Randomized, Placebo and Ciclosporin Controlled Study of ISA247 in Plaque Psoriasis Patients

Psoriasis Clinical Trial

— ESSENCE  

Official title:

A Phase III, Randomized, Multicentre, Double-Blind, Placebo and Ciclosporin Controlled Study of ISA247 in Plaque Psoriasis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00408187
• Other study ID #: ISA05-25
• Status: Completed
• Phase: Phase 3
• First received: December 4, 2006
• Last updated: July 29, 2009
• Start date: December 2006
• Est. completion date: December 2008

Study information

• Verified date: July 2009
• Source: Aurinia Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 642
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• voclosporin
voclosporin 0.4 mg/kg po BID
• Ciclosporin
ciclosporin 1.5 mg/kg po BID
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	Isotechnika Investigational Site	Barrie	Ontario
Canada	Isotechnika Investigational Site	Edmonton	Alberta
Canada	Isotechnika Investigational Site	Halifax	Nova Scotia
Canada	Isotechnika Investigational Site	London	Ontario
Canada	Isotechnika Investigational Site	Markham	Ontario
Canada	Isotechnika Investigational Site	Montreal	Quebec
Canada	Isotechnika Investigational Site	Montreal	Quebec
Canada	Isotechnika Investigational Site	North Bay	Ontario
Canada	Isotechnika Investigational Site	Ottawa	Ontario
Canada	Isotechnika Investigational Site	Quebec City	Quebec
Canada	Isotechnika Investigational Site	St. John's	Newfoundland and Labrador
Canada	Isotechnika Investigational Site	St. John's	Newfoundland and Labrador
Canada	Isotechnika Investigational Site	Surrey	British Columbia
Canada	Isotechnika Investigational Site	Vancouver	British Columbia
Canada	Isotechnika Investigational Site	Waterloo	Ontario
Germany	Isotechnika Investigational Site	Ausburg
Germany	Isotechnika Investigational Site	Berlin
Germany	Isotechnika Investigational Site	Berlin
Germany	Isotechnika Investigational Site	Berlin
Germany	Isotechnika Investigational Site	Berlin
Germany	Isotechnika Investigational Site	Bochum
Germany	Isotechnika Investigational Site	Bochum
Germany	Isotechnika Investigational Site	Dresden
Germany	Isotechnika Investigational Site	Dresden
Germany	Isotechnika Investigational Site	Frankfurt
Germany	Isotechnika Investigational Site	Geißen
Germany	Isotechnika Investigational Site	Hamburg
Germany	Isotechnika Investigational Site	Hamburg
Germany	Isotechnika Investigational Site	Kiel
Germany	Isotechnika Investigational Site	Leipzig
Germany	Isotechnika Investigational Site	Lubeck
Germany	Isotechnika Investigational Site	Mahlow
Germany	Isotechnika Investigational Site	Mainz
Germany	Isotechnika Investigational Site	Munster
Germany	Isotechnika Investigational Site	Potsdam
Germany	Isotechnika Investigational Site	Salzwedel
Germany	Isotechnika Investigational Site	Wuppertal
Poland	Isotechnika Investigational Site	Bialystock
Poland	Isotechnika Investigational Site	Bydgoszcz
Poland	Isotechnika Investigational Site	Gliwice
Poland	Isotechnika Investigational Site	Iwonicz Zdroj
Poland	Isotechnika Investigational Site	Krakow
Poland	Isotechnika Investigational Site	Lodz
Poland	Isotechnika Investigational Site	Lublin
Poland	Isotechnika Investigational Site	Poznan
Poland	Isotechnika Investigational Site	Szczcin
Poland	Isotechnika Investigational Site	Warszawa
Poland	Isotechnika Investigational Site	Warzszawa
Poland	Isotechnika Investigational Site	Zabrze

Sponsors (1)

Lead Sponsor	Collaborator
Aurinia Pharmaceuticals Inc.

Countries where clinical trial is conducted

Canada,  Germany,  Poland, 

References & Publications (4)

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. — View 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. Epub 2006 Jan 23. — View 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. — View Citation

Stalder M, Bîrsan 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Superiority in the proportion of subjects achieving a score of "clear" or "almost clear" in the Static Physician's Global Assessment (SPGA) score		Twelve weeks of treatment	No
Secondary	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		Twelve weeks of treatment	No
Secondary	Superiority in de novo hypertriglyceridemia, defined as proportion of patients developing fasting triglycerides greater than or equal to 1.7 mmol/L		Twenty four weeks of treatment	Yes
Secondary	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)		Twenty four weeks of treatment	Yes
Secondary	Superiority of renal function, defined as the proportion of patients experiencing a confirmed greater than or equal to 30% rise in serum creatinine		Twenty four weeks of treatment	Yes
Secondary	Superiority in proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI-75)		Twelve weeks of treatment	No