Arthritis, Psoriatic
Conditions
Keywords
Arthritis, Psoriatic, Ustekinumab, CNTO 1275, Stelara, Psoriasis
Brief summary
The purpose of this study is to evaluate the effectiveness (improvement of signs and symptoms) and safety of ustekinumab in participants with active psoriatic arthritis.
Detailed description
This is a randomized (participants are assigned different treatments based on chance), double-blind (neither the participant nor the physician knows whether drug or placebo is being taken, or at what dosage), parallel-group (each group of participants will be treated at the same time), and multicenter (study conducted at multiple sites) study. Approximately, 615 participants will participate in this study. Participants will be assigned to one of three treatment groups: Group I: ustekinumab 45 mg, Group II: ustekinumab 90 mg, and Group III: placebo group (an inactive substance). Participants will receive either 45 mg ustekinumab or 90 mg ustekinumab at Weeks 0, 4, and every 12 weeks until Week 88 as randomized to respective groups. Participants in placebo group will receive placebo at Weeks 0, 4, 16, and 20 and 45 mg ustekinumab at Weeks 24 and 28 followed by every 12 weeks dosing until Week 88. Participants who do not have greater than or equal to 5 percentage improvement in their disease (tender and swollen joints) will be eligible for an early escape. Specifically, during early escape at Week 16, participants in Group I will receive 90 mg ustekinumab, for participants in Group II same dosing schedule will be continued, and participants in placebo group will receive 45 mg ustekinumab. Safety evaluations will include assessments of adverse events, clinical laboratory tests, and physical examination. The maximum study duration will be approximately 108 weeks.
Interventions
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have had a documented diagnosis of psoriatic arthritis (PsA) at least 6 months * Have a diagnosis of active PsA at the time of entry into the study * If the participant is using methotrexate they should have started treatment at a dose not to exceed 25 milligram per week at least 3 months prior to the beginning of the study and should have no serious toxic side effects attributable to methotrexate. Methotrexate route of administration and doses should be stable for at least 4 weeks prior to the first administration of study agent. If currently not using methotrexate, must have not received methotrexate for at least 4 weeks prior to the first administration of the study agent
Exclusion criteria
* Have other inflammatory diseases, including but not limited to rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, or Lyme disease * Have used any therapeutic agent targeted at reducing interleukin (IL)-12 or IL-23, including but not limited to ustekinumab and briakinumab (ABT-874) * Have used any biologic agents that are targeted for reducing tumor necrosis factor-alpha, including but not limited to infliximab, etanercept, adalimumab, and golimumab * Have a medical history of latent or active granulomatous infection * Have any known malignancy or have a history of malignancy (with the exception of basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma in situ that has been treated with no evidence of recurrence, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years of the beginning of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. | Week 24 | An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 20 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 centimeters \[cm\]) 4) Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in the Disability Index Score as Measured With the Disability Index of the Health Assessment Questionnaire (HAQ-DI) | Day 1 (Baseline) and Week 24 | The HAQ-DI is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ-DI score which ranges from 0 (no disability) to 3 (completely disabled). In psoriatic arthritis, a decrease in score of 0.30 indicates clinically meaningful improvement. |
| Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 | Week 24 | The PASI is a physician-administered assessment tool used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). A PASI 75 response is defined as greater than or equal to 75 percent improvement in PASI score from baseline. |
| Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | Week 24 | An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 50 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4)Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein. |
| Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 | Week 24 | An ACR 70 response is defined as a greater than or equal to 70 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 70 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein. |
| Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002 | Day 1 (Baseline) and Week 24 | The modified vdH-S score is a radiographic evaluation of hand and feet erosions and joint space narrowing (JSN) for 20 joints per hand and 6 joints per foot with a total score ranging from 0 (best) to 528 (worst = worst possible erosion score of 320 + worst possible JSN score of 208). Higher score and positive score changes indicate more radiographic damage and radiographic progression, respectively. As per protocol, analysis for this outcome measure used pooled data from 2 studies (CNTO1275PSA3001 and PSA3002) because initial power assumptions showed that 900 participants would be required to evaluate impact of ustekinumab on structural damage (SD) progression. The 2 studies, (which had similar study designs and dosing regimens with difference to prior exposure to anti-tumor necrosis factor alpha (TNFα) therapies), were intended to independently measure efficacy in terms of signs, symptoms and physical function, while effects on SD progression is provided from an integrated analysis. |
Countries
Australia, Austria, Canada, Finland, Germany, Hungary, Latvia, Lithuania, New Zealand, Poland, Russia, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: PLACEBO Placebo Subcutaneous (SC) injections at Weeks 0, 4, 16 and 20. If Early Escape then participants would receive Ustekinumab 45 mg injections starting Week 16 with the last dose at Week 88. If Crossover then participants would receive Ustekinumab 45 milligram (mg) injections starting Week 24 with the last dose at Week 88. | 206 |
| Group 2: USTEKINUMAB 45 MG Ustekinumab Subcutaneous (SC) injections of 45 mg starting at Week 0 with the last dose at Week 88. If Early Escape then participants would receive Ustekinumab 90 mg injections starting Week 16 with the last dose at Week 88. | 205 |
| Group 3: USTEKINUMAB 90 MG Ustekinumab Subcutaneous (SC) injections of 90 mg starting at Week 0 with the last dose at Week 88. | 204 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 11 | 8 |
| Overall Study | Lack of Efficacy | 16 | 15 | 9 |
| Overall Study | Lost to Follow-up | 4 | 5 | 3 |
| Overall Study | Other | 3 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 11 | 13 |
Baseline characteristics
| Characteristic | Group 1: PLACEBO | Group 2: USTEKINUMAB 45 MG | Group 3: USTEKINUMAB 90 MG | Total |
|---|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 12.29 | 47.1 years STANDARD_DEVIATION 12.64 | 46.8 years STANDARD_DEVIATION 11.75 | 47.1 years STANDARD_DEVIATION 12.21 |
| Sex: Female, Male Female | 98 Participants | 99 Participants | 88 Participants | 285 Participants |
| Sex: Female, Male Male | 108 Participants | 106 Participants | 116 Participants | 330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 205 | 17 / 205 | 29 / 204 | 7 / 140 | 50 / 189 | 42 / 203 | 57 / 199 |
| serious Total, serious adverse events | 4 / 205 | 5 / 205 | 3 / 204 | 2 / 140 | 14 / 189 | 20 / 203 | 13 / 199 |
Outcome results
Primary
Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24.
An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 20 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 centimeters \[cm\]) 4) Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein.
Time frame: Week 24
Population: All participants randomly assigned to a treatment group were included in the efficacy analysis regardless of whether they received the assigned treatment. For early escape, data at or prior to Week 16 were carried forward through Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. | 22.8 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. | 42.4 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. | 49.5 Percentage of participants |
| All Ustekinumab Combined | Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24. | 46.0 Percentage of participants |
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
Secondary
Change From Baseline to Week 24 in the Disability Index Score as Measured With the Disability Index of the Health Assessment Questionnaire (HAQ-DI)
The HAQ-DI is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ-DI score which ranges from 0 (no disability) to 3 (completely disabled). In psoriatic arthritis, a decrease in score of 0.30 indicates clinically meaningful improvement.
Time frame: Day 1 (Baseline) and Week 24
Population: All participants randomly assigned to a treatment group were included in the efficacy analysis regardless of whether they received the assigned treatment. For early escape, data at or prior to Week 16 were carried forward through Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in the Disability Index Score as Measured With the Disability Index of the Health Assessment Questionnaire (HAQ-DI) | -0.10 Score on a scale | Standard Deviation 0.39 |
| Ustekinumab 45 mg | Change From Baseline to Week 24 in the Disability Index Score as Measured With the Disability Index of the Health Assessment Questionnaire (HAQ-DI) | -0.31 Score on a scale | Standard Deviation 0.521 |
| Ustekinumab 90 mg | Change From Baseline to Week 24 in the Disability Index Score as Measured With the Disability Index of the Health Assessment Questionnaire (HAQ-DI) | -0.40 Score on a scale | Standard Deviation 0.514 |
| All Ustekinumab Combined | Change From Baseline to Week 24 in the Disability Index Score as Measured With the Disability Index of the Health Assessment Questionnaire (HAQ-DI) | -0.36 Score on a scale | Standard Deviation 0.518 |
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
Secondary
Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002
The modified vdH-S score is a radiographic evaluation of hand and feet erosions and joint space narrowing (JSN) for 20 joints per hand and 6 joints per foot with a total score ranging from 0 (best) to 528 (worst = worst possible erosion score of 320 + worst possible JSN score of 208). Higher score and positive score changes indicate more radiographic damage and radiographic progression, respectively. As per protocol, analysis for this outcome measure used pooled data from 2 studies (CNTO1275PSA3001 and PSA3002) because initial power assumptions showed that 900 participants would be required to evaluate impact of ustekinumab on structural damage (SD) progression. The 2 studies, (which had similar study designs and dosing regimens with difference to prior exposure to anti-tumor necrosis factor alpha (TNFα) therapies), were intended to independently measure efficacy in terms of signs, symptoms and physical function, while effects on SD progression is provided from an integrated analysis.
Time frame: Day 1 (Baseline) and Week 24
Population: Analysis included: (1) combined data from studies CNTO1275PSA3001 (NCT01009086) and CNTO1275PSA3002 (NCT01077362) and (2) all participants randomly assigned to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002 | 0.97 Score on a scale | Standard Deviation 3.852 |
| Ustekinumab 45 mg | Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002 | 0.40 Score on a scale | Standard Deviation 2.11 |
| Ustekinumab 90 mg | Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002 | 0.39 Score on a scale | Standard Deviation 2.403 |
| All Ustekinumab Combined | Change From Baseline to Week 24 in Total Modified Van Der Heijde-Sharp (vdH-S) Score for the Combined Radiographic Data From Studies CNTO1275PSA3001 and CNTO1275PSA3002 | 0.40 Score on a scale | Standard Deviation 2.26 |
p-value: 0.017re-randomization test
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
Secondary
Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24
The PASI is a physician-administered assessment tool used for assessing and grading the severity of psoriatic lesions and their response to therapy. The PASI produces a numeric score that can range from 0 (no disease) to 72 (maximal disease). A PASI 75 response is defined as greater than or equal to 75 percent improvement in PASI score from baseline.
Time frame: Week 24
Population: All participants randomly assigned to a treatment group, regardless of whether they received the assigned treatment. For early escape, data at or prior to Week 16 were carried forward through Week 24. Only participants with \>=3% baseline BSA psoriatic involvement were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 | 11.0 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 | 57.2 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 | 62.4 Percentage of participants |
| All Ustekinumab Combined | Percentage of Participants (With >= 3% Baseline Body Surface Area (BSA) Psoriatic Involvement) Who Achieved a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 | 59.9 Percentage of participants |
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
Secondary
Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24
An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 50 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4)Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein.
Time frame: Week 24
Population: All participants randomly assigned to a treatment group were included in the efficacy analysis regardless of whether they received the assigned treatment. For early escape, data at or prior to Week 16 were carried forward through Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | 8.7 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | 24.9 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | 27.9 Percentage of participants |
| All Ustekinumab Combined | Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | 26.4 Percentage of participants |
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
Secondary
Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24
An ACR 70 response is defined as a greater than or equal to 70 percent improvement from baseline in swollen (66 joints) and tender (68 joints) joint counts and greater than or equal to 70 percent improvement in 3 of the following 5 assessments: 1) Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm), 2) Participant's global assessment of disease activity by VAS (0-10 cm), 3) Physician's global assessment of disease activity by VAS (0-10 cm) 4) Participant's assessment of physical function as measured by the Disability Index of the Health Assessment Questionnaire (HAQ-DI) (score of 0-3 in 8 functional areas) and 5) C reactive protein.
Time frame: Week 24
Population: All participants randomly assigned to a treatment group were included in the efficacy analysis regardless of whether they received the assigned treatment. For early escape, data at or prior to Week 16 were carried forward through Week 24.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 | 2.4 Percentage of participants |
| Ustekinumab 45 mg | Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 | 12.2 Percentage of participants |
| Ustekinumab 90 mg | Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 | 14.2 Percentage of participants |
| All Ustekinumab Combined | Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 | 13.2 Percentage of participants |
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test
p-value: <0.001re-randomization test