Psoriasis
Conditions
Brief summary
Subjects with psoriasis will receive intravenous infliximab 5 mg/kg given over a 2-hour period at Weeks 0, 2, and 6 (induction therapy) to evaluate the efficacy of infliximab at Week 18. Subjects who achieved \>=75% improvement in Psoriasis Pustulosa Palmoplantaris Area and Severity Index (PPPASI) score at Week 8 AND had deterioration of PPPASI score of 50% from Week 8 until Week 12 were to receive an additional infusion at Week 12.
Interventions
BIOLOGICALInfliximab
Intravenous infliximab 5 mg/kg given over a 2-hour period at Weeks 0, 2, and 6 and possibly at week 12.
Sponsors
Centocor, Inc.
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 18-70 years of age at time of enrollment; male or female. * Women of childbearing potential and all men must be using adequate birth control measures and should continue using such measures until 6 months after receiving the last infusion of study agent. * Plaque-type psoriasis with evidence of mild to moderate psoriasis elsewhere or Psoriasis Pustulosa Palmo Plantaris (PPPP) of 6 months duration at least. * Adhere to study visit schedule and other protocol requirements. * Capable of giving informed consent prior to any study related procedures. * Avoid prolonged sun exposure, including tanning booths or other ultraviolet (UV) light sources during the study. * Eligible according to country-specific tuberculosis (TB) screening, eligibility assessment, and prevention rules. * Chest x-ray within 3 months prior to first infusion with no evidence of malignancy, infection, or fibrosis. * Screening laboratory test results within parameters specified in protocol.
Exclusion criteria
* Have any other form of psoriasis besides palmoplantaris and the pustular form. * Pregnant, nursing, or planning pregnancy within 6 months after last infusion. * Previous treatment with infliximab or any therapeutic agent targeted at reducing tumor-necrosis factor (TNF), including but not limited to etanercept, thalidomide, CDP870, or D2E7. * Other inflammatory disease that might confound the evaluations of benefit from the infliximab therapy, including but not limited to, rheumatoid arthritis (RA), ankylosing spondylitis, systemic lupus erythematosus, Lyme disease. * Used any investigational drug within the previous 1 month or 5 times the half life of the investigational agent, whichever is longer, or 3 months for any biologic of unknown half life. * Received any systemic medications/treatments that could affect psoriasis or PASI evaluation within 1 month prior to study. * Used topical medications/treatments that could affect psoriasis or PASI evaluation within 2 or 4 weeks of baseline visit. * Treated with any anti-CD4 antibody in the last 6 month. * Received any systemic immunosuppressive within 4 weeks prior to first infusion. * Received within 3 months prior to first infusion or are expected to receive any live virus or bacterial vaccinations during the trial or up to 3 months after the last infusion. * History of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection, recurrent urinary tract infection, or open, draining or infected skin wounds or ulcers. * Serious infection or been hospitalized or received IV antibiotics for an infection during the previous 2 months. * Have or had opportunistic infection. * Herpes zoster infection within 2 months of baseline. * Infected with human immunodeficiency virus (HIV), hepatitis B or C. * History of any clinically significant adverse events (AEs) to murine or chimeric proteins or human/murine recombinant products. * Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease. * History of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis. * Systemic lupus erythematosus. * Transplanted organ. * History of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location. * Malignancy within previous 5 years. * Concomitant diagnosis of congestive heart failure (CHF). * Unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins. * Substance abuse problem within previous 3 years. * Hypersensitivity reaction/adverse reaction to paracetamol/acetaminophen, antihistamines, topical corticosteroids. * Participation in another trial using an investigational agent or procedure during this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve at Least 75% Improvement in Palmoplantar Psoriasis Activity Severity Index (PPPASI) After 3 Infusions. | Baseline and Week 8 | The PPPASI score is an overall score of disease signs: extent, scales, erythema, erosions (fissures), induration and pustules. Extent is rated on a scale range from 0-6; all other signs are rated on a scale range from 0 to 4 in a target palm and/or sole. Total score range:0-26. A reduction in score is considered an improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieve a Moderate Response. | Baseline and Week 8 | Moderate response is defined as a 50% to 75% reduction in PPPASI score from baseline. |
| Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Weeks 12 and 18 | The Physician Static Global Assessment (PGA) documents the physician's assessment of the subject's psoriasis status according to the following categories: induration, scaling, and erythema. Each category is rated from 0 to 5, where 0 represents no evidence of induration/scaling/erythema (clear), 1 represents minimal induration/scaling/erythema, and 5 represents the most severe induration/scaling/erythema. |
| Number of Participants Who Respond to the Fourth Infusion. | Week 12 and Week 18 | \>=25% reduction in PPPASI score would be considered a response. |
| Dermatology Life Quality Index (DLQI) | Baseline and Week 12 | The DLQI is a dermatology-specific quality of life (QOL) instrument designed to assess the impact of the disease on a subject's QOL. It is a 10-item questionnaire that can be used to assess 6 different aspects that may affect QOL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The DLQI was completed by the subject prior to the PPPASI and PGA evaluations. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infliximab 5 mg/kg Intravenous infliximab 5 mg/kg given over a 2-hour period at Weeks 0, 2, and 6 and possibly at week 12. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Non-compliance | 1 |
Baseline characteristics
| Characteristic | Infliximab 5 mg/kg |
|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 23 |
| serious Total, serious adverse events | 4 / 23 |
Outcome results
Primary
Number of Participants Who Achieve at Least 75% Improvement in Palmoplantar Psoriasis Activity Severity Index (PPPASI) After 3 Infusions.
The PPPASI score is an overall score of disease signs: extent, scales, erythema, erosions (fissures), induration and pustules. Extent is rated on a scale range from 0-6; all other signs are rated on a scale range from 0 to 4 in a target palm and/or sole. Total score range:0-26. A reduction in score is considered an improvement.
Time frame: Baseline and Week 8
Population: Per Protocol population included the 17 subjects who completed the trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infliximab 5 mg/kg | Number of Participants Who Achieve at Least 75% Improvement in Palmoplantar Psoriasis Activity Severity Index (PPPASI) After 3 Infusions. | 4 participants |
Secondary
Dermatology Life Quality Index (DLQI)
The DLQI is a dermatology-specific quality of life (QOL) instrument designed to assess the impact of the disease on a subject's QOL. It is a 10-item questionnaire that can be used to assess 6 different aspects that may affect QOL: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The DLQI was completed by the subject prior to the PPPASI and PGA evaluations. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Time frame: Baseline and Week 12
Population: One of the 17 participants in the Per Protocol population did not perform the week 12 visit, therefore n=16.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infliximab 5 mg/kg | Dermatology Life Quality Index (DLQI) | Baseline | 22.6 scores on a scale | Standard Deviation 6.6 |
| Infliximab 5 mg/kg | Dermatology Life Quality Index (DLQI) | Week 12 | 12.7 scores on a scale | Standard Deviation 2.2 |
Secondary
Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18.
The Physician Static Global Assessment (PGA) documents the physician's assessment of the subject's psoriasis status according to the following categories: induration, scaling, and erythema. Each category is rated from 0 to 5, where 0 represents no evidence of induration/scaling/erythema (clear), 1 represents minimal induration/scaling/erythema, and 5 represents the most severe induration/scaling/erythema.
Time frame: Weeks 12 and 18
Population: One of the 17 participants in the Per Protocol population did not perform the week 12 visit, therefore n=16 for the Week 12 observations (but n=17 for the Week 18 observations).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infliximab 5 mg/kg | Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Induration: Week 12 | 13 participants |
| Infliximab 5 mg/kg | Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Induration: Week 18 | 13 participants |
| Infliximab 5 mg/kg | Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Erythema: Week 12 | 15 participants |
| Infliximab 5 mg/kg | Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Erythema: Week 18 | 9 participants |
| Infliximab 5 mg/kg | Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Scaling: Week 12 | 10 participants |
| Infliximab 5 mg/kg | Number of Participants Achieving Clear to Minimal PGA Score at Weeks 12 and 18. | Scaling: Week 18 | 7 participants |
Secondary
Number of Participants Who Achieve a Moderate Response.
Moderate response is defined as a 50% to 75% reduction in PPPASI score from baseline.
Time frame: Baseline and Week 8
Population: It was decided that this analysis will not be done.
Secondary
Number of Participants Who Respond to the Fourth Infusion.
\>=25% reduction in PPPASI score would be considered a response.
Time frame: Week 12 and Week 18
Population: Only three participants received a fourth infusion but according to the protocol they were not suppose to receive it at that time because their improvement in PPPASI score on Week 8 was less than 75%. Therefore, because no participants qualified to be analyzed for this endpoint, no data are given.