Clinical trial NCT00244842: Randomized Placebo-controlled Study of ISA247 in Plaque Psoriasis
Official title: A Phase III, Randomized, Multicentre, Double-Blind, Placebo-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: 2005-10-27
Enrollment: 451
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
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 which dose of voclosporin is effective in the treatment of plaque psoriasis compared to placebo.

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.

Comparison(s): Voclosporin at 3 dose levels (0.2, 0.3, and 0.4 mg/kg twice a day)compared to placebo.

Eligibility criteria: Inclusion Criteria:

* Plaque psoriasis ≥ 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.
* Plaque psoriasis involving ≥10% of the body surface area (BSA) at screening and prior to randomization at the day 0 visit.
* PASI score ≥10 at screening and prior to randomization at the day 0 visit.
* Not pregnant or nursing or planning to become pregnant during the course of the study.
* 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 current, uncontrolled bacterial, viral, or fungal infections that require intravenous antibiotics or antifungals or had had such infections within 60 days prior to screening.
* A history of streptococcal infection that required oral antibiotics within 30 days prior to screening.
* 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 by systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥ 90 mm Hg.
* MDRD GFR ≤ 60 ml/min.
* Variation between the screening and Visit 1 GFR ≥30%.
* Alanine transaminase, aspartate transaminase, or gamma-glutamyl transferase ≥ 3x upper limit of normal (ULN).
* White blood cell count ≤ 2.8 x 109/L.
* Triglycerides ≥ 3x ULN.
* Requires the following prohibited medications or treatments during the washout or treatment period: drugs potentiating the nephrotoxicity of voclosporin such as NSAID's or ACE inhibitors, drugs interfering with its 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 used any investigational drug or device within 28 days or 5 half lives (whichever is longer) prior to the screening visit.
* 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.
* Previous exposure to voclosporin.
* 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: Proportion of Subjects Achieving a PASI-75 at 12 Weeks at Each of the 3 Dose Levels of Voclosporin.
timeFrame: Twelve Weeks
Secondary outcomes:
measure: To Investigate the Safety and Tolerability of Voclosporin.
timeFrame: Twelve and twenty four weeks
measure: To Investigate the Pharmacokinetics and Pharmacodynamics of Voclosporin After Chronic Dosing in a Subset of Subjects.
timeFrame: Twelve and twenty four weeks
measure: To Evaluate the Effect of Voclosporin on Subject Quality of Life
timeFrame: Twelve and twenty four weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Isotechnika Investigational Site
state: Alberta
city: Edmonton
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: Victoria
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: 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: 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: Toronto
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: Pointe Claire
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Isotechnika Investigational Site
state: Quebec
city: Ste. Foy
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: Western Canada Dermatology Institute
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 Organization
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.
citation: Papp K, Bissonnette R, Rosoph L, Wasel N, Lynde CW, Searles G, Shear NH, Huizinga RB, Maksymowych WP. Efficacy of ISA247 in plaque psoriasis: a randomised, multicentre, double-blind, placebo-controlled phase III study. Lancet. 2008 Apr 19;371(9621):1337-42. doi: 10.1016/S0140-6736(08)60593-0.