Clinical trial NCT00408187: Randomized, Placebo and Ciclosporin Controlled Study of ISA247 in Plaque Psoriasis Patients
Official title: A Phase III, Randomized, Multicentre, Double-Blind, Placebo and Ciclosporin Controlled Study of ISA247 in Plaque Psoriasis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Keywords: Randomized Controlled Trials
Immunosuppression
Adult
Chronic Disease
Dermatologic Agents
Female
Humans
Male
Middle Aged
Severity of Illness Index
Treatment Outcome
Quality of Life
Double-Blind Method
Lead sponsor: Aurinia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2006-12-06
Enrollment: 642
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of voclosporin in patients with plaque psoriasis.

Detailed description: Psoriasis is a chronic skin condition that can have a significant impact on a patient's physical and mental well being. The most common form of psoriasis is plaque psoriasis. Targeted treatments in psoriasis have been reported recently, yet ciclosporin, a calcineurin inhibitor (CNi) remains one of the treatments which has the greatest efficacy. Voclosporin represents the possibility of a calcineurin inhibitor which is not only as efficacious as ciclosporin A, but also has an improved toxicity profile.

Eligibility criteria: Inclusion Criteria:

* Aged greater than or equal to 18 years of age inclusive at time of screening.
* Diagnosed with plaque psoriasis greater than or equal to 6 months prior to screening.
* Diagnosis of stable, plaque psoriasis; i.e. psoriasis must not be spontaneously improving or worsening in the 4 weeks prior to the screening visit.
* Psoriasis failing at least one systemic treatment regimen or where other systemic therapies are contraindicated or where tolerability is an issue.
* Plaque psoriasis involving greater than or equal to 10% of the body surface area and a SPGA score greater than or equal to 3 at screening and prior to randomization at the day 0 visit.
* Not pregnant or nursing.
* Sexually active women of childbearing potential or less than 1 year post-menopausal and sexually active men who are not surgically sterile must use a reliable form of birth control during study treatment and for at least 3 months after the last dose of study drug. Surgically sterile females are not considered to be of childbearing potential. Reliable forms of birth control include oral or depot contraceptives, and double-barrier methods.
* Written informed consent prior to washout and screening procedures.
* Able to keep study appointments and cooperate with all study requirements, in the opinion of the Investigator.

Exclusion Criteria:

* Has generalized erythrodermic, guttate, or pustular psoriasis.
* Have other dermatoses that would interfere with the evaluation of psoriasis, at the discretion of the Investigator.
* A current malignancy or history of malignancy within 5 years or a history of lymphoma at any time. Subjects can be enrolled with a history of squamous or basal cell carcinoma that has been surgically excised or removed with curettage and electrodesiccation.
* Has a current, uncontrolled bacterial, viral, or fungal infection that requires intravenous antibiotics or antifungals or has had such infections within 60 days prior to screening.
* A known history of tuberculosis.
* Serologic evidence or known latent HIV, HBV or HCV virus.
* Uncontrolled hypertension of systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 90 mmHg.
* MDRD GFR \< 60 mL/min.
* Variation between the screening and Visit 1 SCr greater than or equal to 30%.
* ALT, AST, GGT greater than or equal to 2x upper limit of normal (ULN).
* White blood cell count less than or equal to 2.8 x 10 to the ninth power/L.
* Requires the following prohibited medications or treatments during the washout or treatment period: drugs potentiating the nephrotoxicity of voclosporin, drugs interfering with its pharmacokinetics, drugs considered to contribute to psoriasis flare; or, systemic and topical psoriasis medication that may interfere with assessment of study drug efficacy.
* Has used any investigational drug or device within 30 days or 10 half lives (whichever is longer) prior to the screening visit.
* Current participation in another clinical trial of any drug or biological agent.
* Has taken biological agent(s), except flu shots, tetanus shots, or boosters, within 3 months of randomization. Biological agents include any virus, live vaccine, therapeutic serum, toxin, antitoxin, monoclonal antibodies or analogous product applicable to the prevention, treatment, or cure of diseases or injuries of man.
* Previous exposure to voclosporin.
* A history of clinically defined allergy to ciclosporin, constituents of Neoral or any of the constituents of the ISA247 formulation.
* A history of alcoholism or drug addiction.
* Weighs \< 45kg (99 lbs).
* A history of disease, including mental/emotional disorder that would interfere with the subject's participation in the study, in the evaluation of his/her response or that might cause the administration of voclosporin to pose a significant risk to the subject, in the opinion of the Investigator.

Primary outcomes:
measure: Superiority in the proportion of subjects achieving a score of "clear" or "almost clear" in the Static Physician's Global Assessment (SPGA) score
timeFrame: Twelve weeks of treatment
Secondary outcomes:
measure: To show non-inferiority of voclosporin compared to ciclosporin in the proportion of subjects achieving a score of "clear" or "almost clear" in the Static Physician's Global Assessment (SPGA) score at
timeFrame: Twelve weeks of treatment
measure: Superiority in de novo hypertriglyceridemia, defined as proportion of patients developing fasting triglycerides greater than or equal to 1.7 mmol/L
timeFrame: Twenty four weeks of treatment
measure: Superiority in de novo hypertension, defined as proportion of patients developing blood pressure greater than or equal to 140 mmHg (systolic) or greater than or equal to 90 mmHg (diastolic)
timeFrame: Twenty four weeks of treatment
measure: Superiority of renal function, defined as the proportion of patients experiencing a confirmed greater than or equal to 30% rise in serum creatinine
timeFrame: Twenty four weeks of treatment
measure: Superiority in proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI-75)
timeFrame: Twelve weeks of treatment
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Isotechnika Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: Isotechnika Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Isotechnika Investigational Site
state: British Columbia
city: St. John's
country: Canada
facility: Isotechnika Investigational Site
state: Newfoundland and Labrador
city: St. John's
country: Canada
facility: Isotechnika Investigational Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Isotechnika Investigational Site
state: Nova Scotia
city: Barrie
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: London
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Markham
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: North Bay
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Waterloo
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Ausburg
country: Germany
facility: Isotechnika Investigational Site
city: Berlin
country: Germany
facility: Isotechnika Investigational Site
city: Berlin
country: Germany
facility: Isotechnika Investigational Site
city: Berlin
country: Germany
facility: Isotechnika Investigational Site
city: Berlin
country: Germany
facility: Isotechnika Investigational Site
city: Bochum
country: Germany
facility: Isotechnika Investigational Site
city: Bochum
country: Germany
facility: Isotechnika Investigational Site
city: Dresden
country: Germany
facility: Isotechnika Investigational Site
city: Dresden
country: Germany
facility: Isotechnika Investigational Site
city: Frankfurt
country: Germany
facility: Isotechnika Investigational Site
city: Geiβen
country: Germany
facility: Isotechnika Investigational Site
city: Hamburg
country: Germany
facility: Isotechnika Investigational Site
city: Hamburg
country: Germany
facility: Isotechnika Investigational Site
city: Kiel
country: Germany
facility: Isotechnika Investigational Site
city: Leipzig
country: Germany
facility: Isotechnika Investigational Site
city: Lubeck
country: Germany
facility: Isotechnika Investigational Site
city: Mahlow
country: Germany
facility: Isotechnika Investigational Site
city: Mainz
country: Germany
facility: Isotechnika Investigational Site
city: Munster
country: Germany
facility: Isotechnika Investigational Site
city: Potsdam
country: Germany
facility: Isotechnika Investigational Site
city: Salzwedel
country: Germany
facility: Isotechnika Investigational Site
city: Wuppertal
country: Germany
facility: Isotechnika Investigational Site
city: Bialystock
country: Poland
facility: Isotechnika Investigational Site
city: Bydgoszcz
country: Poland
facility: Isotechnika Investigational Site
city: Gliwice
country: Poland
facility: Isotechnika Investigational Site
city: Iwonicz Zdroj
country: Poland
facility: Isotechnika Investigational Site
city: Krakow
country: Poland
facility: Isotechnika Investigational Site
city: Lodz
country: Poland
facility: Isotechnika Investigational Site
city: Lublin
country: Poland
facility: Isotechnika Investigational Site
city: Poznan
country: Poland
facility: Isotechnika Investigational Site
city: Szczcin
country: Poland
facility: Isotechnika Investigational Site
city: Warszawa
country: Poland
facility: Isotechnika Investigational Site
city: Warzszawa
country: Poland
facility: Isotechnika Investigational Site
city: Zabrze
country: Poland
facility: Isotechnika Investigational Site
Study officials:
affiliation: NewLab Clinical Research
name: Wayne Gulliver, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UBC
name: Vincent Ho, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: IWOLANG
name: Andrzej Langner, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universität Münster
name: Thomas A. Luger, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Akademia Medyczna
name: Slawomir Majewski, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite Universitatsmedizin Berlin
name: Wolfram Sterry, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gregory CR, Kyles AE, Bernsteen L, Wagner GS, Tarantal AF, Christe KL, Brignolo L, Spinner A, Griffey SM, Paniagua RT, Hubble RW, Borie DC, Morris RE. Compared with cyclosporine, ISATX247 significantly prolongs renal-allograft survival in a nonhuman primate model. Transplantation. 2004 Sep 15;78(5):681-5. doi: 10.1097/01.tp.0000131950.75697.71.
citation: Stalder M, Birsan T, Hubble RW, Paniagua RT, Morris RE. In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates. J Heart Lung Transplant. 2003 Dec;22(12):1343-52. doi: 10.1016/s1053-2498(03)00033-0.
citation: Abel MD, Aspeslet LJ, Freitag DG, Naicker S, Trepanier DJ, Kneteman NM, Foster RT, Yatscoff RW. ISATX247: a novel calcineurin inhibitor. J Heart Lung Transplant. 2001 Feb;20(2):161. doi: 10.1016/s1053-2498(00)00290-4. No abstract available.
citation: Bissonnette R, Papp K, Poulin Y, Lauzon G, Aspeslet L, Huizinga R, Mayo P, Foster RT, Yatscoff RW, Maksymowych WP; ISA247 Psoriasis Study Group. A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2006 Mar;54(3):472-8. doi: 10.1016/j.jaad.2005.10.061. Epub 2006 Jan 23.