Psoriasis
Conditions
Brief summary
This is a long-term, randomized, multi-center, open-label study of infliximab treatment in adults with moderate to severe plaque-type psoriasis. This study is the long-term extension of Study P04271 (NCT00251641); Study P04271 is a Phase 3b, randomized, parallel-group, multicenter, open-label, 26-week study comparing the efficacy and safety of infliximab versus methotrexate in the treatment of adult subjects with moderate to severe plaque-type psoriasis. The objectives of this study are to assess the efficacy and safety of long-term maintenance therapy versus intermittent therapy with 5 mg/kg infliximab in a moderate to severe plaque-type psoriasis population. During an interim safety evaluation of the trial, a higher incidence of serious and severe infusion reactions was observed in the intermittent treatment arm, consisting of a re-induction cycle (maximum of 4 infusions at 0, 2, 6 and 14 weeks) after a period of no treatment compared with the maintenance arm (infusions every 8 weeks without an interruption of treatment). Consequently, the sponsor has terminated the trial. The label will be updated to reflect this new information relating to the use of a re-induction regimen with infliximab.
Interventions
BIOLOGICALinfliximab
Infliximab maintenance therapy intravenous (IV) infusion every 8 weeks, 5 mg/kg body weight (first infusion at Week 4/Visit 2).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have met all inclusion/
Exclusion criteria
in Study P04271 (NCT00251641). * Subjects must have been originally randomized to infliximab in Study P04271. * Subjects must have completed the full 26 weeks of Study P04271. * Subjects must have remained on infliximab for the full 22 weeks of treatment in Study P04271. * Subjects must have achieved an improvement in Psoriasis Area and Severity Index (PASI) score \>=75% from Baseline of Study P04271 to Week 26 of Study P04271. * Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study. * Subjects are considered eligible according to the following tuberculosis (TB) criteria: * Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; * Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study medication. * Subjects' Baseline (Visit 1) clinical laboratory tests (complete blood count, blood chemistry, and urinalysis) must be within the following parameters: * Hemoglobin \>=10 g/dL * White blood cells \>=3.5 x 10\^9/L * Neutrophils \>=1.5 x 10\^9/L * Platelets \>=100 x 10\^9/L * Serum creatinine \<1.5 mg/dL (or \<133 umol/L) * Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase levels as outlined in Protocol P04563. * Total bilirubin \<2 x upper limit of normal \[Note: If Baseline laboratory tests are not yet available, then the previous laboratory tests from Week 22 of the parent study (Study P04271) should be used for enrollment. When the Baseline laboratory tests become available, the investigator must apply the above parameters to determine a subject's eligibility.\] * Subjects must be free of any clinically significant disease (other than plaque-type psoriasis or psoriatic arthritis) that would interfere with the study evaluations. * Subjects must be willing to give written informed consent and be able to adhere to dose and visit schedules. * Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must continue using such measures until 6 months after receiving the last infusion of study medication. * Female subjects of childbearing potential must have a negative urine pregnancy test at Baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128 | 128 weeks | PASI75 defined as the number of participants who achieved a \>=75% improvement in Psoriasis Area and Severity Index (PASI) from the original Baseline in Study P04271 (NCT00251641). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved PASI75 Response at Week 52 | 52 weeks | PASI75 defined as the number of participants who achieved a \>=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641) |
| Number of Participants Who Achieved PASI75 Response at Week 100 | 100 Weeks | PASI75 defined as the number of participants who achieved a \>=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641) |
| PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period) | Day 0 to 180 days | The PASI 6-month AUC is a time adjusted total PASI score over the 6 month (180 days) period. The AUC is a continuous measurement (not a score on a scale); a lower value is considered better and a higher value is considered worse. The weighted average PASI score over 6 months (using all available PASI scores during a 6 month period \[from Day 0 to 180 days\]) is obtained by using PASI 6-month AUC /180 days. |
| PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period) | Day 0 to 360 days | The PASI 12-month AUC is a time adjusted total PASI score over the 12 month (360 days) period. The AUC is a continuous measurement (not a score on a scale); and a lower value is considered better. The weighted average PASI score over 12 months (using all available PASI scores during a 12 month period \[from Day 0 to 360 days\]) is is obtained by using PASI 12-month AUC /360 days. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maintenance Infliximab Infliximab 5 mg/kg by body weight every 8 weeks | 222 |
| Intermittent Infliximab Infliximab 5 mg/kg by body weight at Weeks 0, 2, 6 and 14 following a 50% reduction in PASI from the Study P04271 (NCT00251641) Baseline | 219 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 153 | 125 |
| Overall Study | Adverse Event | 26 | 29 |
| Overall Study | Did Not Meet Protocol Eligibility | 0 | 3 |
| Overall Study | Lack of Efficacy | 20 | 23 |
| Overall Study | Lost to Follow-up | 4 | 5 |
| Overall Study | Protocol Defined Clinical Event | 0 | 1 |
| Overall Study | Protocol Violation | 6 | 9 |
| Overall Study | Withdrawal by Subject | 13 | 24 |
Baseline characteristics
| Characteristic | Maintenance Infliximab | Intermittent Infliximab | Total |
|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 12.1 | 43.3 years STANDARD_DEVIATION 12.2 | 44.5 years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 70 Participants | 63 Participants | 133 Participants |
| Sex: Female, Male Male | 152 Participants | 156 Participants | 308 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 95 / 222 | 97 / 219 |
| serious Total, serious adverse events | 24 / 222 | 23 / 219 |
Outcome results
Primary
Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128
PASI75 defined as the number of participants who achieved a \>=75% improvement in Psoriasis Area and Severity Index (PASI) from the original Baseline in Study P04271 (NCT00251641).
Time frame: 128 weeks
Population: Due to the early termination of the study, no subjects completed 128 weeks of therapy.
Secondary
Number of Participants Who Achieved PASI75 Response at Week 100
PASI75 defined as the number of participants who achieved a \>=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641)
Time frame: 100 Weeks
Population: Descriptive summary of all randomized subjects who completed 100 weeks (+ or - 4 weeks) of therapy. Based on best (minimum) PASI score at Week 100.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Infliximab | Number of Participants Who Achieved PASI75 Response at Week 100 | 18 Participants |
| Intermittent Infliximab | Number of Participants Who Achieved PASI75 Response at Week 100 | 9 Participants |
Secondary
Number of Participants Who Achieved PASI75 Response at Week 52
PASI75 defined as the number of participants who achieved a \>=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641)
Time frame: 52 weeks
Population: Descriptive summary of all randomized subjects who completed 52 weeks (+ or - 4 weeks) of therapy. Based on best (minimum) PASI score at Week 52.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maintenance Infliximab | Number of Participants Who Achieved PASI75 Response at Week 52 | 81 Participants |
| Intermittent Infliximab | Number of Participants Who Achieved PASI75 Response at Week 52 | 39 Participants |
Secondary
PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period)
The PASI 12-month AUC is a time adjusted total PASI score over the 12 month (360 days) period. The AUC is a continuous measurement (not a score on a scale); and a lower value is considered better. The weighted average PASI score over 12 months (using all available PASI scores during a 12 month period \[from Day 0 to 360 days\]) is is obtained by using PASI 12-month AUC /360 days.
Time frame: Day 0 to 360 days
Population: Participants with at least two post Study P04563 randomization PASI scores (at least one is 330 days or more from Study P04563 randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maintenance Infliximab | PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period) | 860.7 12-month PASI AUC | Standard Error 92.46 |
| Intermittent Infliximab | PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period) | 2214.2 12-month PASI AUC | Standard Error 108.5 |
Secondary
PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period)
The PASI 6-month AUC is a time adjusted total PASI score over the 6 month (180 days) period. The AUC is a continuous measurement (not a score on a scale); a lower value is considered better and a higher value is considered worse. The weighted average PASI score over 6 months (using all available PASI scores during a 6 month period \[from Day 0 to 180 days\]) is obtained by using PASI 6-month AUC /180 days.
Time frame: Day 0 to 180 days
Population: Participants with at least two post Study P04563 randomization PASI scores (at least one is 150 days or more from Study P04563 randomization).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maintenance Infliximab | PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period) | 566.2 6-month PASI AUC | Standard Error 51.22 |
| Intermittent Infliximab | PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period) | 1098.0 6-month PASI AUC | Standard Error 53.48 |