Hidradenitis Suppurativa
Conditions
Keywords
hidradenitis suppurativa, Izokibep
Brief summary
Izokibep is a potent and selective inhibitor of interleukin 17A (IL-17A) that is being developed for treatment of hidradenitis suppurativa (HS). This study will evaluate the efficacy, safety, and immunogenicity of izokibep administered subcutaneously (SC) in adult subjects with moderate to severe HS.
Interventions
DRUGIzokibep
Biologic: IL-17A inhibitor Form: Solution for injection Route of administration: Subcutaneous (SC)
Form: Solution for injection Route of administration: Subcutaneous (SC)
Sponsors
ACELYRIN Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
General * Subject has provided signed informed consent including consenting to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * 18 years to 75 years of age Type of Subject and Disease Characteristics * Diagnosis of hidradenitis suppurativa (HS) for ≥ 1 year prior to first dose of study drug. * Hidradenitis suppurativa lesions present in ≥ 2 distinct anatomic areas, one of which is Hurley Stage II or III. * A total abscess and inflammatory nodule (AN) count of ≥ 5 at screening and Day 1 prior to enrollment/randomization. * Subject must have had an inadequate response to oral antibiotics OR exhibited recurrence after discontinuation to, OR demonstrated intolerance to, OR have a contraindication to oral antibiotics for treatment of their HS. * Must agree to use daily over-the-counter topical antiseptics. * Subject must be willing to complete a daily skin pain diary for at least 3 days prior to Day 1 visit.
Exclusion criteria
Medical Conditions * Draining fistula count of \> 20. * Outpatient surgery ≤ 8 weeks prior or inpatient surgery ≤ 12 weeks prior to enrollment/randomization. * Other active skin disease or condition that could interfere with study assessments. * Chronic pain not associated with HS. * Uncontrolled, clinically significant system disease. * History of demyelinating disease or neurological symptoms suggestive of demyelinating disease. * Malignancy within 5 years. * The subject is at risk of self-harm or harm to others. * Active infection or history of certain infections. * Tuberculosis or fungal infection seen on available chest x-ray taken ≤ 3 months of screening or at screening (Exception: documented evidence of completed treatment and clinically resolved). * Known history of human immunodeficiency virus (HIV). Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants Who Achieved Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 12 | Part A: Baseline to Week 12 | HiSCR75 was defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count. |
| Part B: Number of Participants Who Achieved HiSCR75 at Week 16 | Part B: Baseline to Week 16 | HiSCR75 was defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Number of Participants Who Achieved HiSCR90 at Week 16 | Part B: Baseline to Week 16 | HiSCR90 was defined as at least a 90% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count |
| Part B: Number of Participants Who Achieved HiSCR100 at Week 16 | Part B: Baseline to Week 16 | HiSCR100 was defined as at least a 100% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count. |
| Part B: Number of Participants Who Achieved HiSCR50 at Week 16 | Part B: Baseline to Week 16 | HiSCR50 was defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count |
| Part B: Percentage of Participants Who Experienced ≥ 1 Disease Flare Through 16 Weeks of Treatment | Part B: Day 1 through to Week 16 | A flare was defined as ≥ 25% increase in AN count with a minimum increase of 2 AN relative to baseline. Missing data of abscess and inflammatory nodules counts at scheduled visits are imputed assuming monotone missingness pattern. Predictors in the regression model for missing values at Week 4 are Baseline Hurley stage, baseline abscess count, baseline inflammatory nodule count, baseline draining fistula count, sex, race, age, body mass index (BMI) and prior Biologic/JAK inhibitor use for HS. Predictors in the regression model for missing values after Week 4 are all of these variables, plus counts of abscess, inflammatory nodule, and draining fistula at prior scheduled assessment. Missing flare values in both the placebo and izokibep groups are imputed using observed data from the placebo group only. |
| Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Part A: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks | An adverse event (AE) referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events. |
| Part B: Number of Participants Who Achieved at Least a 3-Point Reduction From Baseline in Numeric Rating Scale (NRS) in Patient Global Assessment of Skin Pain at Its Worst at Week 16 Among Participants With Baseline NRS ≥ 4 | Part B: Baseline to Week 16 | The Patient Global Assessment of Skin Pain is a NRS that consists of scores from 0 to 10 with 0 indicating no skin pain and 10 indicating pain as bad as you can imagine. |
| Part B: Number of Participants With TEAEs of Special Interest | Part B: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks | Adverse events of special interest were adverse events in the following categories: candida infection, inflammatory bowel disease, suicidal ideation, malignancies, major cardiovascular and cerebrovascular events, tuberculosis, infections, cytopenias and hypersensitivity reactions. |
| Part B: Number of Participants With TEAEs | Part B: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks | An AE referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. SAEs were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events. |
| Part B: Number of Participants Testing Positive for ADAs | Up to 39 weeks | Blood samples were collected at different time points throughout the study. |
| Part B: Number of Participants With Hurley Stage II at Baseline Who Achieved AN Count of 0, 1, or 2 | Part B: Week 16 | The percentage of participants with baseline Hurley Stage II who achieved AN count of 0, 1, or 2 at Week 16. Hurley stages: Stage 1 - solitary or multiple, isolated abscess formation without scarring or sinus tracts Stage 2 - recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation Stage 3 - diffuse or broad involvement, with multiple interconnected sinus tracts and abscesses. |
| Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs) | Baseline, Week 16, Week 32, Week 39 | Blood samples were collected at different time points throughout the study. |
Countries
Canada, Germany, Hungary, Poland, Spain, United States
Participant flow
Recruitment details
Participants were recruited at different centers in the United States, Canada, Germany, Hungary, Poland, and Spain, and participated from May 2022 to February 2024.
Pre-assignment details
Part A was a single-arm, open-label, proof-of-concept investigation to explore preliminary efficacy and safety of izokibep. Once Part A was fully enrolled, subsequent participants were enrolled into Part B. Part B was a randomized, double-blind, placebo-controlled, parallel-group, dose-finding investigation to evaluate the efficacy, safety, and immunogenicity of izokibep in participants with moderate to severe hidradenitis suppurativa.
Participants by arm
| Arm | Count |
|---|---|
| Part A Izokibep 160 mg QW Participants with moderate to severe HS received open label izokibep 160 mg by SC injection QW in Part A for up to 31 weeks. | 30 |
| Part B Placebo QW/Q2W Then Izokibep QW/Q2W Participants with moderate to severe HS received placebo by SC injection either QW or Q2W for up to 16 weeks. After Week 16, participants who received placebo QW switched to izokibep QW up to Week 31. Participants who received placebo Q2W switched to izokibep Q2W up to Week 30. | 59 |
| Part B Izokibep 160 mg QW Participants with moderate to severe HS received izokibep 160 mg QW by SC injection for 31 weeks. | 57 |
| Part B Izokibep 160 mg Q2W Participants with moderate to severe HS received izokibep 160 mg Q2W by SC injection for 30 weeks. | 59 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Decision by Sponsor | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 6 | 11 | 10 | 6 |
| Overall Study | Withdrawal by Subject | 7 | 14 | 15 | 13 |
Baseline characteristics
| Characteristic | Total | Part A Izokibep 160 mg QW | Part B Izokibep 160 mg Q2W | Part B Placebo QW/Q2W Then Izokibep QW/Q2W | Part B Izokibep 160 mg QW |
|---|---|---|---|---|---|
| Abcess and Inflammatory Nodule (AN) Count Part A | 10.5 Total Abcess/Nodules STANDARD_DEVIATION 7.64 | 10.5 Total Abcess/Nodules STANDARD_DEVIATION 7.64 | — | — | — |
| Abcess and Inflammatory Nodule (AN) Count Part B | 10.4 Total Abcess/Nodules STANDARD_DEVIATION 7.42 | — | 9.9 Total Abcess/Nodules STANDARD_DEVIATION 6.85 | 9.3 Total Abcess/Nodules STANDARD_DEVIATION 5.24 | 11.9 Total Abcess/Nodules STANDARD_DEVIATION 9.5 |
| Abscess Count Part A | 1.7 Abcesses STANDARD_DEVIATION 2.18 | 1.7 Abcesses STANDARD_DEVIATION 2.18 | — | — | — |
| Abscess Count Part B | 1.9 Abcesses STANDARD_DEVIATION 3.67 | — | 1.9 Abcesses STANDARD_DEVIATION 4.86 | 1.8 Abcesses STANDARD_DEVIATION 2.1 | 1.9 Abcesses STANDARD_DEVIATION 3.57 |
| Age, Categorical Part A <=18 years | 0 Participants | 0 Participants | — | — | — |
| Age, Categorical Part A >=65 years | 0 Participants | 0 Participants | — | — | — |
| Age, Categorical Part A Between 18 and 65 years | 30 Participants | 30 Participants | — | — | — |
| Age, Categorical Part B <=18 years | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Part B >=65 years | 3 Participants | — | 1 Participants | 1 Participants | 1 Participants |
| Age, Categorical Part B Between 18 and 65 years | 172 Participants | — | 58 Participants | 58 Participants | 56 Participants |
| Age, Continuous Part A | 38.3 years STANDARD_DEVIATION 9.68 | 38.3 years STANDARD_DEVIATION 9.68 | — | — | — |
| Age, Continuous Part B | 37.6 years STANDARD_DEVIATION 11.2 | — | 40.3 years STANDARD_DEVIATION 10.04 | 37.2 years STANDARD_DEVIATION 11.45 | 35.3 years STANDARD_DEVIATION 11.66 |
| Draining Fistula Count Part A | 1.7 Fistulas STANDARD_DEVIATION 2.35 | 1.7 Fistulas STANDARD_DEVIATION 2.35 | — | — | — |
| Draining Fistula Count Part B | 3.1 Fistulas STANDARD_DEVIATION 4.24 | — | 2.6 Fistulas STANDARD_DEVIATION 3.38 | 3.5 Fistulas STANDARD_DEVIATION 5.18 | 3.0 Fistulas STANDARD_DEVIATION 3.97 |
| Ethnicity (NIH/OMB) Part A Hispanic or Latino | 4 Participants | 4 Participants | — | — | — |
| Ethnicity (NIH/OMB) Part A Not Hispanic or Latino | 26 Participants | 26 Participants | — | — | — |
| Ethnicity (NIH/OMB) Part A Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — |
| Ethnicity (NIH/OMB) Part B Hispanic or Latino | 27 Participants | — | 7 Participants | 9 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Part B Not Hispanic or Latino | 148 Participants | — | 52 Participants | 50 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Part B Unknown or Not Reported | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Inflammatory Nodule Count Part A | 8.8 Nodules STANDARD_DEVIATION 7.2 | 8.8 Nodules STANDARD_DEVIATION 7.2 | — | — | — |
| Inflammatory Nodule Count Part B | 8.5 Nodules STANDARD_DEVIATION 6.22 | — | 7.9 Nodules STANDARD_DEVIATION 4.21 | 7.5 Nodules STANDARD_DEVIATION 5.1 | 10.0 Nodules STANDARD_DEVIATION 8.45 |
| Race (NIH/OMB) Part A American Indian or Alaska Native | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Part A Asian | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Part A Black or African American | 14 Participants | 14 Participants | — | — | — |
| Race (NIH/OMB) Part A More than one race | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Part A Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Part A Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — |
| Race (NIH/OMB) Part A White | 16 Participants | 16 Participants | — | — | — |
| Race (NIH/OMB) Part B American Indian or Alaska Native | 1 Participants | — | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Part B Asian | 4 Participants | — | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Part B Black or African American | 22 Participants | — | 6 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) Part B More than one race | 5 Participants | — | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Part B Native Hawaiian or Other Pacific Islander | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part B Unknown or Not Reported | 0 Participants | — | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part B White | 143 Participants | — | 51 Participants | 47 Participants | 45 Participants |
| Sex: Female, Male Part A Female | 21 Participants | 21 Participants | — | — | — |
| Sex: Female, Male Part A Male | 9 Participants | 9 Participants | — | — | — |
| Sex: Female, Male Part B Female | 115 Participants | — | 36 Participants | 40 Participants | 39 Participants |
| Sex: Female, Male Part B Male | 60 Participants | — | 23 Participants | 19 Participants | 18 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 59 | 0 / 57 | 0 / 59 | 0 / 26 | 0 / 24 | 0 / 53 | 0 / 43 |
| other Total, other adverse events | 25 / 30 | 25 / 59 | 43 / 57 | 34 / 59 | 10 / 26 | 14 / 24 | 9 / 53 | 13 / 43 |
| serious Total, serious adverse events | 2 / 30 | 2 / 59 | 2 / 57 | 1 / 59 | 1 / 26 | 2 / 24 | 0 / 53 | 1 / 43 |
Outcome results
Primary
Part A: Number of Participants Who Achieved Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 12
HiSCR75 was defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count.
Time frame: Part A: Baseline to Week 12
Population: FAS, Part A: all participants who received at lease one dose of study drug in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part A: Number of Participants Who Achieved Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 12 | 12 Participants |
Primary
Part B: Number of Participants Who Achieved HiSCR75 at Week 16
HiSCR75 was defined as at least a 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count.
Time frame: Part B: Baseline to Week 16
Population: FAS, Part B: all participants randomized in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR75 at Week 16 | 16 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR75 at Week 16 | 21 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Who Achieved HiSCR75 at Week 16 | 19 Participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/Janus Kinase (JAK) inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error was estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR75.p-value: 0.3055Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error was estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR75.p-value: 0.6192Cochran-Mantel-Haenszel
Secondary
Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs)
Blood samples were collected at different time points throughout the study.
Time frame: Baseline, Week 16, Week 32, Week 39
Population: ADA Analysis Set: all participants who received at lease one dose of study drug and had both baseline ADA and at least one post-dose ADA measurement in Part A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Izokibep 160 mg QW | Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs) | Week 32 | 15 Participants |
| Part A Izokibep 160 mg QW | Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs) | Baseline | 12 Participants |
| Part A Izokibep 160 mg QW | Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs) | Week 16 | 11 Participants |
| Part A Izokibep 160 mg QW | Part A: Number of Participants Testing Positive for Anti-drug Antibodies (ADAs) | Week 39 | 17 Participants |
Secondary
Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Time frame: Part A: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks
Population: Safety analysis set (SAS): all participants who received at lease one dose of study drug in Part A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Izokibep 160 mg QW | Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 26 Participants |
| Part A Izokibep 160 mg QW | Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 2 Participants |
Secondary
Part B: Number of Participants Testing Positive for ADAs
Blood samples were collected at different time points throughout the study.
Time frame: Up to 39 weeks
Population: ADA Analysis Set: all participants who received at lease one dose of study drug and had both baseline ADA and at least one post-dose ADA measurement in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Baseline | 27 Participants |
| Part A Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Week 16 | 21 Participants |
| Part A Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Week 32 | 13 Participants |
| Part A Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Week 39 | 17 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Week 39 | 32 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Baseline | 29 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Week 32 | 35 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Testing Positive for ADAs | Week 16 | 29 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Testing Positive for ADAs | Week 39 | 15 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Testing Positive for ADAs | Week 16 | 39 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Testing Positive for ADAs | Week 32 | 12 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Testing Positive for ADAs | Baseline | 36 Participants |
Secondary
Part B: Number of Participants Who Achieved at Least a 3-Point Reduction From Baseline in Numeric Rating Scale (NRS) in Patient Global Assessment of Skin Pain at Its Worst at Week 16 Among Participants With Baseline NRS ≥ 4
The Patient Global Assessment of Skin Pain is a NRS that consists of scores from 0 to 10 with 0 indicating no skin pain and 10 indicating pain as bad as you can imagine.
Time frame: Part B: Baseline to Week 16
Population: FAS, Part B: all participants randomized in Part B who had a baseline NRS ≥ 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants Who Achieved at Least a 3-Point Reduction From Baseline in Numeric Rating Scale (NRS) in Patient Global Assessment of Skin Pain at Its Worst at Week 16 Among Participants With Baseline NRS ≥ 4 | 4 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Who Achieved at Least a 3-Point Reduction From Baseline in Numeric Rating Scale (NRS) in Patient Global Assessment of Skin Pain at Its Worst at Week 16 Among Participants With Baseline NRS ≥ 4 | 5 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Who Achieved at Least a 3-Point Reduction From Baseline in Numeric Rating Scale (NRS) in Patient Global Assessment of Skin Pain at Its Worst at Week 16 Among Participants With Baseline NRS ≥ 4 | 9 Participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.p-value: 0.4031Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.p-value: 0.0327Cochran-Mantel-Haenszel
Secondary
Part B: Number of Participants Who Achieved HiSCR100 at Week 16
HiSCR100 was defined as at least a 100% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count.
Time frame: Part B: Baseline to Week 16
Population: FAS, Part B: all participants randomized in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR100 at Week 16 | 7 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR100 at Week 16 | 15 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Who Achieved HiSCR100 at Week 16 | 11 Participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR100.p-value: 0.0514Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR100.p-value: 0.3322Cochran-Mantel-Haenszel
Secondary
Part B: Number of Participants Who Achieved HiSCR50 at Week 16
HiSCR50 was defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count
Time frame: Part B: Baseline to Week 16
Population: FAS, Part B: all participants randomized in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR50 at Week 16 | 22 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR50 at Week 16 | 26 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Who Achieved HiSCR50 at Week 16 | 26 Participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR50.p-value: 0.3258Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR50.p-value: 0.4068Cochran-Mantel-Haenszel
Secondary
Part B: Number of Participants Who Achieved HiSCR90 at Week 16
HiSCR90 was defined as at least a 90% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining fistula count
Time frame: Part B: Baseline to Week 16
Population: FAS, Part B: all participants randomized in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR90 at Week 16 | 9 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants Who Achieved HiSCR90 at Week 16 | 15 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants Who Achieved HiSCR90 at Week 16 | 12 Participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR90.p-value: 0.1606Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Non-response imputation was used for participants with missing HiSCR90.p-value: 0.5116Cochran-Mantel-Haenszel
Secondary
Part B: Number of Participants With Hurley Stage II at Baseline Who Achieved AN Count of 0, 1, or 2
The percentage of participants with baseline Hurley Stage II who achieved AN count of 0, 1, or 2 at Week 16. Hurley stages: Stage 1 - solitary or multiple, isolated abscess formation without scarring or sinus tracts Stage 2 - recurrent abscesses, single or multiple widely separated lesions, with sinus tract formation Stage 3 - diffuse or broad involvement, with multiple interconnected sinus tracts and abscesses.
Time frame: Part B: Week 16
Population: FAS, Part B: all participants randomized in Part B, inclusive only of participants with Hurley Stage II at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants With Hurley Stage II at Baseline Who Achieved AN Count of 0, 1, or 2 | 15 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants With Hurley Stage II at Baseline Who Achieved AN Count of 0, 1, or 2 | 18 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants With Hurley Stage II at Baseline Who Achieved AN Count of 0, 1, or 2 | 14 Participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.p-value: 0.5422Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.p-value: 0.6569Cochran-Mantel-Haenszel
Secondary
Part B: Number of Participants With TEAEs
An AE referred to any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. SAEs were untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Time frame: Part B: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks
Population: SAS: all randomized participants who received at least one dose of study drug in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants With TEAEs | Any TEAE | 40 Participants |
| Part A Izokibep 160 mg QW | Part B: Number of Participants With TEAEs | Serious TEAE | 2 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants With TEAEs | Any TEAE | 49 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants With TEAEs | Serious TEAE | 2 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants With TEAEs | Any TEAE | 48 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants With TEAEs | Serious TEAE | 1 Participants |
| Part B Placebo/Izokibep 160 mg QW (Week 16 to 31) | Part B: Number of Participants With TEAEs | Any TEAE | 17 Participants |
| Part B Placebo/Izokibep 160 mg QW (Week 16 to 31) | Part B: Number of Participants With TEAEs | Serious TEAE | 2 Participants |
| Part B Placebo/Izokibep 160 mg Q2W (Week 16 to 30) | Part B: Number of Participants With TEAEs | Any TEAE | 16 Participants |
| Part B Placebo/Izokibep 160 mg Q2W (Week 16 to 30) | Part B: Number of Participants With TEAEs | Serious TEAE | 1 Participants |
| Part B: Izokibep 160 mg QW (Week 16 to 31) | Part B: Number of Participants With TEAEs | Any TEAE | 27 Participants |
| Part B: Izokibep 160 mg QW (Week 16 to 31) | Part B: Number of Participants With TEAEs | Serious TEAE | 1 Participants |
| Part B: Izokibep 160 mg Q2W (Week 16 to 30) | Part B: Number of Participants With TEAEs | Any TEAE | 25 Participants |
| Part B: Izokibep 160 mg Q2W (Week 16 to 30) | Part B: Number of Participants With TEAEs | Serious TEAE | 0 Participants |
Secondary
Part B: Number of Participants With TEAEs of Special Interest
Adverse events of special interest were adverse events in the following categories: candida infection, inflammatory bowel disease, suicidal ideation, malignancies, major cardiovascular and cerebrovascular events, tuberculosis, infections, cytopenias and hypersensitivity reactions.
Time frame: Part B: Screening (Day -28) to Follow-up (Week 45), for a total of 49 weeks
Population: SAS: all randomized participants who received at least one dose of study drug in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Number of Participants With TEAEs of Special Interest | 4 Participants |
| Part B Izokibep 160 mg QW | Part B: Number of Participants With TEAEs of Special Interest | 2 Participants |
| Part B Izokibep 160 mg Q2W | Part B: Number of Participants With TEAEs of Special Interest | 1 Participants |
| Part B Placebo/Izokibep 160 mg QW (Week 16 to 31) | Part B: Number of Participants With TEAEs of Special Interest | 1 Participants |
| Part B Placebo/Izokibep 160 mg Q2W (Week 16 to 30) | Part B: Number of Participants With TEAEs of Special Interest | 2 Participants |
| Part B: Izokibep 160 mg QW (Week 16 to 31) | Part B: Number of Participants With TEAEs of Special Interest | 0 Participants |
| Part B: Izokibep 160 mg Q2W (Week 16 to 30) | Part B: Number of Participants With TEAEs of Special Interest | 2 Participants |
Secondary
Part B: Percentage of Participants Who Experienced ≥ 1 Disease Flare Through 16 Weeks of Treatment
A flare was defined as ≥ 25% increase in AN count with a minimum increase of 2 AN relative to baseline. Missing data of abscess and inflammatory nodules counts at scheduled visits are imputed assuming monotone missingness pattern. Predictors in the regression model for missing values at Week 4 are Baseline Hurley stage, baseline abscess count, baseline inflammatory nodule count, baseline draining fistula count, sex, race, age, body mass index (BMI) and prior Biologic/JAK inhibitor use for HS. Predictors in the regression model for missing values after Week 4 are all of these variables, plus counts of abscess, inflammatory nodule, and draining fistula at prior scheduled assessment. Missing flare values in both the placebo and izokibep groups are imputed using observed data from the placebo group only.
Time frame: Part B: Day 1 through to Week 16
Population: FAS, Part B: all participants randomized in Part B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Izokibep 160 mg QW | Part B: Percentage of Participants Who Experienced ≥ 1 Disease Flare Through 16 Weeks of Treatment | 22.32 Percentage of participants |
| Part B Izokibep 160 mg QW | Part B: Percentage of Participants Who Experienced ≥ 1 Disease Flare Through 16 Weeks of Treatment | 18.29 Percentage of participants |
| Part B Izokibep 160 mg Q2W | Part B: Percentage of Participants Who Experienced ≥ 1 Disease Flare Through 16 Weeks of Treatment | 14.93 Percentage of participants |
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg QW arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Missing data of abscess and inflammatory nodules counts at scheduled visits are imputed assuming monotone missingness pattern.p-value: 0.3329Cochran-Mantel-Haenszel
Comparison: The common risk difference between placebo QW/Q2W and the izokibep 160 mg Q2W arm among the four strata, prior biologic/JAK inhibitor use for HS (Yes/No) and Hurley Stage (II or III), used for randomization and associated standard error will be estimated by combining the observed risk differences using Cochran-Mantel-Haenszel weighting.~Missing data of abscess and inflammatory nodules counts at scheduled visits are imputed assuming monotone missingness pattern.p-value: 0.5882Cochran-Mantel-Haenszel