Psoriatic Arthritis
Conditions
Keywords
psoriatic arthritis (PsA), psoriasis, inflammatory arthritis, enthesitis
Brief summary
Izokibep is a potent and selective inhibitor of interleukin (IL)-17A that is being developed for treatment of psoriatic arthritis (PsA). This study will evaluate the efficacy of izokibep in subjects with PsA.
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. * Subject must be ≥18 (or the legal age of consent in the jurisdiction in which the study is taking place) and ≤75 years of age, at the time of signing the informed consent. Type of Subject and Disease Characteristics * Clinical diagnosis of psoriatic arthritis (PsA) with symptom onset at least 6 months prior to first dose of study drug and fulfillment of the ClASsification for Psoriatic ARthritis (CASPAR) criteria at Screening. * Active PsA defined as ≥3 tender joints (based on 68 joint counts) and ≥3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits * Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) negative at screening. * Subject must have had an inadequate response, intolerance, or contraindication to at least one of the following: 1. nonsteroidal anti-inflammatory drug (NSAID) 2. conventional-synthetic disease-modifying anti-rheumatic drugs (csDMARD) (i.e. methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, cyclosporine A) 3. tumor necrosis factor-alpha inhibitor(s) (TNFi) (e.g. adalimumab, infliximab, etanercept, golimumab, certolizumab). * For subjects using methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, or apremilast, treated for ≥3 months and a stable dose (not to exceed 25 mg methotrexate per week, 20 mg leflunomide per day, sulfasalazine 3 g per day, hydroxychloroquine 400 mg per day, or apremilast 60 mg per day) for ≥4 weeks prior to first dose of study drug. * For subjects using corticosteroids, must have been on a stable dose and regimen and not to exceed 7.5 mg per day of prednisone (or other corticosteroid equivalent to 7.5 mg per day of prednisone) for ≥4 weeks prior to first dose of study drug. * Subjects using NSAIDs, or low potency opioid medications (tramadol, paracetamol in combination with hydrocodone or with codeine) must have been on a stable dose and regimen for ≥2 weeks prior to first dose of study drug. Other Inclusions * No known history of active tuberculosis (TB). * Subject has a negative TB test at screening
Exclusion criteria
Disease-related Medical Conditions * Any history or current confirmed diagnosis of inflammatory bowel disease (IBD) OR * Any of the following symptoms (of unknown etiology) or any signs or symptoms within the last year that in the opinion of the Investigator may be suggestive of IBD, with fecal calprotectin ≥ 500 μg/g; OR if fecal calprotectin \>150 to \<500 μg/g without confirmed approval from a GI consult that an IBD diagnosis is clinically unlikely when the following clinical signs and symptoms are present: 1. prolonged or recurrent diarrhea 2. prolonged or recurrent abdominal pain 3. blood in stool * History of fibromyalgia, or any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than psoriatic arthritis (PsA) (including, but not limited to rheumatoid arthritis, gout, connective tissue diseases). Prior history of axial spondyloarthritis or fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis was made incorrectly. Prior history of reactive arthritis or axial spondyloarthritis is permitted if an additional diagnosis of PsA is made. Chronic osteoarthritis symptoms that in the Investigator's opinion may interfere with study assessments. * Uncontrolled, clinically significant system disease * Malignancy within 5 years * Severe, uncontrolled, medically unstable mood disorder, such as severe depression. * History or evidence of any clinically significant disorder (including psychiatric), condition, or disease that, in the opinion of the investigator, may pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. * Active infection or history of certain infections * Candida infection requiring systemic treatment within 3 months prior to first dose of study drug. * Tuberculosis or fungal infection seen on available chest x-ray taken within 3 months prior to first dose of study drug or at screening (Exception: documented evidence of completed treatment and clinically resolved). * Known history of human immunodeficiency virus (HIV) or positive HIV test at screening. Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16 | Week 16 | ACR50 is a clinical trial measure for PsA, indicating a 50% improvement in symptoms. To qualify, participants must show a 50% reduction in tender and swollen joint counts plus improvements in three of five additional criteria, including pain, global assessments, physical function, and inflammatory markers. ACR50 is binary-patients either meet it or not. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16 | Baseline and Week 16 | LEI is a clinical tool used to assess enthesitis in conditions like psoriatic arthritis and spondyloarthritis. It evaluates six sites: bilateral lateral epicondyles, medial femoral condyles, and achilles tendons. Each site is scored 0 (no pain) or 1 (pain on pressure), with a total score ranging from a minimum of 0 to a maximum of 6, where higher scores indicate more severe enthesitis. |
| Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16 | Week 16 | A participants was classified as being in MDA when at least five of the following seven criteria were met: * Tender joint count based on 68 joints (TJC68) ≤ 1 * Swollen joint count based on 66 joints (SJC66) ≤ 1 * PASI ≤ 1 or BSA ≤ 3% * Participant's Pain Assessment (Visual Analogue Scale \[VAS\]) ≤ 15 mm * Participant's Global Activity VAS ≤ 20 mm (corresponding to participant's Global Assessment of Disease Activity) * Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ 0.5 * Tender enthesitis points ≤ 1 out of 6 sites assessed by the LEI. |
| Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16 | Week 16 | ACR20 is a clinical trial measure for PsA, indicating a 20% improvement in symptoms. To qualify, participants must show a 20% reduction in tender and swollen joint counts plus improvements in three of five additional criteria, including pain, global assessments, physical function, and inflammatory markers. ACR20 is binary-patients either meet it or not. |
| Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16 | Week 16 | The PsAID consists of nine items, each scored on a numeric rating scale (0-10), covering key aspects of disease burden, including pain, fatigue, skin problems, work/leisure activities, functional capacity, sleep disturbance, anxiety, coping, and social participation. The total score is calculated as a weighted sum of these individual items, with higher scores indicating a greater impact of the disease. The minimum score is 0 (no disease impact), while the maximum is 10 (worst possible disease impact). Reaching an improvement was considered an increase of 3 units from baseline score. |
| Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16 | Baseline and Week 16 | PASI is a tool used in clinical trials to measure the severity and extent of psoriasis. Scores range from a minimum of 0 to a maximum of 72, with higher scores indicating more severe disease. |
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | Up to Week 16, or 4 weeks after participant's last dose in case of treatment discontinuation | An AE was any untoward medical occurrence in a participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received study treatment. Clinically significant changes in vital signs, electrocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs. TEAEs were considered serious if they led to death, were life-threatening, required hospitalization or its prolongation, caused disability, resulted in congenital anomalies or were considered medically important. The events of special interest monitored were : candida infection; inflammatory bowel disease; suicidal ideation; malignancies; major adverse cardiovascular and cerebrovascular events (cerebrovascular accident and transient ischemic attack, nonfatal myocardial infarction or unstable angina, cardiovascular death); tuberculosis; infections (opportunistic, serious, or fungal); cytopenia; systemic hypersensitivity reactions. |
| Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | First dose of study treatment on or after Week 16 up to Week 55 | An AE was any untoward medical occurrence in a participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received study treatment. Clinically significant changes in vital signs, electrocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs. TEAEs were considered serious if they led to death, were life-threatening, required hospitalization or its prolongation, caused disability, resulted in congenital anomalies or were considered medically important. The events of special interest monitored were : candida infection; inflammatory bowel disease; suicidal ideation; malignancies; major adverse cardiovascular and cerebrovascular events (cerebrovascular accident and transient ischemic attack, nonfatal myocardial infarction or unstable angina, cardiovascular death); tuberculosis; infections (opportunistic, serious, or fungal); cytopenia; systemic hypersensitivity reactions. |
| Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Baseline to Week 65 | Blood samples were collected at different timepoints throughout the study. ADA is considered Positive if any titer value is available. |
| Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16 | Baseline and Week 16 | The HAQ-DI consists of 20 questions divided into eight categories: dressing, arising, eating, walking, hygiene, reaching, grip, and other activities. Each item is scored on a scale from 0 to 3, where 0 = no difficulty, 1 = some difficulty, 2 = much difficulty, and 3 = unable to perform. The final HAQ-DI score is calculated as the average of the highest scores in each category, resulting in a range from 0 (no disability) to 3 (severe disability). Higher scores indicate greater functional impairment. A negative change indicates an improvement in functional impairment. |
Countries
Bulgaria, Canada, Czechia, Germany, Hungary, Poland, Spain, United States
Participant flow
Recruitment details
A total of 351 participants with Psoriatic Arthritis (PsA) symptoms were recruited in Canada, United States, Bulgaria, Czech Republic, Germany, Hungary, Poland, and Spain between November 2022 and August 2024.
Pre-assignment details
This study was divided into two Periods. In Period 1 (Phase 2b portion of the study), participants received either izokibep or placebo, until Week 16. Period 2 (Phase 3 portion of the study) lasted until Week 52. Participants who received placebo QW during Period 1 started receiving izokibep QW during Period 2 and participants who received izokibep during Period 1 continued to receive izokibep at the same dosing frequency in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| Period 1: Placebo QW Participants received placebo as a SC injection QW up to Week 16. | 118 |
| Izokibep 80 mg Q4W Participants received izokibep 80 mg as a SC injection every 4 weeks (Q4W) up to Week 52. Matching placebo QW was administered for weeks in-between izokibep to maintain the blind. | 8 |
| Izokibep 160 mg Q2W Participants received izokibep 160 mg as a SC injection every Q2W up to Week 52. Matching placebo QW was administered for weeks in-between izokibep to maintain the blind. | 113 |
| Izokibep 160 mg QW Participants received izokibep 160 mg as a SC injection QW up to Week 52. | 112 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 | 7 | 2 |
| Overall Study | Termination of Study By Sponsor | 37 | 4 | 40 | 38 |
| Overall Study | Withdrawal by Subject | 14 | 0 | 9 | 20 |
Baseline characteristics
| Characteristic | Period 1: Placebo QW | Izokibep 80 mg Q4W | Izokibep 160 mg Q2W | Izokibep 160 mg QW | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.6 Years STANDARD_DEVIATION 11.74 | 63.1 Years STANDARD_DEVIATION 9.4 | 49.5 Years STANDARD_DEVIATION 13.26 | 51.8 Years STANDARD_DEVIATION 12.2 | 51.6 Years STANDARD_DEVIATION 12.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 1 Participants | 14 Participants | 7 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 105 Participants | 7 Participants | 99 Participants | 104 Participants | 315 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 0 participants | 2 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 0 participants | 2 participants | 2 participants | 7 participants |
| Race/Ethnicity, Customized More than one race | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 2 participants | 0 participants | 1 participants | 0 participants | 3 participants |
| Race/Ethnicity, Customized White | 110 participants | 8 participants | 108 participants | 109 participants | 335 participants |
| Sex: Female, Male Female | 67 Participants | 5 Participants | 46 Participants | 48 Participants | 166 Participants |
| Sex: Female, Male Male | 51 Participants | 3 Participants | 67 Participants | 64 Participants | 185 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 118 | 0 / 114 | 0 / 8 | 0 / 113 | 0 / 112 |
| other Total, other adverse events | 9 / 118 | 65 / 114 | 6 / 8 | 78 / 113 | 84 / 112 |
| serious Total, serious adverse events | 1 / 118 | 4 / 114 | 2 / 8 | 8 / 113 | 4 / 112 |
Outcome results
Primary
Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16
ACR50 is a clinical trial measure for PsA, indicating a 50% improvement in symptoms. To qualify, participants must show a 50% reduction in tender and swollen joint counts plus improvements in three of five additional criteria, including pain, global assessments, physical function, and inflammatory markers. ACR50 is binary-patients either meet it or not.
Time frame: Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Placebo QW | Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16 | 18 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16 | 4 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16 | 49 Participants |
| Izokibep 160 mg QW | Number of Participants Who Achieved 50% Improvement in American College of Rheumatology (ACR50) at Week 16 | 45 Participants |
p-value: 0.0377Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16
The HAQ-DI consists of 20 questions divided into eight categories: dressing, arising, eating, walking, hygiene, reaching, grip, and other activities. Each item is scored on a scale from 0 to 3, where 0 = no difficulty, 1 = some difficulty, 2 = much difficulty, and 3 = unable to perform. The final HAQ-DI score is calculated as the average of the highest scores in each category, resulting in a range from 0 (no disability) to 3 (severe disability). Higher scores indicate greater functional impairment. A negative change indicates an improvement in functional impairment.
Time frame: Baseline and Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Period 1: Placebo QW | Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16 | -0.14 Score on scale |
| Izokibep 80 mg Q4W | Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16 | -0.03 Score on scale |
| Izokibep 160 mg Q2W | Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16 | -0.30 Score on scale |
| Izokibep 160 mg QW | Change in Physical Function as Assessed by HAQ-DI From Baseline to Week 16 | -0.31 Score on scale |
p-value: 0.51495% CI: [-0.22, 0.44]Mixed model repeated measures analysis
p-value: 0.0195% CI: [-0.28, -0.04]Mixed model repeated measures analysis
p-value: 0.00695% CI: [-0.29, -0.05]Mixed model repeated measures analysis
Secondary
Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16
ACR20 is a clinical trial measure for PsA, indicating a 20% improvement in symptoms. To qualify, participants must show a 20% reduction in tender and swollen joint counts plus improvements in three of five additional criteria, including pain, global assessments, physical function, and inflammatory markers. ACR20 is binary-patients either meet it or not.
Time frame: Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Placebo QW | Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16 | 41 Participants |
| Izokibep 80 mg Q4W | Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16 | 6 Participants |
| Izokibep 160 mg Q2W | Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16 | 72 Participants |
| Izokibep 160 mg QW | Number of Participants Achieving 20% Improvement in ACR (ACR20) at Week 16 | 66 Participants |
p-value: 0.0106Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.0002Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16
A participants was classified as being in MDA when at least five of the following seven criteria were met: * Tender joint count based on 68 joints (TJC68) ≤ 1 * Swollen joint count based on 66 joints (SJC66) ≤ 1 * PASI ≤ 1 or BSA ≤ 3% * Participant's Pain Assessment (Visual Analogue Scale \[VAS\]) ≤ 15 mm * Participant's Global Activity VAS ≤ 20 mm (corresponding to participant's Global Assessment of Disease Activity) * Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ 0.5 * Tender enthesitis points ≤ 1 out of 6 sites assessed by the LEI.
Time frame: Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Placebo QW | Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16 | 17 Participants |
| Izokibep 80 mg Q4W | Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16 | 3 Participants |
| Izokibep 160 mg Q2W | Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16 | 47 Participants |
| Izokibep 160 mg QW | Number of Participants Achieving Minimal Disease Activity (MDA) at Week 16 | 46 Participants |
p-value: 0.1654Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2
An AE was any untoward medical occurrence in a participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received study treatment. Clinically significant changes in vital signs, electrocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs. TEAEs were considered serious if they led to death, were life-threatening, required hospitalization or its prolongation, caused disability, resulted in congenital anomalies or were considered medically important. The events of special interest monitored were : candida infection; inflammatory bowel disease; suicidal ideation; malignancies; major adverse cardiovascular and cerebrovascular events (cerebrovascular accident and transient ischemic attack, nonfatal myocardial infarction or unstable angina, cardiovascular death); tuberculosis; infections (opportunistic, serious, or fungal); cytopenia; systemic hypersensitivity reactions.
Time frame: First dose of study treatment on or after Week 16 up to Week 55
Population: Safety Analysis Set: All participants randomized who received at least one administration of test material during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: Placebo QW | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | TEAEs | 89 Participants |
| Period 1: Placebo QW | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | AEs of Special Interest | 3 Participants |
| Period 1: Placebo QW | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | Serious TEAEs | 4 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | TEAEs | 5 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | AEs of Special Interest | 1 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | Serious TEAEs | 1 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | Serious TEAEs | 7 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | TEAEs | 67 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | AEs of Special Interest | 5 Participants |
| Izokibep 160 mg QW | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | TEAEs | 67 Participants |
| Izokibep 160 mg QW | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | AEs of Special Interest | 2 Participants |
| Izokibep 160 mg QW | Number of Participants Who Experienced TEAEs, Serious TEAEs and AE of Special Interest During Period 2 | Serious TEAEs | 2 Participants |
Secondary
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1
An AE was any untoward medical occurrence in a participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received study treatment. Clinically significant changes in vital signs, electrocardiograms and laboratory tests recorded after treatment administration were documented as TEAEs. TEAEs were considered serious if they led to death, were life-threatening, required hospitalization or its prolongation, caused disability, resulted in congenital anomalies or were considered medically important. The events of special interest monitored were : candida infection; inflammatory bowel disease; suicidal ideation; malignancies; major adverse cardiovascular and cerebrovascular events (cerebrovascular accident and transient ischemic attack, nonfatal myocardial infarction or unstable angina, cardiovascular death); tuberculosis; infections (opportunistic, serious, or fungal); cytopenia; systemic hypersensitivity reactions.
Time frame: Up to Week 16, or 4 weeks after participant's last dose in case of treatment discontinuation
Population: Safety Analysis Set: All participants randomized who received at least one administration of test material during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: Placebo QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | TEAEs | 48 Participants |
| Period 1: Placebo QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | AEs of Special Interest | 2 Participants |
| Period 1: Placebo QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | Serious TEAEs | 1 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | TEAEs | 6 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | AEs of Special Interest | 1 Participants |
| Izokibep 80 mg Q4W | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | Serious TEAEs | 2 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | Serious TEAEs | 2 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | TEAEs | 76 Participants |
| Izokibep 160 mg Q2W | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | AEs of Special Interest | 5 Participants |
| Izokibep 160 mg QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | TEAEs | 82 Participants |
| Izokibep 160 mg QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | AEs of Special Interest | 6 Participants |
| Izokibep 160 mg QW | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and AE of Special Interest During Period 1 | Serious TEAEs | 3 Participants |
Secondary
Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result
Blood samples were collected at different timepoints throughout the study. ADA is considered Positive if any titer value is available.
Time frame: Baseline to Week 65
Population: ADA Analysis Set: Included all participants include who received at least one administration of izokibep and had both a baseline ADA measurement and at least one post-dose ADA measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Baseline | 56 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 2 | 56 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 4 | 56 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 12 | 53 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 16 | 54 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 24 | 40 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 36 | 62 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 52 | 65 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Follow-up Visit - Week 59 | 76 Participants |
| Period 1: Placebo QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | End of Study - Week 65 | 49 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 4 | 4 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Follow-up Visit - Week 59 | 6 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 12 | 2 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 16 | 6 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 24 | 5 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 36 | 7 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | End of Study - Week 65 | 2 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 52 | 7 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Baseline | 4 Participants |
| Izokibep 80 mg Q4W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 2 | 3 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 52 | 63 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 36 | 67 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | End of Study - Week 65 | 31 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Baseline | 57 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 12 | 55 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 24 | 70 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Follow-up Visit - Week 59 | 67 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 2 | 61 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 16 | 57 Participants |
| Izokibep 160 mg Q2W | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 4 | 58 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 16 | 57 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 52 | 68 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 24 | 75 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | End of Study - Week 65 | 40 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 36 | 76 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 2 | 54 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 4 | 55 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Week 12 | 51 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Baseline | 54 Participants |
| Izokibep 160 mg QW | Number of Participants With a Positive Treatment-emergent Anti-drug Antibody (ADA) Result | Follow-up Visit - Week 59 | 77 Participants |
Secondary
Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16
PASI is a tool used in clinical trials to measure the severity and extent of psoriasis. Scores range from a minimum of 0 to a maximum of 72, with higher scores indicating more severe disease.
Time frame: Baseline and Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.~Only participants with ≥ 3% BSA psoriasis at baseline were analyzed for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Placebo QW | Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16 | 7 Participants |
| Izokibep 80 mg Q4W | Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16 | 3 Participants |
| Izokibep 160 mg Q2W | Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16 | 37 Participants |
| Izokibep 160 mg QW | Number of Participants With Baseline ≥ 3% Body Surface Area (BSA) Psoriasis Who Achieved a 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI90) at Week 16 | 38 Participants |
p-value: 0.0483Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16
LEI is a clinical tool used to assess enthesitis in conditions like psoriatic arthritis and spondyloarthritis. It evaluates six sites: bilateral lateral epicondyles, medial femoral condyles, and achilles tendons. Each site is scored 0 (no pain) or 1 (pain on pressure), with a total score ranging from a minimum of 0 to a maximum of 6, where higher scores indicate more severe enthesitis.
Time frame: Baseline and Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.~Only participants with LEI \> 0 at baseline were analyzed for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Placebo QW | Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16 | 35 Participants |
| Izokibep 80 mg Q4W | Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16 | 4 Participants |
| Izokibep 160 mg Q2W | Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16 | 38 Participants |
| Izokibep 160 mg QW | Number of Participants With Baseline Enthesitis > 0 With Resolution of Enthesitis (Leeds Enthesitis Index [LEI] = 0) at Week 16 | 30 Participants |
p-value: 0.0883Cochran-Mantel-Haenszel
p-value: 0.2713Cochran-Mantel-Haenszel
p-value: 0.8872Cochran-Mantel-Haenszel
Secondary
Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16
The PsAID consists of nine items, each scored on a numeric rating scale (0-10), covering key aspects of disease burden, including pain, fatigue, skin problems, work/leisure activities, functional capacity, sleep disturbance, anxiety, coping, and social participation. The total score is calculated as a weighted sum of these individual items, with higher scores indicating a greater impact of the disease. The minimum score is 0 (no disease impact), while the maximum is 10 (worst possible disease impact). Reaching an improvement was considered an increase of 3 units from baseline score.
Time frame: Week 16
Population: Full Analysis Set: all participants randomized who received at least one administration of test material was included in the summaries and analyses.~Only participants with PsAID ≥ 3 at baseline were analyzed for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1: Placebo QW | Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16 | 12 Participants |
| Izokibep 80 mg Q4W | Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16 | 3 Participants |
| Izokibep 160 mg Q2W | Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16 | 43 Participants |
| Izokibep 160 mg QW | Number of Participants With Baseline Psoriatic Arthritis Impact of Disease (PsAID) Score ≥ 3 With Improvement in PsAID Score at Week 16 | 40 Participants |
p-value: 0.1147Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel