Clinical trial NCT00258713: A 36-Week Extension to Protocol ISA04-03
Official title: A 36-Week Extension to Protocol ISA04-03 to Evaluate the Safety and Efficacy of ISA247 in Patients With Plaque Psoriasis
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: 2005-11-28
Enrollment: 309
Sex: ALL
Minimum age (years): 18
Maximum age (years): 66
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 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 cyclosporine, 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 cyclosporine A, but also has an improved toxicity profile.

Eligibility criteria: Inclusion Criteria:

* Males and females aged 18-66 years inclusive at the time of visit 1.
* Diagnosed with plaque psoriasis ≥ 6 months.
* Currently participating in study ISA04-03 and completed the study up to and including Visit 9 of study ISA04-03.
* Not pregnant or nursing of planning to become pregnant during the course of the study
* Sexually-active women of child-bearing potential (including those who are \< 1 year postmenopausal) and sexually-active men who are practicing a highly effective method of birth control. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly and will include implants, injectables, combined oral contraceptives, double-barrier method, sexual abstinence, or a sterile partner. Sexually-active men and women of child-bearing potential should continue to practice contraception as outlined above during treatment and for ≥ 3 months after the last dose of voclosporin.
* Written informed consent prior to any study related 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 current, uncontrolled bacterial, viral, or fungal infection that requires intravenous antibiotics or antifungals.
* Has a current streptococcal infection that required oral antibiotics.
* A known history of tuberculosis.
* Serologic evidence or known latent human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) virus.
* Uncontrolled hypertension as defined as 3 readings of systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 90 mm Hg.
* MDRD GFR ≤ 60 mL/min.
* Unstable renal function (variation in GFR ≥ 30%).
* Alanine transaminase, aspartate transaminase, or gamma-glutamyl transferase ≥ 3x upper limit of normal(ULN).
* White blood cell count ≤ 2.8x10 to the ninth power/L.
* Triglycerides ≥ 3x ULN.
* Is currently taking or requires the following prohibited medications or treatments during the treatment period: drugs potentiating the nephrotoxicity of voclosporin such as chronic NSAID's or ACE inhibitors, drugs interfering with it's pharmacokinetics; drugs considered to contribute to psoriasis flare; or, systemic and topical psoriasis medication (including psoralen/ultraviolet A light treatment) that may interfere with assessment of study drug efficacy.
* Has taken biological agent(s), except flu shots, tetanus shots, or boosters, within 3 months of the start of treatment. Biological agents include any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment, or cure of diseases or injuries of man.
* A history of clinically defined allergy to cyclosporine or any of the constituents of the voclosporin formulation (vitamin E, medium chain triglyceride oil, Tween 40, ethanol).
* A history of alcoholism or drug addiction within 1 year prior to study entry.
* Weighs \< 45 kg (99 lbs) or \> 140 kg (308 lbs).
* A history of disease, including mental/emotional disorder that would interfere with the subject's participation in the study, or that might cause the administration of ISA247 to pose a significant risk to the subject, in the opinion of the investigator.

Primary outcomes:
measure: To investigate long-term safety and tolerability of voclosporin
timeFrame: Sixty weeks of continuous treatment
Secondary outcomes:
measure: To determine the proportion of subjects achieving and/or maintaining a PASI-75
timeFrame: Sixty weeks of continuous treatment
measure: To determine the proportion of subjects achieving and/or maintaining a reduction of 2 points in the SGA
timeFrame: Sixty weeks of continuous treatment
measure: To evaluate the effect of voclosporin on subject quality of life
timeFrame: Sixty weeks of continuous treatment
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Isotechnika Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: Isotechnika Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: Isotechnika Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: Isotechnika Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Isotechnika Investigational Site
state: Manitoba
city: Moncton
country: Canada
facility: Isotechnika Investigational Site
state: New Brunswick
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: Hamilton
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: London
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: London
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Maple
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Markham
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Newmarket
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: North Bay
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Oshawa
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Waterloo
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: Isotechnika Investigational Site
state: Ontario
city: Laval
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Pointe Claire
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Saint Foy
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
Study officials:
affiliation: Innovaderm Research
name: Robert Bissonnette, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Eastern Canada Cutaneous Research Associates Ltd.
name: Richard Langley, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Gilles Lauzon, PhD MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Probity Medical Research
name: Kim Papp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ventana Clinical Research Corporation
name: Neil Shear, MD
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.