: 0.288590% CI: [-0.74, 3.4]LRMM
Secondary
Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period
Participants were asked to assign a numerical score representing the average intensity over the last 7 days of their HS pain symptoms on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms).
Time frame: Baseline, Week 16
Population: ITT Analysis Set with available data was analyzed; change and percent change in worst HS pain NRS and change and percent change in average HS pain NRS are 2 different CRF questions, and so the number of responses can (and do) differ between the questions at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | -0.5 units on a scale | Standard Deviation 2.29 |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | -1.0 units on a scale | Standard Deviation 2.48 |
| Placebo-Controlled Period: Placebo | Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | -0.5 units on a scale | Standard Deviation 2.74 |
p-value: 0.769890% CI: [-0.96, 0.67]LRMM
p-value: 0.746890% CI: [-0.97, 0.65]LRMM
Secondary
Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period
Participants were asked to assign a numerical score representing the HS worst pain intensity over the last 24 hours on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms).
Time frame: Baseline, Week 16
Population: ITT Analysis Set with available data was analyzed; change and percent change in worst HS pain NRS and change and percent change in average HS pain NRS are 2 different CRF questions, and so the number of responses can (and do) differ between the questions at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | -0.3 units on a scale | Standard Deviation 2.89 |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | -0.7 units on a scale | Standard Deviation 2.37 |
| Placebo-Controlled Period: Placebo | Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | -0.4 units on a scale | Standard Deviation 3.22 |
p-value: 0.728290% CI: [-1.08, 0.7]LRMM
p-value: 0.501990% CI: [-1.25, 0.53]LRMM
Secondary
Number of Participants Achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50): Placebo-Controlled Period
The number of participants with at least a 50% decrease from Baseline AN count, and no increase in abscesses or draining fistulas in comparison to baseline (HiSCR50) at Week 16 was calculated for each treatment group as follows: A responder HiSCR50 was defined as a participant with 1. at least a 50% decrease in AN count from Baseline, and 2. no increase in abscess count relative to Baseline, and 3. no increase in draining fistula count relative to Baseline
Time frame: Week 16
Population: ITT Analysis Set with available data was analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Number of Participants Achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50): Placebo-Controlled Period | 16 Participants |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Number of Participants Achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50): Placebo-Controlled Period | 16 Participants |
| Placebo-Controlled Period: Placebo | Number of Participants Achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR50): Placebo-Controlled Period | 15 Participants |
90% CI: [-13.3, 23.4]
90% CI: [-14.6, 21]
Secondary
Number of Participants With TEAEs: Extension and Follow-up Period
An AE was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment in extension period, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment.
Time frame: From first dose (extension period) up to Week 40
Population: Extension Analysis Set included subset of the safety analysis set who received at least 1 dose of imsidolimab in the extension period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Number of Participants With TEAEs: Extension and Follow-up Period | 15 Participants |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Number of Participants With TEAEs: Extension and Follow-up Period | 18 Participants |
| Placebo-Controlled Period: Placebo | Number of Participants With TEAEs: Extension and Follow-up Period | 9 Participants |
| Extension Period: Placebo to Imsidolimab 200/100 mg | Number of Participants With TEAEs: Extension and Follow-up Period | 10 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs): Placebo-Controlled Period
An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE was considered treatment-emergent if the date of onset was during or after first dose of study treatment during placebo-controlled period, or if the AE present at baseline worsened in either intensity or frequency after first dose of study treatment.
Time frame: From first dose (placebo-controlled period) up to Week 16
Population: Safety analysis set included all randomized participants who received at least 1 dose of imsidolimab or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Placebo-Controlled Period | 19 Participants |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Placebo-Controlled Period | 14 Participants |
| Placebo-Controlled Period: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs): Placebo-Controlled Period | 18 Participants |
Secondary
Percent Change From Baseline in AN Count at Week 16: Placebo-Controlled Period
The AN count was defined as the sum of the number of abscesses and inflammatory nodules from all locations.
Time frame: Baseline, Week 16
Population: ITT Analysis Set with available data was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Percent Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | -44.7 percent change | Standard Deviation 39.23 |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Percent Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | -36.7 percent change | Standard Deviation 36.59 |
| Placebo-Controlled Period: Placebo | Percent Change From Baseline in AN Count at Week 16: Placebo-Controlled Period | -41.2 percent change | Standard Deviation 43.69 |
p-value: 0.593990% CI: [-19.66, 10.07]LRMM
p-value: 0.700290% CI: [-11.38, 18.29]LRMM
Secondary
Percent Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period
Participants were asked to assign a numerical score representing the average intensity over the last 7 days of their HS pain symptoms on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms). Only participants that had Baseline score of \>0 could be included in the analysis of Percent Change from Baseline.
Time frame: Baseline, Week 16
Population: ITT Analysis Set with available data was analyzed; change and percent change in worst HS pain NRS and change and percent change in average HS pain NRS are 2 different CRF questions, and so the number of responses can (and do) differ between the questions at baseline. Overall number of participants analyzed included only those participants with Baseline score of \>0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Percent Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | -1.3 percent change | Standard Deviation 58.54 |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Percent Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | -18.3 percent change | Standard Deviation 37.76 |
| Placebo-Controlled Period: Placebo | Percent Change From Baseline in Average HS Pain NRS Score at Week 16: Placebo-Controlled Period | 4.5 percent change | Standard Deviation 77.25 |
p-value: 0.614690% CI: [-28.22, 15.05]LRMM
p-value: 0.495190% CI: [-30.35, 12.62]LRMM
Secondary
Percent Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period
Participants were asked to assign a numerical score representing the HS worst pain intensity over the last 24 hours on a scale from 0 (no symptoms) to 10 (worst imaginable symptoms). Only participants that had Baseline score of \>0 could be included in the analysis of Percent Change from Baseline.
Time frame: Baseline, Week 16
Population: ITT Analysis Set with available data was analyzed; change and percent change in worst HS pain NRS and change and percent change in average HS pain NRS are 2 different CRF questions, and so the number of responses can (and do) differ between the questions at baseline. Overall number of participants analyzed included only those participants with Baseline score of \>0.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Period: Imsidolimab 400/200 mg | Percent Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | 7.6 percent change | Standard Deviation 81.81 |
| Placebo-Controlled Period: Imsidolimab 200/100 mg | Percent Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | 10.2 percent change | Standard Deviation 146.92 |
| Placebo-Controlled Period: Placebo | Percent Change From Baseline in Worst HS Pain NRS Score at Week 16: Placebo-Controlled Period | 30.3 percent change | Standard Deviation 136.89 |
p-value: 0.27590% CI: [-64.57, 13.14]LRMM
p-value: 0.375790% CI: [-60.6, 18.28]LRMM