Safety and Efficacy of Ustekinumab in Patients With Palmo-Plantar Pustular Psoriasis or With Palmo-Plantar Pustulosis

Condition(s) targeted: Palmo-Plantar Pustular Psoriasis; Palmo-Plantar Pustulosis

Intervention: Ustekinumab (Drug); Placebo (Soduim Chloride) (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Innovaderm Research Inc.

Official(s) and/or principal investigator(s):
Simon Nigen, MD, Principal Investigator, Affiliation: Innovaderm Research Inc.

Overall contact:
Murielle Tremoy, Sciences Master, Phone: (514) 521 4285, Ext: 238, Email: mtremoy@innovaderm.ca

This study will provide data on sasety and efficacy of Ustekinumab in patients suffering from Palmo-Plantar Pustular Psoriasis (PPPP) or Palmo-Plantar Pustulosis(PPP)

Official title: Safety and Efficacy of Ustekinumab in the Treatment of Patients With Palmo-Plantar Pustular Psoriasis or With Palmo-Plantar Pustulosis

Study design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Proportion of patients with PPPP who reach PPPASI-50 at Week 16 for patients randomized to ustekinumab as compared to patients randomized to placebo

Proportion of patients with PPP who reach PPPASI-50 at Week 16 for patients randomized to ustekinumab as compared to patients randomized to placebo.

Secondary outcome:

Evaluation of safety of ustekinumab as compared to placebo by reporting the incidence rates of adverse events and serious adverse events in patient with PPPP

Proportion of patients with PPPP who reach PPPASI-75 at Week 16 for patients randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in PPPASI at Week 16 for patients with PPPP randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in the PPPGA at Week 16 for patients with PPPP randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in PPSA at Week 16 for patients with PPPP randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in the DLQI at Week 16 for patients with PPPP randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in WPAI:PSO at Week 16 for patients with PPPP randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in PPQoLI at Week 16 for patients with PPPP randomized to ustekinumab as compared to patients randomized to placebo

Changes from baseline in PPPP at Week 28 for patients randomized to ustekinumab as measured with the PPPASI, PPPGA, PPSA, DLQI, WPAI:PSO and PPQoLI.

Detailed description: Twenty patients with active Palmo-Plantar Pustular Psoriasis (cohort A) and twenty patients with active Palmo-Plantar Pustulosis (cohort B) will be included in this placebo-controlled double-blind study. Patients in each cohort will be randomized (1: 1) to receive either ustekinumab S/C (Sub-Cutaneous) (45 mg for patients weighting 100 kg or less, and 90 mg for patients weighting more than 100 kg) or placebo.

Patients randomized to ustekinumab (10 with PPPP and 10 with PPP) will receive ustekinumab at Day 0, Weeks 4 and 16 and placebo at Week 20 whereas patients randomized to placebo (10 with PPPP and 10 with PPP) will receive placebo at Weeks 0 and 4 and ustekinumab at Weeks 16 and 20.

Patients will be seen at screening, Day 0, Weeks 4, 8, 16, 20, 24 and 28. The PPPASI (Palmo-Plantar Pustular Area and Severity Index), PPPGA (Palmo-Plantar Physician Global Assessment), PPSA (Palmo-Plantar Surface Area) will be used to evaluate severity and DLQI (Dermatology Life Quality Index), WPAI: PSO (Work Productivity and Activity Impairement Questionnaire: Psoriasis) and PPQoLI (Palmo-Plantar Quality of Life Index)will be used to evaluate quality of life. Safety will be assessed by physical examinations, evaluation of adverse events and laboratory analyses.

High quality digital medical photographs of palms and soles will be taken at Day 0, Weeks 4, 16 and 28. In addition, one optional skin biopsy from a palm or a sole will be performed at Day 0 and Week 16 and pus will be collected from pustules on palms and/or soles at Day 0 and Week 16. Finally, blood will be collected at Day 0 for genetic analysis from every patient who consents to DNA blood sampling.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Have had for at least 6 months either:

- Palmo-plantar pustular psoriasis defined as active palmo-plantar disease

morphology suggestive of psoriasis with at least one plaque of typical psoriasis outside the palms and soles or a history of typical plaque psoriasis outside the palms and soles (cohort A) OR

- Palmo-plantar pustulosis defined as active palmo-plantar morphology suggestive

of palmo-plantar pustulosis without lesions of psoriasis outside palms and soles and without a history of psoriasis (cohort B).

- PPPASI score of at least 8 on hands and/or feet and a PPPGA score of 3 (moderate) or

4 (severe) at Day 0

- Stable palmo-plantar pustular psoriasis or palmo-plantar pustulosis for the past 4

weeks

- Men or women 18 years of age or older at time of consent

- Must be candidate for phototherapy and systemic therapy

- Unless surgically sterile (or at least 1 year post-menopausal for women), or

abstinent, patient (male or female) is willing to use an effective method of contraception for at least 30 days before Day 0 and until at least 12 months after the last drug administration. Effective method of contraception are:

- Condom with spermicide, sponge with spermicide, foams with spermicide, jellies

with spermicide, diaphragm with spermicide

- Intra uterine device (IUD)

- Contraceptives (oral or parenteral)

- Nuvaring

- Vasectomy or vasectomised partner

- Surgically sterile or post-menopausal partner

- Same-sex partner

- Capable of giving informed consent and the consent must be obtained prior to any

study related procedures

- Are considered eligible according to the following TB (Tuberculosis) screening

criteria:

- Have no history of latent or active TB prior to screening Patients with latent

TB discovered at screening are not eligible for this study, even if they receive isoniazide or rifampin prophylaxis.

- No signs or symptoms suggestive of active TB upon medical history and/or

physical examination.

- No recent close contact with a person with active TB or, if there was such

contact, have a negative QuantiFERON-TB Gold test (or a negative tuberculin (less than 5mm) skin test when QuantiFERON-TB Gold is not available) and have been referred to a physician specializing in TB to undergo additional evaluation to rule out TB infection.

- Within 6 weeks prior to the first administration of study agent, have a negative

QuantiFERON-TB Gold test. For patients enrolled at sites that where QuantiFERON-TB Gold test is not available, have a negative tuberculin (less than 5mm) skin test.

- A chest radiograph (posterior-anterior as defined by site-specific

requirements), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB

- Female patients of childbearing potential have had a negative serum pregnancy test at

the screening visit

Exclusion Criteria:

- Have used topical steroids, topical tar preparations or other topical anti-psoriatic

preparations within 2 weeks preceding Day 0 except for the following which is allowed- mild to moderate potency topical corticosteroids for the face, groin, axilla, genitalia and scalp as long as they are applied with gloves: hydrocortisone, desonide, hydrocortisone valerate

- Have presence of erythrodermic or generalized pustular psoriasis

- Have presence of acute forms of tinea pedis and other causes of pustular eruptions of

palms and soles apart from PPPP or PPP based on clinical evaluation or evidence of any skin condition that would interfere with the evaluation of PPPP or PPP

- Have had, based on investigator's judgment, any significant infection within 30 days

preceding Day 0

- Have used any investigational drugs within 4 weeks of Day 0 or 5 times the half-life

of the investigational agent prior to the first administration of study agent, whichever is longer

- Have used systemic anti-psoriatic drugs such as steroids, retinoids, cyclosporine, or

methotrexate within 4 weeks of Day 0

- Have used any biologic such as alefacept, etanercept, adalimumab or infliximab within

12 weeks or 5 half-lives which ever is longer of Day 0

- Have received ultraviolet light therapy: UVB (Ultraviolet B), nbUVB (Narrow Band

Ultraviolet B), PUVA (Psoralen Ultraviolet A), or tanning bed within 4 weeks of Day 0

- Have had any severe, progressive or uncontrolled renal, hepatic, endocrine, cardiac,

gastrointestinal, pulmonary, neurologic, psychiatric, cerebral, hematologic medical condition

- Are known to be infected with hepatitis B, hepatitis C virus or Human

Immunodeficiency Virus (HIV)

- Are currently treated for latent tuberculosis

- Have or have had a serious infection (eg: sepsis, pneumonia or pyelonephritis) or

have been hospitalized or received IV (Intravenous) antibiotics for an infection during the 2 months prior to screening

- 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 prior to the first administration of study agent)

- Have received within 3 months (within 1 year for BCG (Bacillus Calmette-Guérin)

vaccination) prior to the first injection a live virus or bacterial vaccination. Patients must agree not to receive a live virus or bacterial vaccination during the trial or up to 12 months after the last study agent injection

- Have a clinically significant laboratory result that, in the opinion of the

investigator, prevents ustekinumab administration for safety reasons

- Are pregnant, nursing or planning pregnancy (both men and women) while enrolled in

the study

- Are known to have had a substance abuse (drug or alcohol) problem within the previous

12 months

- Have known hypersensitivity to ustekinumab or any of its components

Murielle Tremoy, Sciences Master, Phone: (514) 521 4285, Ext: 238, Email: mtremoy@innovaderm.ca

Kirk Barber Research, Calgary, Alberta T2S3B3, Canada; Not yet recruiting
Kirk Barber, MD, Phone: 403-299-5821, Email: kirk@kirkbarber.ca
Arjuni Seevaratnam, Phone: 403-299-5821, Email: arjuni@kirkbarber.ca
Kirk Barber, MD, Principal Investigator

Nexus Clinical Research, St John's, Newfoundland and Labrador A1A 5E8, Canada; Not yet recruiting
Ian Landells, MD, Phone: 709 726-3386
Tina Pretty-Haines, Phone: 709 726-3386
Ian DR Landells, MD, Principal Investigator
Carla Saldanha, MD, Sub-Investigator

Eastern Canada Cutaneous Research Associates Ltd, Halifax, Nova Scotia B3H 1Z4, Canada; Not yet recruiting
Richard Langley, MD, Phone: 902-423-0482, Email: richard.langley@dal.ca
Denise Teas, Phone: 902-423-0482, Email: denise.teas@hotmail.com
Richard GB Langley, MD, Principal Investigator
Alexander H Murray, MD, Sub-Investigator
Robert AW Miller, MD, Sub-Investigator
Scott J Murray, MD, Sub-Investigator

Lynderm Research, Markham, Ontario L3P 1A8, Canada; Recruiting
Charles W Lynde, MD, Phone: (905) 471-8011, Email: derma@lynderma.com
Anna Alton, Phone: (905) 471-8011, Email: research@lynderma.com
Charles W Lynde, MD, Principal Investigator
Francesca Cheung, MD, Sub-Investigator

Windsor Clinical Research Inc., Windsor, Ontario N8W 5L7, Canada; Recruiting
karen morneau, Nurse, Phone: (519) 971 7693, Email: kmorneau@bellnet.ca
Jerry Tan, MD, Principal Investigator
Lauren Yee, MD, Sub-Investigator
Michael Zajner, MD, Sub-Investigator

Innovaderm Research Inc., Montreal, Quebec H2K 4L5, Canada; Recruiting
Simon Nigen, MD, Phone: (514) 521 4285, Ext: 256, Email: snigen@innovaderm.ca
Murielle Tremoy, Sciences Master, Phone: (514) 521 4285, Ext: 238, Email: mtremoy@innovaderm.ca
Catherine Maari, MD, Sub-Investigator
Robert Bissonnette, MD, Sub-Investigator
Chantal Bolduc, MD, Sub-Investigator
Simon Nigen, MD, Principal Investigator
Pierre Lanouette, MD, Sub-Investigator

Clinique Médicale Dr Isabelle Delorme, St-Hyacinthe, Quebec J2S 6L6, Canada; Recruiting
Isabelle Delorme, MD, Phone: (450) 771 7070, Email: docteure@dreisabelledelorme.ca
Maxim Moreau, Nurse, Phone: (450) 771 7070, Email: mmoreau@dreisabelledelorme.com
Isabelle Delorme, MD, Principal Investigator

Starting date: March 2010
Last updated: April 23, 2010