A Study of Guselkumab in Participants With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab (NAVIGATE)

• ClinicalTrials.gov Identifier: NCT02203032
• Recruitment Status: Completed
• First Posted: July 29, 2014
• Results First Posted: July 17, 2017
• Last Update Posted: September 12, 2017
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: July 25, 2014
• First Posted Date: July 29, 2014
• Results First Submitted Date: June 14, 2017
• Results First Posted Date: July 17, 2017
• Last Update Posted Date: September 12, 2017
• Actual Study Start Date: October 7, 2014
• Actual Primary Completion Date: December 25, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2017)

Number of Visits at Which Participants Achieved an Investigator's Global Assessment (IGA) Response of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) From Week 28 Through Week 40 [ Time Frame: Week 28 through Week 40 ]

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).

Original Primary Outcome Measures (submitted: July 25, 2014)

The number of visits at which participants achieve an Investigator's Global Assessment (IGA) response of 0 or 1 and at least a 2 grade improvement (from Week 16) among randomized participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 [ Time Frame: Week 28 through Week 40 ]

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 on a scale of 0 to 4 (higher score = more severe). The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).

Current Secondary Outcome Measures (submitted: June 14, 2017)

• Number of Visits at Which Participants Achieved a Psoriasis Area and Severity Index (PASI) 90 Response From Week 28 Through Week 40 [ Time Frame: Week 28 through Week 40 ]
  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.
• Number of Visits at Which Participants Achieved an IGA Score of Cleared (0) From Week 28 Through Week 40 [ Time Frame: Week 28 through Week 40 ]
  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).
• Percentage of Participants With an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) and at Least a 2 Grade Improvement (From Week 16) at Week 28 [ Time Frame: Week 28 ]
  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).

Original Secondary Outcome Measures (submitted: July 25, 2014)

• The number of visits at which participants achieve a Psoriasis Area and Severity Index (PASI) 90 response from Week 28 through Week 40 among randomized participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 [ Time Frame: Week 28 through Week 40 ]
  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 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 achieving at least a 90% improvement from baseline in the PASI score.
• The number of visits at which participants achieve an IGA response of cleared (0) from Week 28 through Week 40 among randomized participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 [ Time Frame: Week 28 through Week 40 ]
• The percentage of participants who achieve an IGA of 0 or 1 and at least a 2-grade improvement (from Week 16) at Week 28 [ Time Frame: Week 28 ]
• The number of visits at which participants achieve a PASI 100 response from Week 28 through Week 40 among randomized participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 [ Time Frame: Week 28 through Week 40 ]
  A PASI 100 response represents participants achieving 100% improvement from baseline in the PASI score.
• The number of visits at which participants achieve a PASI 75 response from Week 28 through Week 40 among randomized participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 [ Time Frame: Week 28 through Week 40 ]
  A PASI 75 response represents participants achieving at least a 75% improvement from baseline in the PASI score.
• The average percent improvement from baseline in PASI response between Week 28 and Week 40 among randomized participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 [ Time Frame: Week 28 through Week 40 ]
• The number of visits at which participants with an inadequate IGA response (IGA≥2) to ustekinumab at Week 16 who achieve a Dermatology Life Quality Index (DLQI) of 0 or 1 among randomized participants with DLQI >1 at Week 16 [ Time Frame: Week 28 through Week 40 ]
  The DLQI is a dermatology-specific quality of life instrument designed to assess the impact of the disease on a participant's quality of life. It is a 10-item PRO questionnaire that, in addition to evaluating overall quality of life, can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The DLQI produces a numeric score that can range from 0 to 30. A higher score indicates more severe disease.
• The number of visits at which participants with an inadequate IGA response (IGA≥2) to ustekinumab at Week 16 who achieve a Psoriasis Symptom and Sign Diary (PSSD) symptom score of 0 among randomized participants with a PSSD symptom score ≥1 at Week 16 [ Time Frame: Week 28 through Week 40 ]
  The PSSD is a questionnaire designed to measure the severity of psoriasis symptoms and signs over the previous 7 days for the assessment of treatment benefit. The PSSD questionnaire includes 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness and bleeding) using 0 to 10 numerical rating scales for severity. Two subscores will be derived: the psoriasis symptom score and the psoriasis sign score. A higher score indicates more severe disease.
• The number of visits at which participants with an inadequate IGA response (IGA≥2) to ustekinumab at Week 16 who achieve a PSSD sign score of 0 among randomized participants with a PSSD sign score ≥1 at Week 16 [ Time Frame: Week 28 through Week 40 ]
  See PSSD sign score described above.
• The number of visits at which participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve a score of 0 for each PSSD individual scale from Week 28 through 40 among randomized participants with PSSD scale score ≥1 at Week 16 [ Time Frame: Week 28 through Week 40 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve a PASI 90 response at Week 28 [ Time Frame: Week 28 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve an IGA of 0 or 1 and at least a 2-grade improvement (from Week 16) at Week 52 [ Time Frame: Week 52 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve a PASI 90 response at Week 52 [ Time Frame: Week 52 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve a PSSD symptom score of 0 at Week 52 among randomized participants with a PSSD symptom score ≥1 at Week 16 [ Time Frame: Week 52 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve a PSSD sign score of 0 at Week 52 among randomized participants with a PSSD sign score ≥1 at Week 16 [ Time Frame: Week 52 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve DLQI of 0 and 1 at Week 52 among randomized participants with DLQI >1 at Week 16 [ Time Frame: Week 52 ]
• The percentage of participants with an inadequate (IGA≥2) response to ustekinumab at Week 16 who achieve each PSSD individual score of 0 at Week 52 among randomized participants with PSSD scale score ≥1 at Week 16 [ Time Frame: Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Guselkumab in Participants With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Guselkumab for the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab
• Brief Summary: The purpose of this study is to evaluate the efficacy and safety of guselkumab (CNTO 1959) in the treatment of participants with moderate to severe plaque-type psoriasis (scaly skin rash) who had inadequate response to ustekinumab.
• Detailed Description: This is a randomized (assignment of study drug by chance), double-blind (participants nor study staff will know the identity of study drugs), multicenter study to evaluate efficacy and safety of guselkumab for the treatment of participants with moderate to severe plaque-type psoriasis who had an inadequate response to ustekinumab. The study will consist of a screening period, open-label and double-blind treatment periods, and a follow-up period. The treatment period will have 2 phases: an open-label treatment phase during which all participants will receive ustekinumab at Weeks 0 and 4 and a blinded treatment phase during which participants with an inadequate Investigator's Global Assessment response (IGA≥2) to ustekinumab at Week 16 will be randomized to receive either guselkumab or ustekinumab through Week 44. Participants with an IGA response of 0 or 1 (cleared or minimal disease) at Week 16 will continue to receive open-label treatment with ustekinumab every 12 weeks through Week 40. All participants will complete a follow-up phase through Week 52 for efficacy and through Week 60 for safety evaluations. The total duration of the study will be approximately 64 weeks (includes a 4-week screening period). Participants' safety will be monitored throughout the study.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Psoriasis

Intervention

• Drug: Ustekinumab
  45 mg or 90 mg given by subcutaneous injection at Weeks 0 and 4 for all participants. Participants with an IGA score of 0 or 1 at Week 16 will also receive ustekinumab every 12 weeks (q12w) from Week 16 to Week 40.
• Drug: Guselkumab
  100 mg given by subcutaneous injection at Weeks 16 and 20 and every 8 weeks (q8w) thereafter through Week 44.
• Drug: Placebo for ustekinumab
  Subcutaneous injection at Weeks 16, 28, and 40 to maintain the blind for participants randomized to treatment with guselkumab.
• Drug: Placebo for guselkumab
  Subcutaneous injection at Weeks 16 and 20 and q8w thereafter through Week 44 to maintain the blind for participants randomized to treatment with ustekinumab.

Study Arms

• Experimental: Open-label ustekinumab
  Intervention: Drug: Ustekinumab
• Experimental: Double-blind guselkumab
  Interventions:

  • Drug: Guselkumab
  • Drug: Placebo for ustekinumab
• Experimental: Double-blind ustekinumab
  Interventions:

  • Drug: Ustekinumab
  • Drug: Placebo for guselkumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 11, 2017): 872
• Original Estimated Enrollment (submitted: July 25, 2014): 800
• Actual Study Completion Date: May 24, 2016
• Actual Primary Completion Date: December 25, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of plaque-type psoriasis (with or without psoriatic arthritis for at least 6 months before the first administration of study drug
• Have a Psoriasis Area and Severity Index (PASI) greater than or equal to (>=) 12 at Screening and at Baseline
• Have an Investigator's Global Assessment (IGA) >=3 at Screening and at Baseline
• Have an involved body surface area (BSA) >= 10 percent (%) at Screening and at Baseline
• Be a candidate for phototherapy or systemic treatment for psoriasis (either naïve or history of previous treatment)

Exclusion Criteria:

• Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Has unstable cardiovascular disease, defined as a recent clinical deterioration (example [eg], unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months
• Currently has a malignancy or has a history of malignancy within 5 years before Screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration, or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study drug administration)
• Has previously received guselkumab or ustekinumab

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Germany, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02203032
• Other Study ID Numbers: CR104918; CNTO1959PSO3003 ( Other Identifier: Janssen Research & Development, LLC ); 2014-000721-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Janssen Research & Development, LLC
• Study Sponsor: Janssen Research & Development, LLC
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: August 2017