A Study to Investigate ABP 654 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy, safety, and immunogenicity of ABP 654 compared with ustekinumab in participants with moderate to severe plaque psoriasis.

Detailed Description
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This is a multicenter study and will enroll approximately 542 participants. The total duration of study participation for each participant will be 56 weeks, with up to 4 weeks for screening, and for 52 weeks after the first administration of either ABP 654 or ustekinumab. After confirmation of eligibility, all participants will be randomized in a 1:1 ratio into 2 treatment groups (Group A will receive ABP 654, and Group B will receive ustekinumab) stratified by prior biologic use for psoriasis (yes versus [vs] no), geographic region, and baseline body weight (BW). Based on the psoriasis area and severity index (PASI) score (to determine better improvement or partial improvement) at week 28, the participants in the study will proceed as follows: Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered to have completed the study and will complete end of study procedures (ie, week 52 procedures), and those unable to complete week 28 visit, or did not have a PASI assessment completed, will be discontinued from the study. Participants who achieve PASI 75 response or better improvement will continue on the study and will be re-randomized in a blinded fashion such that participants initially randomized to Group A (ABP 654) will continue to receive ABP 654 and those in Group B (ustekinumab) will re-randomized, to either continue on ustekinumab (Treatment Group B1) or switch to ABP 654 (Treatment Group B2). Participants with PASI 50 response or better but less than PASI 75 response and on the Investigator's decision, participants will continue on the originally assigned treatment with dose intensification and will not be re-randomized. However, participants that do not dose intensify will be re-randomized.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind Study Evaluating the Efficacy and Safety of ABP 654 Compared With Ustekinumab in Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: ABP 654
* Drug: Ustekinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Stable moderate to severe plaque psoriasis for at least 6 months Baseline score of PASI >= 12, involvement of >= 10% BSA, and sPGA >= 3 at screening and at baseline Candidate for phototherapy or systemic therapy Previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional anti-psoriatic systemic therapy Female participants should have negative serum pregnancy test during screening and a negative urine pregnancy test at baseline No known history of latent or active tuberculosis (TB), and has a negative test for TB during screening (with negative purified protein derivative (PPD), and Negative Quantiferon®/T-spot test) Participants with a positive purified protein derivative and a history of Bacillus Calmette-Guérin (BCG) vaccination are allowed with a negative Quantiferon®/T-spot® Participants with a positive PPD test (without history of BCG vaccination) or participants with a positive or indeterminate Quantiferon®/T-spot test are allowed if they have all of the following: No symptoms per TB worksheet provided by the sponsor Documented history of adequate prophylaxis initiation prior to receiving investigational product (IP) in accordance with local recommendations No known exposure to a case of active TB after most recent prophylaxis No evidence of active TB on chest radiograph within 3 months prior to the first dose of IP Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Skin disease related conditions such as, Erythrodermic psoriasis (PsO), pustular PsO, guttate PsO, medication induced PsO, or other skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of IP on PsO Participant has an active infection, recurrent or chronic infections, serious infection or history of infections Known history of human immunodeficiency virus Hepatitis B surface antigen or hepatitis C virus antibody positivity at screening Uncontrolled, clinically significant systemic disease such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension Moderate to severe heart failure (New York Heart Associate class III/IV) Known hypersensitivity to the IP or to any of the excipients Any abnormal laboratory parameters at screening, as defined in protocol Previous treatment with any agent specifically targeting interleukin (IL)-12 or IL-23 Received biologic treatment for psoriasis within the previous month or 5 drug half-lives prior to randomization Received non-biologic systemic psoriasis therapy within 4 weeks prior to randomization Received Ultra-violet A (UVA) phototherapy (with or without psoralen) or excimer laser within 4 weeks prior to randomization, or ultra-violet B (UVB) phototherapy within 2 weeks prior to randomization Received topical psoriasis treatment within 2 weeks prior to randomization (exception: upper mid-strength to least potent [class III to VII] topical steroids permitted on the palms, soles, face, and intertriginous areas; bland emollients) Received live viral or live bacterial vaccination within 2 weeks prior to randomization Received BCG vaccination within 1 year prior to randomization Other investigational procedures within 4 weeks prior to randomization and during the study Participants not agreeing to follow protocol defined contraceptives procedures Participants likely not to be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group A (ABP 654)<br>Participants will receive subcutaneous (SC) injection of ABP 654, 45 mg (baseline BW less than equal to [<=] 100 kg) or 90 mg (baseline BW greater than [>] 100 kg) at weeks 0, 4, and 16. Further from week 28 participants will receive ABP 654 (same dose) every 12 weeks (Q12W) at weeks 28 and 40 or may receive dose intensification Q8W at weeks 28, 36, and 44, depending on PASI score. | Drug: ABP 654<br>* Participants will receive SC injection of ABP 654.<br>|
| Experimental: Treatment Group B (Ustekinumab - ABP 654)<br>Participants will receive SC injection of ustekinumab,45 mg (baseline BW <= 100 kg) or 90 mg (baseline BW > 100 kg) at weeks 0, 4, and 16. At week 28, participants will be re-randomized to continue on ustekinumab (Treatment group B1), or to receive ABP 654 (Treatment group B2) on weeks 28 and 40. Depending on PASI score, some participants may not be re-randomized and may receive dose intensification with ustekinumab Q8W at weeks 28, 36, and 44. | Drug: ABP 654<br>* Participants will receive SC injection of ABP 654.<br>Drug: Ustekinumab<br>* Participants will receive SC injection of ustekinumab.<br>* Other names: Stelara®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI Percent Change From Baseline to Week 12 | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale [0 = clear; 1-4 = increasing severity]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. | Baseline (Day 1 [Week 0]) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASI Percent Change at Other Timepoints | The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale [0 = clear; 1-4 = increasing severity]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. | Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (End of Study [EOS]) | 
| Percentage of Participants With PASI 75 Response Throughout the Study | Reduction in disease was measured by PASI score. The PASI 75 response is a 75% or greater improvement (reduction in disease [PASI 75]) from baseline in PASI score. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale [0 = clear; 1-4 = increasing severity]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. | Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS) | 
| Percentage of Participants With PASI 100 Response Throughout the Study | Reduction in disease was measured by PASI score. The PASI 100 response is a 100% improvement (reduction in disease [PASI 100]) from baseline in PASI score. The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale [0 = clear; 1-4 = increasing severity]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity. | Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS) | 
| Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52 | The sPGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) used to measure the severity of disease (induration, scaling, and erythema). A sPGA response was defined as a sPGA value of clear (score 0) or almost clear (score 1). Higher scores represent worse symptom severity. | Week 12 and Week 52 (EOS) | 
| Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52 | The percentage of BSA affected was estimated by assuming that the participant's palm, excluding the fingers and thumb, represents roughly 1% of the body's surface. | Baseline (Day 1 [Week 0]), Week 12 and Week 52 (EOS) | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAEs were summarized by actual treatment received. For each category, participants were included only once, even if they experienced multiple events in that category. | Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS) | 
| Number of Participants With Events of Interests (EOIs) | The EOIs pre-specified for this study included serious systemic hypersensitivity reactions, facial palsy, pustular psoriasis, erythrodermic psoriasis, serious infections (including mycobacterial and salmonella infections), malignancy, cardiovascular events, reversible posterior leukoencephalopathy syndrome, serious depression including suicidality, and venous thromboembolism. | Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS) | 
| Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654 | A participant was considered to have developed ADAs if they: had a positive post-baseline binding or neutralizing antibody result with a negative or no result at Baseline or had a positive post-baseline binding or neutralizing antibody result with a negative or no result prior to the first dose in the post Week 28 study period. | Baseline; Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Biosimilar, Psoriasis area and severity index