A Phase 2b Study of Baricitinib in Participants With Moderate to Severe Psoriasis

Study Overview
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Brief Summary
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This is a dose-ranging study designed to investigate the efficacy and safety of Baricitinib in the treatment of participants with moderate to severe, chronic plaque psoriasis as assessed by the Psoriasis Area and Severity Index (PASI) score and routine safety assessments.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Phase 2b Study of Baricitinib in Patients With Moderate-to-Severe Plaque Psoriasis

Conditions
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Psoriasis, Skin Diseases, Skin Diseases, Papulosquamous

Intervention / Treatment
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* Drug: Placebo
* Drug: Baricitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: You must have active chronic plaque psoriasis for at least 6 months prior to entry into the study You are a candidate for systemic therapy and/or phototherapy You must have active plaque psoriasis covering at least 12% body surface area You must have Psoriasis Area and Severity Index (PASI) score of at least 12 You must have Static Physician's Global Assessment (sPGA) score of at least 3 Exclusion Criteria: You must not have received a biologic agent/monoclonal antibody within 8 weeks prior to entry into the study You must not have prior treatment with an oral Janus kinase (JAK) inhibitor You must not have received a systemic psoriasis (Ps) therapy within 4 weeks prior to entry into the study You must not have received a phototherapy within 4 weeks prior to entry into the study You must not have received a topical Ps therapy with psoralens within 4 weeks prior to entry into the study You must not be pregnant or nursing If female of childbearing potential or a male, and do not agree to use 2 forms of highly effective methods of birth control for at least 28 days following the last dose of investigational product You must not have had symptomatic herpes zoster or herpes simplex infection within 12 weeks or have a history of disseminated/complicated herpes zoster You must not have evidence of active infection, such as fever ≥38.0ºC (100.4ºF) You must not have a history of active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) You must not be immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study You must not have known history hypogammaglobulinemia You must not have had a serious systemic or local infection within 12 weeks prior to entry into the study You must not have been exposed to a live vaccine within 12 weeks prior to entry into the study, or expected to need/receive a live vaccine (including herpes zoster vaccination) during the course of the study You must not have had household contact with a person with active tuberculosis (TB) and did not receive appropriate and documented prophylaxis for TB You must not have a serious and/or unstable illness that, in the opinion of the investigator, poses an unacceptable risk for the your participation in the study You must not have or have had a history of lymphoproliferative disease; or signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or active primary or recurrent malignant disease; or been in remission from clinically significant malignancy for less than 5 years You must not have a history of chronic alcohol abuse or intravenous (IV) drug abuse within the last 2 years You must not have donated blood of more than 500 mL within 4 weeks You must not have received a topical Ps treatment within 2 weeks prior to entry into the study Exceptions: class 6 (mild, such as desonide) or class 7 (least potent, such as hydrocortisone) topical steroids used on the face, axilla, palms, soles, and/or genitalia non-medicated shampoos (for example, that do not contain corticosteroids, coal tar, or vitamin D3 analogues) emollients that do not contain alpha or beta hydroxyl acids

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Part A: Placebo administered orally (PO) once daily (QD) for 12 weeks. Part B: Placebo participants stayed on placebo or re-randomized to baricitinib 8 milligram (mg) or 10 mg PO QD for 12 weeks. Part C: Baricitinib participants re-randomized to 4 mg or placebo PO QD for 16 weeks. Part D: Retreated with Part B efficacious dose. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: Baricitinib 2 mg<br>Part A: Baricitinib administered PO QD for initial 12 weeks. Part B: Depending on participant's response, participant was maintained on current dose, or re-randomized to increased dose PO QD for 12 weeks. Part C: Participants re-randomized to half dose or placebo PO QD for 16 weeks. Part D: Participants retreated with Part B efficacious dose for 52 weeks. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB028050;|
| Experimental: Baricitinib 4 mg<br>Part A: Baricitinib administered PO QD for initial 12 weeks. Part B: Depending on participant's response, participant was maintained on current dose, or re-randomized to increased dose PO QD for 12 weeks. Part C: Participants re-randomized to half dose or placebo PO QD for 16 weeks. Part D: Participants retreated with Part B efficacious dose for 52 weeks. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB028050;|
| Experimental: Baricitinib 8 mg<br>Part A: Baricitinib administered PO QD for initial 12 weeks. Part B: Depending on participant's response, participant was maintained on current dose, or re-randomized to increased dose PO QD for 12 weeks. Part C: Participants re-randomized to half dose or placebo PO QD for 16 weeks. Part D: Participants retreated with Part B efficacious dose for 52 weeks. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB028050;|
| Experimental: Baricitinib 10 mg<br>Part A: Baricitinib administered PO QD for initial 12 weeks. Part B: Depending on participant's response, participant was maintained on current dose, or discontinued from the study for 12 weeks. Part C: Participants re-randomized to 4mg dose or placebo PO QD for 16 weeks. Part D: Participants retreated with Part B efficacious dose for 52 weeks. | Drug: Baricitinib<br>* Administered orally<br>* Other names: INCB028050;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Psoriasis Area and Severity Index Score ≥75% (PASI 75) Improvement (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis. Measure: Psoriasis Area and Severity Index [PASI]) | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation (scaling), erythema (redness), and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) of (0, 1) (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis. Measure: Static Physician Global Assessment [sPGA]) | The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline in sPGA score. | Week 12 | 
| Percentage of Participants Achieving an sPGA of (0, 1) (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis. Measure: Static Physician Global Assessment [sPGA]) | The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline in sPGA score. | Week 24 | 
| Percentage of Participants Achieving an sPGA of (0, 1) (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis. Measure: Static Physician Global Assessment [sPGA]) | The sPGA is a physician's determination of the participant's psoriasis lesions overall at a given time point categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), severe (4), or very severe (5). An sPGA (0,1) response was defined as a post-baseline sPGA score of 0 or 1 with at least a 2-point improvement from baseline in sPGA score. | Week 92 | 
| Change From Baseline in Part A in Mean Psoriasis Area and Severity Index (PASI) Total Score to Week 12 (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis. Measure: Psoriasis Area and Severity Index [PASI]) | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. Least Squares Means (LS Means) were calculated using an analysis of covariance (ANCOVA) model on the last observation carried forward (LOCF) with treatment group as a fixed effect and baseline PASI score as a continuous covariate. | Baseline Part A, Week 12 | 
| Change From Baseline in Part A in Mean Psoriasis Area and Severity Index (PASI) Total Score to Week 24 (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis: Measure: Psoriasis Area and Severity Index [PASI]) | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. | Baseline Part A, Week 24 | 
| Change From Baseline in Part D in Mean Psoriasis Area and Severity Index (PASI) Total Score to Week 92 (Efficacy of Baricitinib in Participants With Moderate to Severe Plaque Psoriasis. Measure: Psoriasis Area and Severity Index [PASI]) | The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no Ps to 72 for the most severe disease. | Baseline Part D, Week 92 | 
| Change From Baseline Part A in Dermatology Life Quality Index (DLQI) Total Score to Week 12 | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. Least Square (LS) Means in total DLQI score were calculated using Mixed Model Repeated Measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. | Baseline Part A, Week 12 | 
| Change From Baseline Part A in Dermatology Life Quality Index (DLQI) Total Score to Week 24 | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. | Baseline Part A, Week 24 | 
| Change From Baseline Part D in Dermatology Life Quality Index (DLQI) Total Score to Week 92 | The DLQI is a simple, participant-administered, 10 question, validated, quality-of-life questionnaire that covers 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include not at all, a lot, and very much, with corresponding scores of 1, 2, and 3, respectively, and unanswered (not relevant) responses scored as 0. Totals range from 0 to 30 (less to more impairment), and a 5 point change from baseline is considered clinically relevant. | Baseline Part D, Week 92 | 
| Change From Baseline Part A in Itch Numeric Rating Scale (Itch NRS) Score at Week 12 | The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours. LS Means were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. | Baseline Part A, Week 12 | 
| Change From Baseline Part A in Itch Numeric Rating Scale (Itch NRS) Score to Week 24 | The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours. | Baseline Part A, Week 24 | 
| Change From Baseline Part D in Itch Numeric Rating Scale (Itch NRS) Score to Week 92 | The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching from Ps is indicated by circling the number that best describes the worst level of itching in the past 24 hours. | Baseline Part D, Week 92 | 
| Change From Baseline Part A in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score at Week 12 | The 16-item QIDS-SR16 version is a widely used validated scale designed to assess the severity of depressive symptoms. The participant was asked to rate the severity and frequency of specific symptoms present over the last 7 days. The QIDS-SR16 total scores range from 0 to 27, where higher scores indicate higher severity of symptoms. LS Means were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. | Baseline Part A, Week 12 | 
| Change From Baseline Part A in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score to Week 24 | The QIDS-SR16 is a 16-item, self-report instrument intended to assess the existence and severity of symptoms of depression as listed in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) (APA 1994). A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 to 3. The 16 items corresponding to 9 depression domains are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. The domains assessed by the instrument include: (1) sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, (5) interest, (6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or hypersomnia), (8) decrease/increase in appetite/weight, and (9) psychomotor agitation/retardation. | Baseline Part A, Week 24 | 
| Change From Baseline Part D in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score to Week 92 | The QIDS-SR16 is a 16-item, self-report instrument intended to assess the existence and severity of symptoms of depression as listed in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) (APA 1994). A participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 to 3. The 16 items corresponding to 9 depression domains are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. The domains assessed by the instrument include: (1) sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, (5) interest, (6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or hypersomnia), (8) decrease/increase in appetite/weight, and (9) psychomotor agitation/retardation. | Baseline Part D, Week 92 | 
| Change From Baseline Part A in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Scores | The EQ-5D-5L is a standardized measure of health status of the participant. One of two portions of the EQ-5D-5L was used in which a self-perceived health score is assessed using a visual analogue scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine. This information is used as a quantitative measure of health outcome. LS Means were calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects. | Baseline Part A, Week 12 | 
| Change From Baseline Part A in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Scores | The EQ-5D-5L is a standardized measure of health status of the participant. One of two portions of the EQ-5D-5L was used in which a self-perceived health score is assessed using a visual analogue scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine. This information is used as a quantitative measure of health outcome. | Baseline Part A, Week 24 | 
| Change From Baseline Part D in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Scores | The EQ-5D-5L is a standardized measure of health status of the participant. One of two portions of the EQ-5D-5L was used in which a self-perceived health score is assessed using a visual analogue scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 mm indicated the worst health you can imagine and 100 mm indicated the best health you can imagine. This information is used as a quantitative measure of health outcome. | Baseline Part D, Week 92 | 
| Percentage of Participants Experiencing Rebound Upon Discontinuation of Study Drug in Part C | Rebound was defined as worsening of psoriasis compared to baseline at Week 0 (for example, PASI score >125% of baseline value) or new pustular, erythrodermic, or more inflammatory psoriasis occurring within 3 months of stopping study drug. | Week 40 | 
| Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib |  | Day 1:15 minutes(m) to 30m and 1hour(h) to 3h Postdose; Week 1:Predose; Week 4:Predose; Week 8:Predose; 15m to 30m and 1h to 3h Postdose, Week 12:Predose; Weeks 14 and 20; Week 24:Predose; Week 28; Week 40. If applicable: Weeks 4, 24, and 52 Post-Relapse | 
| PK: Area Under the Concentration-Time Curve Versus Time During One Dosing Interval at Steady State (AUC τ,ss) |  | Day 1:15 minutes(m) to 30m and 1hour(h) to 3h Postdose; Week 1:Predose; Week 4:Predose; Week 8:Predose; 15m to 30m and 1h to 3h Postdose, Week 12:Predose; Weeks 14 and 20; Week 24:Predose; Week 28; Week 40. If applicable: Weeks 4, 24, and 52 Post-Relapse | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe, Plaque, Chronic, Moderate