A Study to Investigate Interchangeability of 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 pharmacokinetic similarity, efficacy, safety and immunogenicity of multiple switches between ustekinumab and ABP 654 compared with continued use of ustekinumab in participants with moderate to severe plaque psoriasis.

Detailed Description
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This is a multi-center study and will enroll approximately 480 participants. After eligibility confirmation, all participants will be randomized in a 1:1 ratio into 2 treatment arms: continued use of ustekinumab or multiple switches between ustekinumab and ABP 654 at Week 28. The randomization will be stratified by prior biologic use for psoriasis (yes versus [vs] no) at baseline (Week 0), geographic region, and baseline (Week 0) body weight. All participants will receive an initial 3 doses of ustekinumab on Day 1 (Week 0), Week 4 and Week 16. At Week 28, participants will be randomized to continue on ustekinumab or switching between ABP 654 and ustekinumab every 12 weeks. At Week 28, efficacy assessments will be conducted including evaluation of Psoriasis and Area Severity Index (PASI). Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered as run-in failures and will not be randomized at Week 28; these participants will complete End of Study procedures at Week 28. The run-in period will occur from Day 1 until randomization at Week 28. Those unable to complete the Week 28 visit or did not have a PASI assessment completed at Week 28 will be discontinued from the study. The total duration of study participation for each participant will be 68 weeks, with up to 4 weeks for screening and 64 weeks after the first investigational product administration.

Official Title
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A Multicenter, Randomized, Double-blinded Study Evaluating the Pharmacokinetics, Efficacy and Safety of Multiple Switches Between Ustekinumab and ABP 654 Compared With Continued Use of Ustekinumab in Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Psoriasis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has stable moderate to severe plaque psoriasis for at least 6 months Participant has a score of PASI ≥ 12, involvement of ≥ 10% body surface area and static Physician Global Assessment ≥ 3 at screening and at baseline Participant is a candidate for phototherapy or systemic therapy Participant has previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy Female participant should have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline Participant or legally acceptable representative is capable of giving signed Institutional Review Board (IRB)/Independent Ethics Committee (IEC) informed consent Participant has no known history of latent or active tuberculosis Participant with a positive purified protein derivative (PPD) test and a history of Bacillus Calmette-Guérin (BCG) vaccination is allowed with a negative Quantiferon/T-spot test Participant with a positive PPD test or participant with a positive or indeterminate Quantiferon/T-spot test is allowed if he/she has all the following: No symptoms per tuberculosis worksheet provided by the sponsor, Amgen Inc. Documented history of adequate prophylaxis initiation prior to receiving investigational product in accordance with local recommendations No known exposure to a case of active tuberculosis after most recent prophylaxis No evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product Exclusion Criteria: Participant has erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication induced psoriasis, or other skin conditions at the time of screening (eg, eczema) that would interfere with evaluations of the effect of investigational product of psoriasis Participant has an active infection or history of infections Participant has uncontrolled, clinically significant systemic disease, such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension Participant has a mean QT internal or abnormal long QT syndrome corrected using Fridericia's formula (QTcF) of > 450 msec (for male participant) or > 470 msec (for female participant) at baseline that, in the opinion of the Investigator, is abnormal or clinically significant Participant has moderate to severe heart failure (New York Heart Associate class III/IV) Participant has known hypersensitivity to the investigational product or to any of the excipients Participant has laboratory abnormalities at screening Participant has had previous treatment with any agent specifically targeting interleukin (IL)-12 or IL-23 within 1 year prior to enrollment Participant has received biologic treatment for psoriasis within the previous month or 5 drug half-lives (whichever is longer) prior to enrollment Participant has received any investigational agents within the previous month or 5 half-lives (whichever is longer) prior to enrollment Participant has received non-biologic systemic psoriasis therapy within 4 weeks prior to enrollment Participant has received ultraviolet A phototherapy (with or without psoralen) or excimer laser within 4 weeks prior to enrollment, or ultraviolet B phototherapy within 2 weeks prior to enrollment Participant has received topical psoriasis treatment within 2 weeks prior to enrollment Participant has received other investigational procedures within 4 weeks prior to enrollment and during the course of the study Female participant is pregnant or breastfeeding or planning to become pregnant while participating in the study and for at least 5 months after the last dose of investigational product Sexually active participants and their partners who are of childbearing potential and not agreeing to use adequate protocol defined contraception methods while participating in the study and for 5 months after the last dose of investigational product

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Continued-use Group (Ustekinumab)<br>Participants will receive subcutaneous injection of ustekinumab up to Week 52. | Drug: Ustekinumab<br>* Participants will receive subcutaneous (SC) injection of ustekinumab.<br>* Other names: Stelara®;|
| Experimental: Switching Group (Ustekinumab - ABP 654)<br>Participants will initially receive injection of ustekinumab up to Week 16. Thereafter, starting from Week 28, participants will switch between ABP 654 and ustekinumab every 12 weeks up to Week 52. | Drug: Ustekinumab<br>* Participants will receive subcutaneous (SC) injection of ustekinumab.<br>* Other names: Stelara®;Drug: ABP 654<br>* Participants will receive SC injection of ABP 654.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve from Time 0 over the Dosing Interval (AUCtau) | To evaluate AUCtau in participants with multiple switches between ustekinumab and ABP 654 compared to participants receiving continued use of ustekinumab. | Week 52 (pre-dose and post-dose) until Week 64 | 
| Maximum Concentration (Cmax) | To evaluate Cmax in participants with multiple switches between ustekinumab and ABP 654 compared to participants receiving continued use of ustekinumab. | Week 52 (pre-dose and post-dose) until Week 64 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Maximum Concentration (tmax) | To assess the tmax in participants with multiple switches between ABP 654 and ustekinumab compared with participants receiving continued use of ustekinumab. | Week 52 (pre-dose and post-dose) until Week 64 | 
| Trough Concentration at Steady State (Ctrough,ss) | To assess the Ctrough,ss in participants with multiple switches between ABP 654 and ustekinumab compared with participants receiving continued use of ustekinumab. | Week 28 (pre-dose and post-dose) until Week 52 (pre-dose and post-dose) | 
| Percent Improvement in PASI From Baseline to Week 64 | 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. The higher score represents the worse symptom severity. | Baseline (Day 1) until Week 64 | 
| Percentage of Participants with PASI 75 Response at Week 64 | Reduction in disease as 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. The higher score represents the worse symptom severity. | Week 64 | 
| Percentage of Participants with PASI 100 Response at Week 64 | Reduction in disease as 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. The higher score represents the worse symptom severity. | Week 64 | 
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | To assess the safety in participants with multiple switches between ABP 654 and ustekinumab compared with participants receiving continued use of ustekinumab. | Week 28 until Week 64 | 
| Number of Participants With Events of Interest | To assess the safety in participants with multiple switches between ABP 654 and ustekinumab compared with participants receiving continued use of ustekinumab. | Week 28 until Week 64 | 
| Number of Participants With Positive Anti-drug Antibodies to ABP 654 | To assess the immunogenicity in participants with multiple switches between ABP 654 and ustekinumab compared with participants receiving continued use of ustekinumab. | Week 28 until Week 64 (Pre-dose) | 

 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, Ustekinumab, Skin Diseases, Dermatologic Agents, Papulosquamous