A Study to Evaluate Further Therapeutic Strategies With Guselkumab in Participants With Moderate-to-Severe Plaque-Type Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that Super-Responders (SRe; defined as psoriasis participants who receive on-label guselkumab treatment until week 20 and respond with a Psoriasis Area and Severity Index score (PASI) = 0 at weeks 20 and 28) maintain control of disease until week 68 with prolonged treatment intervals of 16 weeks (guselkumab 100 mg every 16 weeks).

Official Title
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A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate Further Therapeutic Strategies With Guselkumab in Patients With Moderate-to-Severe Plaque-Type Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Placebo Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a disease duration of plaque psoriasis of either less than or equal to (<=2) years or (greater than (>2) years calculated from date at which first symptoms [plaque] were reported by subject to date of screening visit at screening; approximately 40 percentage (%) of participants must have a disease duration <=2 years Has moderate-to-severe plaque-psoriasis defined by a Psoriasis Area and Severity Index (PASI) score >10 or affected body surface area (BSA) >10%) and additionally a Dermatology Life Quality Index (DLQI) score >10 at baseline (week 0) Have no signs or symptoms suggestive of active tuberculosis (TB) upon medical history and/or physical examination Agrees not to receive a live virus or live bacterial vaccination during the study, or within 3 months after the last administration of study drug Agrees not to receive a Bacille Calmette-Guerin (BCG) vaccination during the study, or within 12 months after the last administration of study drug Exclusion Criteria: Has previously received any therapeutic agent directly targeted to interleukin (IL) -23 (including but not limited to guselkumab, tildrakizumab [MK3222], risankizumab [BI-655066]) Has received any systemic immunosuppressant (for example, methotrexate, azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, tacrolimus, fumaric acid esters), or anakinra within 4 weeks of the first administration of study drug. Tests positive for hepatitis B virus (HBV) infection or who are seropositive for antibodies to hepatitis C virus (HCV), unless they have 2 negative HCV RNA test results 6 months apart after completing antiviral treatment and prior to baseline and have a third negative HCV RNA test result at baseline Has received natalizumab, belimumab, or agents that modulate B cells or T cells (e.g., rituximab, alemtuzumab, abatacept, or visilizumab) within 12 months of the first administration of study drug Has received any anti - tumor necrosis factor (TNF)-α biologic therapy within 3 months before the first administration of study drug

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 |
| --- | --- |
| Experimental: Part 1: Guselkumab<br>Participants in group 1 (Part 1) will receive 100 milligram (mg) guselkumab subcutaneously (SC) at Weeks 0, 4, 12 and 20. | Drug: Guselkumab<br>* Participants will receive 100 mg guselkumab subcutaneously at Weeks 0, 4, 12 and 20 (group 1), at weeks 28, 36, 44, 52, 60 (group 2a and 2c), and at weeks 36 and 52 (group 2b). Group 2d and 3c are the re-treatment groups and will receive three injections after loss of disease control.<br>* Other names: TREMFYA;|
| Experimental: Part 2: Guselkumab q8w and Guselkumab q16w<br>Eligible participants from Part 1 will continue to participate in Part 2. Participants (super responder [SRe]) with a Psoriasis Area and Severity Index (PASI) score = 0 at weeks 20 and 28 will be randomized to guselkumab 100 mg every 8 weeks (q8w) (group 2a) or guselkumab 100 mg q16w (group 2b), at weeks 28 to 60. Group 2b will receive placebo injection at weeks 28, 44 and 60 to keep the comparison double blind. Participants losing control of disease (PASI score >5) during study Part 2 (until week 60), will enter the re-treatment arm (group 2d) and receive guselkumab 100mg q8w (at re-treatment week 0), followed by administration at re-treatment-weeks 8 and 16. | Drug: Guselkumab<br>* Participants will receive 100 mg guselkumab subcutaneously at Weeks 0, 4, 12 and 20 (group 1), at weeks 28, 36, 44, 52, 60 (group 2a and 2c), and at weeks 36 and 52 (group 2b). Group 2d and 3c are the re-treatment groups and will receive three injections after loss of disease control.<br>* Other names: TREMFYA;|
| Experimental: Part 2: Guselkumab q8w<br>Participants (Non SRe) in group 2c with a PASI score greater than (>) 0 at week 20 and/or 28 will continue to receive guselkumab 100 mg q8w until week 60. | Drug: Guselkumab<br>* Participants will receive 100 mg guselkumab subcutaneously at Weeks 0, 4, 12 and 20 (group 1), at weeks 28, 36, 44, 52, 60 (group 2a and 2c), and at weeks 36 and 52 (group 2b). Group 2d and 3c are the re-treatment groups and will receive three injections after loss of disease control.<br>* Other names: TREMFYA;Drug: Placebo Injection<br>* Participants of group 2b will receive matching placebo injection subcutaneously at weeks 28, 44 and 60.<br>|
| Experimental: Part 3: Guselkumab Withdrawal<br>Participants from groups 2a and 2b with a PASI score <3 at week 68 will be included in Part 3 (group 3a and 3b) and be withdrawn from guselkumab. Study visits will be conducted every 12 weeks until week 220 (follow-up). Participants with fluctuating disease (PASI score greater than or equal to [>=] 3) at week 68 or PASI >5 (participants losing control of disease) at any visit during part 3 after week 68 will get an opportunity to enter the re-treatment-arm (group 3c) in which participants will receive three guselkumab injections of 100 mg q8w. | Drug: Guselkumab<br>* Participants will receive 100 mg guselkumab subcutaneously at Weeks 0, 4, 12 and 20 (group 1), at weeks 28, 36, 44, 52, 60 (group 2a and 2c), and at weeks 36 and 52 (group 2b). Group 2d and 3c are the re-treatment groups and will receive three injections after loss of disease control.<br>* Other names: TREMFYA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Group 2a and Group 2b: Percentage of Participants Who Achieved an Absolute Psoriasis Area and Severity Index (PASI) Score Less Than (<) 3 at Week 68 | Percentage of participants who achieved an absolute PASI <3 at Week 68 were reported. The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the body surface area involved, which translates to a numeric score that ranged from 0 (indicated no involvement) to 6 (90 percentage [%]-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated greater severity of psoriasis. | Week 68 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Improvement From Baseline (Week 0) in PASI Score | Time to improvement from baseline in PASI (PASI 75/90/100 response and absolute PASI score =0) for participants with short disease duration (SDD) (less than or equal to [<=] 2 years) and longer disease duration (LDD) (greater than [>] 2 years) was reported. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translates to numeric score that ranged from 0 (indicated no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. PASI 75/90/100 responders were defined as participants with >= 75%, >= 90%, 100% improvement in PASI respectively. | Group 1: Week 0 up to Week 28; Group 2a, 2b, 2c: Week 28 up to Week 68 | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 3a and Group 3b: Percentage of Participants Who Achieved an Absolute PASI Score of 0, <=1 and <3 at Weeks 20, 28, 68, 116, 164 and 120 | Percentage of participants with short (<=2 years) and longer (>2 years) disease duration who achieved an absolute PASI Score of 0, <=1 and less than (<) 3 will be reported. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translated to numeric score that ranged from 0 (indicated no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. | Weeks 20, 28, 68, 116, 164 and 120 | 
| Group 3a and Group 3b: Percentage of Participants Who Retain Disease Control (Absolute PASI Score < 3) | Percentage of participants who retain disease control (that is, absolute PASI score <3 from week 68 through week 116 for participants with short (<= 2 years) and longer (>2 years) disease duration will be reported. Control of disease was defined as participants with a PASI score <3. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translated to numeric score that ranged from 0 (indicated no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease | Week 68 up to Week 116 | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 3a and Group 3b: Percentage of Participants Who Achieve a PASI 75/90/100 Response at Weeks 20, 28, 68, 116, 164, and 220 | Percentage of participants who achieved PASI 75/90/100 response were reported. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translated to numeric score that ranged from 0 (indicated no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. PASI 75 responders were defined as participants with >= 75% improvement in PASI from baseline. PASI 90 responders were defined as participants with >= 90% improvement in PASI from baseline. PASI 100 responders were defined as participants with 100% improvement in PASI from baseline. | Weeks 20, 28, 68, 116, 164, and 220 | 
| Group 3a and Group 3b: Time to Loss of Disease Control (Absolute PASI Score >5) After Treatment Withdrawal | Time to loss of disease control (absolute PASI score >5) after treatment withdrawal beyond Week 68 up to Week 116 were reported. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translated to numeric score that ranged from 0 (indicated no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. | Week 68 up to Week 220 | 
| Group 1: Percentage of Participants With an Absolute PASI Score = 0 at Weeks 12, 16, 20 and 28 | Percentage of participants with an absolute PASI score = 0 at Weeks 12, 16, 20 and 28 were reported. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translated to numeric score that ranged from 0 (indicated no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. | Weeks 12, 16, 20 and 28 | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 3a, Group 3b and Group 3c: Change From Baseline (Week 0) in Dermatology Life Quality Index (DLQI) Score at Weeks 28, 68, 116, 164 and 220 | Change from baseline (Week 0) in DLQI score at Weeks 28, 68, 116, 164 and 220 will be reported. DLQI was a 10-item instrument questionnaire designed to assess the impact of the disease on a participant's quality of life. Each question was evaluated on a 4-point scale ranged from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score ranged from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants. | Baseline (Week 0), Weeks 28, 68, 116, 164 and 220 | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 3a, Group 3b and Group 3c: Percentage of Participants Who Achieved a DLQI Score 0/1 and <5 | Percentage of participants who achieved a DLQI score 0/1 and <5 will be reported. DLQI was a 10-item instrument questionnaire designed to assess the impact of the disease on a participant's quality of life. Each question was evaluated on a 4-point scale ranged from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score ranged from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants. | Weeks 28, 68, 116, 164 and 220 | 
| Groups 1, 2a, 2b, 2c, 2d, 3a, 3b, and 3c: Percent Change From Baseline (Week 0) in Psoriasis- Affected Body Surface Area (BSA) at Weeks 12, 28, 52, 68, 80, 104, 116, 140, 164, 188, 212 and 220 | Change from baseline in the psoriasis affected BSA (%) at Weeks 12, 28, 52, 68, 80, 104, 116, 140, 164, 188, 212 and 220 will be reported. The percentage of the psoriasis-affected BSA percentage is a system used for assessing the severity of psoriasis. The plaque coverage is estimated using the rule of palm (1 palm of the hand = 1% BSA). | Baseline (Week 0), Weeks 12, 28, 52, 68, 80, 104, 116, 140, 164, 188, 212 and 220 | 
| Groups 1, 2a, 2b, 2c, 3a and 3b: Change From Baseline in Nail Assessment in Psoriasis and Psoriatic Arthritis-Quality of Life (NAPPA-QOL) at Weeks 28, 68, 116, 164 and 220 | Change from baseline in NAPPA-QOL at Weeks 28, 68, 116, 164 and 220 will be reported. The NAPPA was an instrument for assessing clinical and patient-reported outcomes in nail psoriasis. NAPPA-QOL was a 20-item nail-specific QoL questionnaire covering past week. Signs, stigma and everyday life were rated on a 5-point scale, ranged from 0 (no suffering) to 4 (high suffering). A global score was computed by averaging all items which ranged from 0 (no suffering) to 4 (high suffering). A decrease in NAPPA QoL score indicated improvement. | Baseline (Week 0), 28, 68, 116, 164 and 220 | 
| Groups 1, 2a, 2b, 2c, 3a, and 3b: Change From Baseline in Nail Assessment in Psoriasis and Psoriatic Arthritis- Patient Benefit Index (NAPPA-PBI) at Weeks 28, 68, 116, 164 and 220 | Change from baseline in NAPPA-PBI at Weeks 28, 68, 116, 164 and 220 will be reported. The NAPPA was an instrument for assessing clinical and patient-reported outcomes in nail psoriasis. NAPPA-PBI was a 24-item questionnaire to assess participant-defined needs before and participant-rated benefits after treatment. The answers were given on a scale from 0 to 4, and a global score was calculated as follows: Each benefit item was multiplied with the respective importance item, and the product is divided by the sum of all importance items. The results were summed up over all items. The resulting global score ranged from 0 (no benefit) to 4 (highest possible benefit). Higher score indicated more benefit. | Baseline (Week 0), Weeks 28, 68, 116, 164 and 220 | 
| Groups 1, 2a, 2b, 2c, 3a and 3b: Change From Baseline in Nail Assessment in Psoriasis and Psoriatic Arthritis- Clinical (NAPPA-CLIN) at Weeks 28, 68, 116, 164 and 220 | Change from baseline in NAPPA-CLIN at Weeks 28, 68, 116 164, and 220 will be reported. The NAPPA is an instrument for assessing clinical and patient-reported outcomes in nail psoriasis. NAPPA-CLIN is an instrument used by the physician to assess the least and the worst involved nail of both hands or both feet with scores ranging from 0 (no involvement) to 16 (worst involvement). A higher score indicated a worst involvement. | Baseline (Week 0), Weeks 28, 68, 116, 164 and 220 | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 3a and Group 3b: Change From Baseline (Week 0) in the Signs and Symptoms Aggregate Scores of the Psoriasis Symptoms and Signs Diary (PSSD) at Weeks 28, 68, 116, 164 and 220 | Change from baseline (Week 0) in the signs and symptoms aggregate scores of the PSSD at Weeks 28, 68, 116, 164 and 220 will be reported. The PSSD was a questionnaire designed to measure the severity of psoriasis symptoms and signs for the assessment of treatment benefit. PSSD was a participant self-administered outcomes instrument that included 11 items covering symptoms (itch, pain, stinging, burning and skin tightness) and participant observable signs (skin dryness, cracking, scaling, shedding or flaking, redness and bleeding) using 0 to 10 numerical rating scales for severity. Two sub scores each ranging from 0 to 100 were derived: the psoriasis symptom score and the psoriasis sign score. A higher score indicated more severe disease. A change of >= 40 points in PSSD symptom score or sign score, and a >= 3-point change in individual PSSD item scale scores will be defined as clinically meaningful change (response). | Baseline (Week 0), Weeks 28, 68, 116, 164 and 220 | 
| Group 2a, Group 2b and Group 2c: Percentage of Participants Who Achieved a PSSD Sign Score = 0 at Week 68 in Participants With a PSSD Sign Score >= 1 at Week 28 | Percentage of participants who achieved a PSSD sign score = 0 at Week 68 in participants with a PSSD sign score >= 1 at Week 28 will be reported. The PSSD was a questionnaire designed to measure the severity of psoriasis symptoms and signs for the assessment of treatment benefit. PSSD was a participant self-administered outcomes instrument that included 11 items covering symptoms (itch, pain, stinging, burning and skin tightness) and participant observable signs (skin dryness, cracking, scaling, shedding or flaking, redness and bleeding) using 0 to 10 numerical rating scales for severity. Two sub scores each ranging from 0 to 100 were derived: the psoriasis symptom score and the psoriasis sign score. A higher score indicated more severe disease. A change of >= 40 points in PSSD symptom score or sign score, and a >= 3-point change in individual PSSD item scale scores will be defined as clinically meaningful change (response). | Week 68 | 
| Group 1, Group 2a, Group 2b and Group 2c: Relationship Between Trough Serum Concentration and Efficacy or Serum Biomarker Level | The potential association between trough serum guselkumab concentration and efficacy or serum biomarker level will be analyzed by immunoassays. For the analyses the trough serum guselkumab concentration will be set into relation with the efficacy (e.g. PASI response) or with serum biomarker (e.g. serum IL-17A, IL-17F, IL-22) concentration. Guselkumab and all biomarker concentrations will be measured in the unit of picogram/milliliter (pg/mL). In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A higher score indicates more severe disease. | Up to Week 80 | 
| Group 2a and Group 2b: Relationship Between Trough Serum Guselkumab Levels at Weeks 20, 28, 36 and 68 and Achieving PASI Score <3 at Week 68 | The potential association between trough serum guselkumab levels at weeks 20, 28, 36 and 68 and achieving a PASI score <3 at Week 68 will be analyzed. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A higher score indicated more severe disease. | Weeks 20, 28, 36, 68 | 
| Group 2d and Group 3c: Percentage of Participants Who Were Re-Treated Due to Loss of Disease Control (PASI >5) and Regain Control of Disease (PASI <3) 24 Weeks After Start of Re-Treatment | Percentage of participants who were re-treated due to loss of disease control (PASI >5) and regain control of disease (PASI <3) 24 Weeks after start of re-treatment will be reported. PASI was a system used for assessing and grading severity of psoriatic lesions and their response to therapy. In PASI, body was divided into 4 regions: head, trunk, upper extremities, and lower extremities. Each of these areas was assessed separately for percentage of area involved, which translates to numeric score that ranged from 0 (indicates no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which were each rated on a scale of 0 to 4. PASI produced a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. | Start of re-treatment up to 24 weeks | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 2d, Group 3a, Group 3b, and Group 3c: Number of Participants With Adverse Events as a Measure of Safety and Tolerability | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. | Up to Week 220 | 
| Group 1, Group 2a, Group 2b, Group 2c, Group 2d, Group 3a, Group 3b and Group 3c): Number of Participants With Clinically Significant Laboratory Abnormalities | Number of participants with laboratory abnormalities (hematology, serum chemistry and serology) were reported. | Week 220 |