Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03998683 | A Study of Guselkumab for the Treatment of Palmoplantar-non-Pustular Psoriasis | PHASE3 | COMPLETED | 117 | — | — | Sep 3, 2019 | Nov 30, 2021 | Jan 3, 2022 | 26 | France, Germany +3 |
| NCT03818035 | A Study to Evaluate Further Therapeutic Strategies With Guselkumab in Participants With Moderate-to-Severe Plaque-Type Psoriasis | PHASE3 | COMPLETED | 880 | — | — | Feb 8, 2019 | Jan 7, 2025 | Jan 23, 2026 | 90 | France, Germany |
| NCT03451851 | A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants | PHASE3 | ACTIVE NOT_RECRUITING | 120 | — | — | Jul 11, 2018 | Dec 18, 2026 | Jun 8, 2026 | 39 | United States, Australia +7 |
| NCT03090100 | A Study to Evaluate the Comparative Efficacy of CNTO 1959 (Guselkumab) and Secukinumab for the Treatment of Moderate to Severe Plaque-type Psoriasis | PHASE3 | COMPLETED | 1,048 | — | — | Apr 27, 2017 | Sep 20, 2018 | Oct 1, 2019 | 142 | United States, Australia +7 |
| NCT02905331 | Efficacy and Safety Study of Guselkumab in the Treatment of Participants With Moderate to Severe Plaque-Type Psoriasis | PHASE3 | COMPLETED | 78 | — | — | Feb 28, 2017 | Feb 6, 2018 | Feb 4, 2025 | 14 | United States, Canada +1 |
| NCT02951533 | A Study to Compare the Efficacy of Guselkumab to Fumaric Acid Esters for the Treatment of Participants With Moderate to Severe Plaque Psoriasis | PHASE3 | COMPLETED | 119 | — | — | Dec 12, 2016 | Feb 6, 2019 | Feb 28, 2020 | 28 | Germany |
| NCT02207231 | A Study of Guselkumab in the Treatment of Participants With Moderate to Severe Plaque-Type Psoriasis | PHASE3 | COMPLETED | 837 | — | — | Nov 26, 2014 | Jun 17, 2020 | Jul 23, 2021 | 97 | United States, Australia +8 |
| NCT02207244 | A Study of Guselkumab in the Treatment of Participants With Moderate to Severe Plaque-Type Psoriasis With Randomized Withdrawal and Retreatment | PHASE3 | COMPLETED | 992 | — | — | Nov 3, 2014 | Jul 1, 2020 | Jul 22, 2021 | 93 | United States, Australia +7 |
| NCT02397382 | Pharmacokinetic Study to Evaluate the Effect of a Single Dose of Guselkumab (CNTO 1959) on CYP 450 Enzyme Activities After Subcutaneous Administration in Participants With Psoriasis | PHASE1 | COMPLETED | 16 | — | — | Jun 18, 2015 | Aug 31, 2016 | Sep 20, 2017 | 8 | United States |
Percentage of participants who achieve ppPASI75 response, defined as improvement greater than or equal to (\>=) 75 percent (%) in the ppPASI score at Week 16 will be reported. The ppPASI is an assessment tool based on the PASI that assesses erythema, pustules, desquamation and the extent of disease of the palms and/or soles.
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.
The IGA assesses participant's plaque psoriasis. Lesions were graded for induration, erythema and scaling, each using a 5 point scale. Induration: 0 = no evidence of plaque elevation, 1 = minimal plaque elevation, = 0.25 mm; 2 = mild plaque elevation, = 0.5 mm; 3 = moderate plaque elevation, = 0.75 mm; 4 = severe plaque elevation, \>1 mm; Erythema: 0 = no evidence of erythema, hyperpigmentation may be present, 1 = faint erythema, 2 = light red coloration, 3 = moderate red coloration, 4 = bright red coloration; Scaling: 0 = no evidence of scaling, 1 = minimal; occasional fine scale over less than 5% of the lesion, 2 = mild; fine scale dominates, 3 = moderate; coarse scale predominates, 4 = severe; thick, scale predominates. Final IGA score of psoriasis was based upon the average of induration, erythema and scaling scores assessed on a 5 point scale: cleared (0), minimal (1), mild (2), moderate (3), or severe (4). A higher score indicated more severe disease.
The PASI was a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body was divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas was 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 percent \[%\] to 100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 (none) to 4 (severe). The PASI produced a numeric score that can range from 0 (no visible skin involvement) to 72 (maximal skin involvement of the whole body). A higher score indicated more severe disease. A PASI 75 response represented participants who achieved at least a 75 % improvement from baseline in the PASI score.
The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score.
The IGA documents the investigator's assessment of the participants psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Participants who achieved an IGA score of cleared (0) or minimal (1) were considered IGA cleared or minimal responders. Non-responder imputation (counted as non-responders) was applied for participants who met treatment failure rules, as well as for remaining missing data after treatment failure. Participants who discontinued study drug due to lack of efficacy, an adverse event (AE) of worsening of psoriasis, or who started a protocol-prohibited medication/therapy during study that could improve psoriasis were considered as treatment failures for the study.
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 area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percent (%) to 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 can range from 0 (no psoriasis) to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score. Non-responder imputation (counted as non-responders) was applied for participants who met treatment failure rules, as well as for remaining missing data after treatment failure.
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 area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percent \[%\] to 100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 (none) to 4 (severe). The PASI produces a numeric score that can range from 0 (no visible skin involvement) to 72 (maximal skin involvement of the whole body). A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 % improvement from baseline in the PASI score.
The IGA documents the investigator's assessment of the participants' psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participants' psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).
The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents participants who achieved at least a 90 percent improvement from baseline in the PASI score.
The Cmax is the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
The Tmax is time to reach the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time.
The observed serum concentration of Guselkumab.
The frequency of anti-CNTO1959 antibodies.
| Arm | Type | Description |
|---|---|---|
| Guselkumab Group | EXPERIMENTAL | Participants will receive guselkumab 100 mg SC injections at Weeks 0, 4, 12 and placebo subcutaneous (SC) injection at Week 16 in double-blind phase followed by guselkumab 100 mg SC injections at Weeks 20, 28, 36, and 44 in open-label phase. |
| Placebo Group | PLACEBO_COMPARATOR | Participants will receive placebo SC injection at Weeks 0, 4, 12 and guselkumab 100 mg SC injection at Week 16 in double-blind phase followed by guselkumab 100 mg SC injection at Week 20, 28, 36, and 44 in open-label phase. |
| Part 1: Guselkumab | EXPERIMENTAL | Participants in group 1 (Part 1) will receive 100 milligram (mg) guselkumab subcutaneously (SC) at Weeks 0, 4, 12 and 20. |
| Part 2: Guselkumab q8w and Guselkumab q16w | EXPERIMENTAL | 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. |
| Part 2: Guselkumab q8w | EXPERIMENTAL | 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. |
| Part 3: Guselkumab Withdrawal | EXPERIMENTAL | 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. |
| Part 1 Group 1: Guselkumab | EXPERIMENTAL | Participants in Part 1a (age greater than or equal to (\>=) 12 - less than (\<) 18 years) will receive a weight-based dose of guselkumab subcutaneously (SC) at Weeks 0, 4, and 12. Participants who are PASI 90 responders at Week 16 will not receive any additional doses of guselkumab until they lose \>=50% of their Week 16 PASI response, then they receive 1 dose guselkumab, followed by a dose 4 weeks later, and every 8 weeks (q8w) thereafter through Week 52. Participants who are PASI 90 non-responders at Week 16 will receive a placebo injection at Week 16 and continue to receive guselkumab q8w from Week 20 through Week 52. Participants who are eligible and willing to continue guselkumab may enter the Long Term Extension (LTE) Phase of the study. Part 1b (age \>= 6 - \<12 years) will follow the same dosing and commence after Part 1a data review. |
| Part 1 Group 2: Placebo for Guselkumab | PLACEBO_COMPARATOR | Participants in Part 1a (age \>= 12 - \<18 years) will receive placebo for guselkumab administered SC at Weeks 0, 4, and 12. Participants who are PASI 90 responders at Week 16 will not receive any additional doses of study intervention until they lose \>=50% of their Week 16 PASI response, at which time they will receive a weight-based guselkumab SC dose, followed by a dose 4 weeks later, and q8w thereafter through Week 52. Participants who are PASI 90 non-responders at Week 16 will receive a weight-based guselkumab dose at Weeks 16 and 20, followed by q8w dosing thereafter through Week 52. Participants who are eligible and willing to continue guselkumab treatment, may enter the LTE phase of the study. Part 1b (age \>= 6 - \<12 years) will follow the same dosing and commence after Part 1a data review. |
| Part 1 Group 3: Etanercept | ACTIVE_COMPARATOR | Participants in Part 1a (age \>= 12 - \<18 years) will receive weight-based etanercept dose up to 50 milligram SC weekly through Week 15. Participants who elect to continue in the study will receive a weight-based guselkumab dose at Weeks 20 and 24, followed by q8w dosing thereafter through Week 48. Participants who are eligible and willing to continue guselkumab treatment, may enter the LTE phase of the study. Part 1b (age \>= 6 - \<12 years) will follow the same dosing and commence after Part 1a data review. |
| Part 2: Guselkumab | EXPERIMENTAL | Participants will receive a weight-based dose of open-label guselkumab SC at Weeks 0, 4 and q8w thereafter through Week 52. Participants who are eligible and willing to continue guselkumab treatment, may enter the LTE of the study and continue to receive guselkumab at Week 52 and q8w thereafter. |
| Group I: Guselkumab Plus Placebo | EXPERIMENTAL | Participants will receive 1 injection of active guselkumab and 1 injection of placebo when guselkumab is scheduled to be administered (Weeks 0, 4, 12, 20, 28, 36, and 44) or 2 injections of placebo when no guselkumab is scheduled to be administered (Weeks 1, 2, 3, 8, 16, 24, 32, and 40). Placebo injections will be administered to maintain the blind. |
| Group II: Secukinumab | ACTIVE_COMPARATOR | Participants will receive 2 injections of active secukinumab subcutaneously (SC) at Weeks 0, 1, 2, 3, 4 and every 4 weeks (q4w) thereafter through Week 44. |
| Group 1 (Guselkumab: Placebo) | EXPERIMENTAL | Participants will receive 100 milligram (mg) guselkumab administered as a 100 milligram per milliliter (mg/mL) solution in a single-use prefilled syringe (PFS) assembled in a SelfDose device at Weeks 0, 4, 12, 20, and 28; liquid placebo for guselkumab 100 mg at Week 16 to maintain the study blind. |
| Group 2 (Placebo: Guselkumab) | EXPERIMENTAL | Partcipants will receive placebo at Weeks 0, 4, and 12 followed by guselkumab 100 mg at Weeks 16, 20, and 28. |
| Group I: Guselkumab | EXPERIMENTAL | Participants will receive Guselkumab 100 milligram (mg) administered as 100 milligram per milliliter (mg/mL) solution subcutaneously (SC) by single-use prefilled syringe (PFS) at weeks 0, 4, 12 and 20. |
| Group II: Fumaric Acid Esters (FAE) | ACTIVE_COMPARATOR | Participants will receive Fumaderm initial/Fumaderm tablets by self administration at week 0. The individual FAE dose representing the optimal efficacy/tolerability ratio needs to be determined for each participant according to local prescription information. To this aim, FAE doses will be slowly increased beginning with increasing doses of Fumderm initial (containing 30 mg dimethylfumarate) over the first 3 weeks. Thereafter, participants will be switched to Fumaderm tablets (containing 120 mg dimethylfumarate) starting with 1 tablet per day. Fumaderm dose may be increased to a maximum of 3\*2 tablets per day. The decision to maintain, increase or decrease the FAE dose depends on efficacy, safety and tolerability. |
| Group I | EXPERIMENTAL | Participants received Guselkumab 100 milligram (mg) at Weeks 0, 4, and 12 and every 8 weeks (q8w) thereafter through Week 252, placebo for guselkumab at Week 16, and placebo for adalimumab (two 0.8 milliliter \[mL\] injections) at Week 0 followed by one 0.8 mL injection at Weeks 1, 3, and 5, and every 2 weeks (q2w) thereafter through Week 47. |
| Group II | PLACEBO_COMPARATOR | Participants received Placebo for guselkumab at Weeks 0, 4, and 12, and placebo for adalimumab (two 0.8 mL injections) at Week 0, followed by one 0.8 mL injection at Weeks 1, 3, and 5, and q2w through Week 15. At Week 16, placebo participants will cross over to receive guselkumab 100 mg at Weeks 16 and 20 and q8w thereafter through Week 252, as well as placebo for adalimumab at Weeks 17, 19, 21, and 23, and q2w thereafter through Week 47. |
| Group III | ACTIVE_COMPARATOR | Participants received Adalimumab 80 mg at Week 0 (two 40 mg \[0.8 mL\] injections) and 40 mg at Weeks 1, 3, 5, and q2w thereafter through Week 47, placebo for guselkumab at Weeks 0, 4, 12, 16, and 20, and q8w thereafter through Week 44 and guselkumab 100 mg at Weeks 52, 60, and q8w thereafter through Week 252. |
| Guselkumab and Cytochrome P450 Probe Cocktail | EXPERIMENTAL | Participants will be administered single dose of Guselkumab 200 milligram (mg) by subcutaneous injection (2\*100 mg) on Day 8 and Cytochrome P450 probe cocktail consist of midazolam, warfarin/vitamin K, omeprazole, dextromethorphan and caffeine orally once on Day 1,15 and 36. |
| Name | Type | Description |
|---|---|---|
| Guselkumab 100 mg | DRUG | Guselkumab 100 mg will be administered as SC injection. |
| Placebo | DRUG | Placebo will be administered as SC injection. |
| Guselkumab | DRUG | 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 Injection | DRUG | Participants of group 2b will receive matching placebo injection subcutaneously at weeks 28, 44 and 60. |
| Placebo for guselkumab | DRUG | Participants will receive a weight-based dose of placebo for guselkumab subcutaneously. |
| Etanercept | DRUG | Participants will receive a weight-based dose of etanercept (up to 50 mg) subcutaneously. |
| Secukinumab | DRUG | Participants will receive 2 injections of active secukinumab at Weeks 0, 1, 2, 3, 4 and every 4 weeks (q4w) thereafter through Week 44. |
| Fumaric Acid Esters | DRUG | Participants will receive Fumaderm initial/ Fumaderm tablets through self-administration. |
| Adalimumab | DRUG | 80 mg by subcutaneous injection at Week 0, then 40 mg at Week 1 and every 2 weeks (q2w) thereafter through Week 47. |
| Placebo for adalimumab | DRUG | Subcutaneous injections to maintain the blind. |
| Midazolam | DRUG | Midazolam will be administered orally as probe cocktail containing 0.03 mg per kilogram (kg) once on Day 1, 15 and 36. |
| Warfarin | DRUG | Warfarin will be administered orally as probe cocktail containing 10 mg once on Day 1, 15 and 36. |
| Omeprazole | DRUG | Omeprazole will be administered orally as probe cocktail containing 20 mg once on Day 1, 15 and 36. |
| Dextromethorphan | DRUG | Dextromethorphan will be administered orally as probe cocktail containing 30 mg once on Day 1, 15 and 36. |
| Caffeine | DRUG | Caffeine will be administered orally as probe cocktail containing 100 mg once on Day 1, 15 and 36. |
Inclusion Criteria: * Should have all the following: A confirmed diagnosis of moderate-to-severe palmoplantar-non-pustular psoriasis with palm and/or sole involvement and at least one plaque at a body site other than the palms and soles for at least 6 months, to confirm a diagnosis of chronic psori...