Randomized Placebo-controlled Study of ISA247 in Plaque Psoriasis (SPIRIT)

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

The purpose of this study is to determine which dose of voclosporin is effective in the treatment of plaque psoriasis compared to placebo.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: voclosporin

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.

• Study Type: Interventional
• Enrollment (Actual): 451
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2S 3B3
      • Isotechnika Investigational Site
    • Edmonton, Alberta, Canada, T5J 3S9
      • Isotechnika Investigational Site'
    • Edmonton, Alberta, Canada, T5J 3S9
      • Isotechnika Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E8
      • Isotechnika Investigational Site
    • Vancouver, British Columbia, Canada, V5Z 3Y1
      • Isotechnika Investigational Site
    • Victoria, British Columbia, Canada, V8R 6V4
      • Isotechnika Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • Isotechnika Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Isotechnika Investigational Site
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3E1
      • Isotechnika Investigational Site
    • St. John's, Newfoundland and Labrador, Canada, A1B 4F8
      • Isotechnika Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1Z4
      • Isotechnika Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1V6
      • Isotechnika Investigational Site
    • London, Ontario, Canada, N5X 2P1
      • Isotechnika Investigational Site
    • London, Ontario, Canada, N6A 3H7
      • Isotechnika Investigational Site
    • Maple, Ontario, Canada, L4K 5V2
      • Isotechnika Investigational Site
    • Markham, Ontario, Canada, L3P 1A8
      • Isotechnika Investigational Site
    • Newmarket, Ontario, Canada, L3Y 6P5
      • Isotechnika Investigational Site
    • North Bay, Ontario, Canada, P1B 3Z7
      • Isotechnika Investigational Site
    • North Bay, Ontario, Canada, L4M 6L2
      • Isotechnika Investigational Site
    • Oakville, Ontario, Canada, L6K 1E1
      • Isotechnika Investigational Site
    • Oshawa, Ontario, Canada, L1H 1B9
      • Isotechnika Investigational Site
    • Toronto, Ontario, Canada, M5V 2T3
      • Isotechnika Investigational Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Isotechnika Investigational Site
    • Windsor, Ontario, Canada, N8W 1E6
      • Isotechnika Investigational Site
    • Windsor, Ontario, Canada, N8W 5L7
      • Isotechnika Investigational Site
  • Quebec
    • Laval, Quebec, Canada, H7G 2C0
      • Isotechnika Investigational Site
    • Montreal, Quebec, Canada, H2K 4L5
      • Isotechnika Investigational Site
    • Montreal, Quebec, Canada, H3G 1C6
      • Isotechnika Investigational Site
    • Pointe Claire, Quebec, Canada, H9R 4S3
      • Isotechnika Investigational Site
    • Sherbrooke, Quebec, Canada, J1J 2B8
      • Isotechnika Investigational Site
    • Ste. Foy, Quebec, Canada, G1V 4X7
      • Isotechnika Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator: 1; Placebo	Drug: Placebo; Placebo
Active Comparator: Voclosporin 0.2 mg/kg po BID	Drug: voclosporin; voclosporin 0.2, 0.3, or 0.4 mg/kg po BID
Active Comparator: Voclosporin 0.3 mg/kg po BID	Drug: voclosporin; voclosporin 0.2, 0.3, or 0.4 mg/kg po BID
Active Comparator: Voclosporin 0.4 mg/kg po BID	Drug: voclosporin; voclosporin 0.2, 0.3, or 0.4 mg/kg po BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Achieving a PASI-75 at 12 Weeks at Each of the 3 Dose Levels of Voclosporin.	Proportion of subjects achieving a PASI-75 at 12 weeks at each of the 3 dose levels of voclosporin.	Twelve Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To Investigate the Safety and Tolerability of Voclosporin.	Twelve and twenty four weeks
To Investigate the Pharmacokinetics and Pharmacodynamics of Voclosporin After Chronic Dosing in a Subset of Subjects.	Twelve and twenty four weeks
To Evaluate the Effect of Voclosporin on Subject Quality of Life	Twelve and twenty four weeks

Collaborators and Investigators

• Sponsor: Aurinia Pharmaceuticals Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): October 1, 2005
• Study Completion (Actual): October 1, 2005

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimate): October 27, 2005

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Humans; Immunosuppression; Quality of Life; Randomized Controlled Trials; Adult; Female; Male; Treatment Outcome; Chronic Disease; Middle Aged; Double-Blind Method; Severity of Illness Index; Dermatologic Agents
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: ISA04-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO