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

Janssen-Cilag International NV880 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

880

Conditions

Psoriasis

Interventions

GuselkumabDRUG

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.

Placebo InjectionDRUG

Participants of group 2b will receive matching placebo injection subcutaneously at weeks 28, 44 and 60.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (90)

Outcomes

Primary Outcomes

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 percent \[%\]-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.

Time frame: Week 68

Secondary Outcomes

Groups 1 and 2c: Time to Improvement From Baseline (Week 0) in PASI Score

Time to improvement from baseline in PASI 75/90/100 response for participants with short disease duration (SDD) and longer disease duration (LDD) was reported. PASI was 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 (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 numeric score ranging from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated more severe disease. PASI responders were participants with \>=75%, \>=90%, 100% improvement in PASI respectively. For Part 2, data is reported only for those groups in which participants had PASI improvement post Week 28.

Time frame: Group 1: Week 0 up to Week 28; Group 2c: Week 28 up to Week 68

Groups 1, 2a, 2b, 2c, 3a and 3b: Percentage of Participants With Short (<=2 Years) and Longer (>2 Years) Disease Duration Who Achieved an Absolute PASI Score of 0, <=1 and <3 at Weeks 20, 28, 68, 116, 164 and 220

Data from ClinicalTrials.gov

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Hopital Prive d'Antony

Antony, France

Centre Hospitalier d'Auxerre

Auxerre, France

Polyclinique Reims Bezanne - De Courlancy

Bezanne, France

Centre Hospitalier Le Mans

Le Mans, France

Hôpital Edouard Herriot

Lyon, France

Le Bateau Blanc

Martigues, France

CHU Nantes

Nantes, France

CHU de Nice Hopital de l Archet

Nice, France

CHU Rouen

Rouen, France

HIA se Sainte-Anne - Toulon

Toulon, France

...and 80 more locations

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 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 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.

Time frame: Group 1: Weeks 20 and 28; Groups 2a, 2b, 2c: Week 68; Groups 3a and 3b: Weeks 116, 164 and 220

Group 3a and Group 3b: Percentage of Participants With Short (<=2 Years) and Longer (>2 Years) Disease Duration 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 220 for participants with short (\<= 2 years) and longer (\>2 years) disease duration was 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

Time frame: From Week 68 up to Week 220

Groups 1, 2a, 2b, 2c, 3a and 3b: Percentage of Participants Who Achieved 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.

Time frame: Group 1: Weeks 20, 28; Groups 2a, 2b, 2c: Week 68; Groups 3a, 3b: Weeks 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 220 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.

Time frame: From 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.

Time frame: Weeks 12, 16, 20 and 28

Groups 1, 2a, 2b, 2c, 3a, 3b and 3c: Change From Baseline (Week 0) in Dermatology Life Quality Index (DLQI) Score

Change from baseline (Week 0) in DLQI score were 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.

Time frame: Group 1: Baseline (Week 0), Week 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 68; Group 3a and Group 3b:Baseline (Week 0), Week 116, 164 and 220; Group 3c: Baseline (Re-Treatment [R] Week 0), Week R24

Groups 1, 2a, 2b, 2c, 3a, 3b and 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 was 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.

Time frame: Group 1: Week 28; Groups 2a, 2b, 2c: Week 68; Groups 3a and 3b: Week 116, 164 and 220; Group 3c: Week R24

Groups 1, 2a, 2b, 2c, 3a, and 3b: Percent Change From Baseline (Week 0) in Psoriasis- Affected Body Surface Area (BSA)

Percent change from baseline in the psoriasis affected BSA (%) was 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)

Time frame: Group 1: Baseline (Week 0), Week 12, 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 52 and 68, Group 3a, 3b: Baseline (Week 0), Week 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- 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 was reported. 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.

Time frame: Group 1: Baseline (Week 0), Week 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 68; Group 3a and Group 3b: Baseline (Week 0), Week 116, 164, and 220

Groups 1, 2a, 2b, 2c, 3a and 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 was 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 was defined as clinically meaningful change (response).

Time frame: Group 1: Baseline (Week 0), Week 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 68; Group 3a and Group 3b: Baseline (Week 0), Week 116, 164, and 220

Groups 2a, 2b and 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 was 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.

Time frame: Week 68

Groups 2a and 2b: Serum Trough Guselkumab Levels at Weeks 20, 28, 36 and 68

Serum trough guselkumab levels at Weeks 20, 28, 36 were analyzed. Serum samples were analyzed to determine trough concentrations of guselkumab using a validated specific, and sensitive method. Week 28 data are presented in Part 2 arms (Groups 2a and 2b) as these groups were established at Week 28, however pre-Week 28 trough concentrations are also reported under these groups to assess potential differences between Part 1 PK characteristics.

Time frame: At Weeks 20, 28, 36, 68

Groups 2d and 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 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 (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.

Time frame: Week R0 up to Week R24

Groups 1, 2a, 2b, 2c, 2d,3a, 3b, and 3c: Percentage 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.

Time frame: Group 1: From Week 0 to Week 28; Group 2a,2b 2c: From Week 28 to Week 68; Group 3a, 3b: From Week 68 to Week 220; Group 2d, 3c: From Week R0 to Week R28

Groups 1, 2a, 2b, 2c, 2d, 3a,3b and 3c: Number of Participants With Clinically Significant Laboratory Abnormalities

Number of participants with clinically significant laboratory abnormalities was reported. Data of participants with at least one lab abnormality is reported. Abnormality criteria: Aspartate Aminotransferase (AST) \>3, Alanine Aminotransferase (ALT).\>5. For arm 3a and 3b, no drug was administered, hence no laboratory data was collected, per planned analysis.

Time frame: Group 1: Week 20, Group 2a, 2b,2c: Week 68 and Group 2d and 3c: Week R28