AGN-242428 in the Treatment of Plaque Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of 3 doses of AGN-242428 in adult participants with moderate to severe plaque-type psoriasis.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of AGN-242428 in Patients With Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: AGN-242428
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have a confirmed diagnosis of plaque psoriasis, diagnosed at least 6 months before study with a Physician's Global Assessment (PGA) score ≥ 3 at screening and baseline Severity of disease must be at least moderate, defined as Psoriasis Area and Severity Index (PASI) ≥ 12 and % body surface area (BSA) ≥ 10 Participant is a candidate for phototherapy or systemic therapy for psoriasis Body weight of at least 55 kilograms (kg) (121 (pound) lbs) Exclusion Criteria: Non-plaque forms of psoriasis (erythrodermic, guttate, pustular) or drug-induced psoriasis Psoriasis which has not been stable for the 4 weeks prior to screening and which is unstable at Study Day 1 History of Gilbert's, Rotor, or Dubin-Johnson syndromes or any other disorder of bilirubin metabolism History of active mycobacterium tuberculosis (TB) infection or untreated or inadequately treated latent TB Positive QuantiFERON test for TB infection at screening Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months prior to baseline Positive drug and/or alcohol test at screening (with the exception of marijuana). Retesting in the case of a positive alcohol test is allowed at the discretion of the sponsor Current treatment or history of treatment with any anti-Tumor Necrosis Factor alpha (TNFα) biologic therapy within 3 months or 5 half-lives of study, and/or all other biologics within 6 months of study (Day 1) Efficacy failure on 2 or more biologic agents for the treatment of psoriasis when the failures occurred within 1 year of the initiation of the therapy of the first biologic agent Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin (TBL) exceeding 1.5 times the upper limit of normal (ULN) at screening.

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo-matching AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. | Drug: Placebo<br>* Placebo administered as an oral capsule(s) once daily.<br>|
| Experimental: AGN-242428 Higher Dose<br>AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. | Drug: AGN-242428<br>* AGN-242428 administered as an oral capsule(s) once daily.<br>|
| Experimental: AGN-242428 Medium Dose<br>AGN-242428 capsules, oral administration, once-daily for up to 12 weeks. | Drug: AGN-242428<br>* AGN-242428 administered as an oral capsule(s) once daily.<br>|
| Experimental: AGN-242428 Lower Dose<br>AGN-242428 capsule and placebo-matching AGN-242428 capsule, oral administration, once-daily for up to 12 weeks. | Drug: AGN-242428<br>* AGN-242428 administered as an oral capsule(s) once daily.<br>Drug: Placebo<br>* Placebo administered as an oral capsule(s) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Reduction (Improvement) in Psoriasis Area and Severity Index (PASI) Score of ≥ 75% From Baseline to Week 16 | The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area. | Baseline (Day 1) to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving ≥ 2-point Reduction (Improvement) in Physician's Global Assessment (PGA) Score at Week 16 | The investigator evaluated the participant's overall severity of psoriasis using the PGA 5-point scale (0 to 4) where 0=Clear and 4=Severe. | Baseline (Day 1) to Week 16 | 
| Percentage of Participants Achieving a Clear (0) or Almost Clear (1) Score in PGA at Week 16 | The investigator evaluated the participant's overall severity of psoriasis using the PGA 5-point scale (0 to 4) where 0=Clear to 4=Severe. | Week 16 | 
| Percentage of Participants Achieving Reduction (Improvement) in PASI Score of ≥ 50% From Baseline to Week 16 | The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area. | Baseline (Day 1) to Week 16 | 
| Percentage of Participants Achieving Reduction (Improvement) in PASI Score of ≥ 90% From Baseline to Week 16 | The PASI score ranges from 0-72 (with a higher score indicating greater severity of psoriasis), based on a combination of the severity (erythema, induration, and desquamation) of psoriasis and percentage of affected area. | Baseline (Day 1) to Week 16 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. | First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose | 
| Number of Participants With TEAEs Leading to Discontinuation | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. | First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose | 
| Number of Participants With TEAEs Considered Related to the Study Treatment as Per Investigator | An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered a TEAE if the AE began or worsened (increased in severity or became serious) on or after the date of the first dose of study drug. The TEAEs related to the study drug, as assessed by Investigator are reported. | First dose of study drug to the last dose of study drug (up to Week 12) plus approximately 30 days past last dose | 
| Plasma Concentration of AGN-242428 |  | Single sample predose at Week 4 and 8 Visits, single sample 1-2 hours postdose at Weeks 6 and 10 Visits |