Clinical trial NCT00629772: Safety and Efficacy of Infliximab in Palmoplantar Psoriasis
Official title: A Double-Blind Study on the Safety and Efficacy of Infliximab in Palmoplantar Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Palmoplantar Psoriasis
Keywords: Palmoplantar psoriasis
Infliximab
Lead sponsor: Innovaderm Research Inc.
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-03-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Palmoplantar psoriasis is a variant of psoriasis affecting palms and soles. It is one of the most debilitating variants of psoriasis which very often interferes with daily activities and with the ability to work. This type of psoriasis is very difficult to treat as topicals have difficulty penetrating the thick epidermis of palms and soles and are therefore not very effective. The response to standard agents (methotrexate, cyclosporine and acitretin) is also usually limited. A number of these patients have very severe hand and feet disease with mild to no involvement elsewhere on the body.

Given the efficacy of infliximab in psoriasis, the purpose of this study is to evaluate if infliximab is safe and if it will improve severity and quality of life in patients with palmoplantar psoriasis, a debilitating variant of psoriasis.

Detailed description: A total of 24 patients with non-pustular palmoplantar psoriasis affecting at least 10% of the combined palms and soles area and with a modified palmoplantar pustulosis area severity index (m-PPPASI) of at least 8 will be recruited. Patients will be randomized (1:1) to receive either infliximab 5 mg/kg or placebo (normal saline) on weeks 0, 2 and 6. Patients assigned to placebo during the first 3 infusions will receive infliximab 5 mg/kg at weeks 14, 16 and 20 and placebo again at week 22 while patients who were assigned to receive infliximab during the first 3 infusions will receive infliximab at week 14 and placebo at week 16 and week 20 as well as infliximab for the last infusion at week 22. The primary endpoint will be at week 14. Patients will come back to the clinic at week 26 for a final efficacy and safety assessment.

Efficacy will be evaluated by assessing psoriasis plaque severity on palms and soles (physician's global assessment PGA), percentage of palms and soles area affected by psoriasis (palmoplantar surface area - PPSA) as well as m-PPPASI (modified palmoplantar pustulosis area and severity index). Quality of life will be evaluated at every visit by performing the dermatology life quality index DLQI. Safety will be evaluated by repeating chemistry and haematology laboratories at regular visits as well as by physical examinations and assessment of adverse events.

Eligibility criteria: Inclusion Criteria:

* Patient is 18 years of age or older.
* Patient has a history of palmoplantar psoriasis for at least 6 months.
* Patient has a m-PPPASI of at least 8 with at least 10% of the total surface of palms and soles affected with psoriasis at baseline
* Patients who failed either 4 weeks (or more) of treatment with a potent or superpotent topical corticosteroid, methotrexate, acitretin, cyclosporine, efalizumab, etanercept or alefacept for the treatment of palmoplantar psoriasis. Patients with a positive PPD who accept TB prophylaxis, will need to have failed 4 weeks (or more) of treatment with methotrexate, acitretin, cyclosporine, efalizumab, etanercept, alefacept or any other systemic therapies for the treatment of palmoplantar psoriasis.
* Patient with a history and/or the presence of typical plaque psoriasis outside palms and soles
* Female patient is either not of childbearing potential or is of childbearing potential and practicing an acceptable contraception
* Female patients of childbearing potential must have a negative serum pregnancy test at the Screening visit.
* Patient is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, and physical examination performed at Screening
* The investigator evaluates that the benefit / risk ratio is acceptable for the patient.
* Patients must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
* Negative PPD
* Patients with a positive PPD may be eligible if they initiate TB prophylaxis before the first injection of infliximab

Exclusion Criteria:

* Patient has a history of pustules on palms and/or soles or currently has evidence of pustules on palms and/or soles.
* Patient with Chest X Ray findings positive or suspicious for active tuberculosis.
* Patient has had opportunistic infections.
* Patient has had active TB or recent close contact with an individual with active TB.
* Patient has had a serious infection, has been hospitalized for an infection, or has been treated with intravenous (IV) antibiotics for an infection within 2 months prior to Day 0.
* Patient has had a chronic or recurrent infectious disease including hepatitis B or hepatitis C.
* Patient has a known malignancy or history of malignancy within 5-year period prior to screening (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence).
* Patient has a history of lymphoproliferative disease, has multiple sclerosis, or other central demyelinating disorder, or congestive heart failure.
* Patient has elevated aspartate aminotransferase or alanine aminotransferase levels more than twice the upper limit of normal at screening.
* Patient has received live vaccination within 3 months of randomization or plans to receive live vaccination during the study or within 3 months after the last infusion.
* Patient is pregnant, breastfeeding, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter.
* Patient has a history of an allergic reaction to infliximab or any constituent of study drug.
* Patient who has used any topical treatment for psoriasis (except non-medicated emollients) in the last 2 weeks before Day 0 with the exception of hydrocortisone and desonide for the face, groin (including genitals) and inframammary areas as well as shampoos containing tar, salicylic acid or zinc pyrithione
* Patient who has used UVB phototherapy or excessive sun exposure less than 14 days before Day 0.
* Patient has used any non-biological systemic therapy for the treatment of psoriasis (including PUVA therapy), systemic steroids or systemic immunosuppressants less than 28 days before Day 0. Investigational non-biologics agents must be discontinued at least 28 days or 5 half-lives prior to Day 0 (whichever is longer).
* Patient is currently participating in a clinical trial with an experimental drug or device.
* Patient who has used any biological therapy for the treatment of psoriasis less than 90 days before day 0.
* Patient is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed. Patients who have used oral or injectable corticosteroids less than 28 days before Day 0 are excluded.
* Patient has a poorly controlled medical condition which, in the opinion of the investigator, would put the patient at risk if the patient participated in the study.
* Patient currently uses or plans to use anti-retroviral therapy at any time during the study.
* Patient is known to have immune deficiency or is immunocompromised.
* Patient is known to be infected with the human immunodeficiency virus, hepatitis B or hepatitis C virus.
* Patient has current signs or symptoms or has a history of systemic lupus erythematosus.
* Patient has a history of clinically significant drug or alcohol abuse in the last year.
* Patient has erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis.
* Patients with a positive PPD who accept TB prophylaxis must not have any pre-existing liver disease.

Primary outcomes:
measure: 75% Improvement in Modified Palmoplantar Pustulosis Area and Severity Index (m-PPPASI) From Day 0
timeFrame: 14 weeks
Secondary outcomes:
measure: Number of Adverse Events at Week 14
timeFrame: 14 weeks
measure: Mean Dermatology Life Quality Index (DLQI) at Week 14
timeFrame: 14 weeks
measure: Mean Percent Palmoplantar Psoriasis Surface Area (PPSA) at Week 14
timeFrame: 14 weeks
measure: Mean Physician's Global Assessment (PGA) at Week 14
timeFrame: 14 weeks
measure: Mean Percent Improvement in Modified Palmoplantar Pustulosis Area and Severity Index (m-PPPASI) at Week 26
timeFrame: Baseline, 26 weeks
measure: Mean Percent Improvement in Dermatology Life Quality Index (DLQI) at Week 26
timeFrame: Baseline, 26 weeks
measure: Mean Percent Improvement in Physician's Global Assessment (PGA) at Week 26
timeFrame: Baseline, 26 weeks
measure: Mean Percent Improvement in Palmoplantar Psoriasis Surface Area (PPSA) at Week 26
timeFrame: Baseline, 26 weeks
Other outcomes:
Locations:
city: London
country: Canada
facility: The Guenther Dermatology Research Center
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc.
state: Ontario
city: Laval
country: Canada
facility: Innovaderm Research Laval
state: Quebec
city: Montreal
country: Canada
facility: Innovaderm Research
state: Quebec
city: Quebec
country: Canada
facility: Centre de recherche dermatologique du Québec Métropolitain
Study officials:
affiliation: Innovaderm Research
name: Robert Bissonnette, MD
role: PRINCIPAL_INVESTIGATOR
References: