Moderate to severe chronic plaque psoriasis MedDRA version: 9.1 Level: LLT Classification code 10037153 Term: Psoriasis
Conditions
Sponsors
Actelion Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 18 to 60 years (inclusive). 2. For female subjects, a woman of childbearing potential must: • have a negative serum pregnancy test at screening and a negative urine pregnancy test at randomization (before the first study drug intake). • agree to use two methods of contraception from the screening visit until 2 months after study drug discontinuation. Of the two contraceptive methods, one must be from Group 1, and one must be from Group 2, defined as follows: Group 1: Oral, implantable, transdermal or injectable hormonal contraceptives, intrauterine devices, female sterilization (tubal ligation), or partner’s sterilization (vasectomy). If a hormonal contraceptive will be chosen from this group, it must have been taken for at least 1 month prior to randomization (i.e., Visit 2). Group 2: Condoms, diaphragm or cervical cap, all in combination with spermicide. Abstention and rhythm are not acceptable methods of contraception. A woman is considered to be of childbearing potential unless she meets at least one of the following criteria: • Previous bilateral salpingo-oophorectomy, or hysterectomy. • Premature ovarian failure confirmed by a specialist gynecologist. • Age >= 50 years and not treated with any kind of hormone replacement therapy (HRT) for at least 2 years prior to screening, with amenorrhea for at least 24 consecutive months prior to screening, and a serum follicle-stimulating hormone (FSH) level of > 40 IU/L at screening. • Age >= 55 years and treated with HRT prior to screening with appropriate medical documentation of spontaneous amenorrhea for at least 24 consecutive months. 3. Moderate to severe plaque psoriasis with body surface area (BSA) involvement > 10% and PASI score > 10, which is stable for at least 3 months, requires systemic treatment, and for which treatment in a placebo-controlled study of an investigational drug can be justified. 4. Signed informed consent form prior to initiation of any study-mandated procedure. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Breast-feeding women. 2. Generalized erythrodermic, generalized pustular psoriasis (von Zumbusch), guttate, and palmo-plantar psoriasis. 3. Treatment with: • Ultraviolet B (UVB) therapy, psoralen-ultraviolet-light (PUVA) therapy and topical treatments for psoriasis other than emollients within 1 month prior to start of study drug. • Oral retinoids, methotrexate, cyclosporine and systemic corticosteroids within 1 month prior to start of study drug. • Approved immunosuppressive or immunomodulatory biologic agents (e.g., infliximab, etanercept, alefacept, efalizumab, adalimumab) within 3 months prior to start of study drug. • Investigational non lymphocyte-depleting biologic agents (recombinant proteins or monoclonal antibodies) within 6 months prior to start of study drug or lymphocyte-depleting biologic agents at any point in time. • Other systemic immunosuppressive drugs (e.g., mycophenolic acid, sirolimus) within 3 months prior to start of study drug. • Treatment with another investigational drug within 3 months prior to start of study drug. • Vaccination with live vaccines within 3 months prior to start of study drug. • Treatment with ß-blockers, diltiazem, verapamil, digoxin, amiodarone, and lithium (for any indication) within 1 month prior to start of study drug. 4. Subjects currently treated for autoimmune disorders other than psoriasis. 5. Ongoing bacterial, viral or fungal infection (with the exception of onychomycosis and dermatomycosis), positive hepatitis B surface antigen or hepatitis C antibody tests. 6. Congenital or acquired severe immunodeficiency or known human immunodeficiency virus (HIV) infection. 7. History or presence of malignancy (except for basal or squamous cell skin lesions which have been surgically excised), lymphoproliferative disease and subjects who received total lymphoid irradiation or bone marrow transplantation. 8. Poorly controlled type I or II diabetes. 9. History or presence of macular edema or diabetic retinopathy (as confirmed by fundoscopy within 28 days prior to randomization). 10. Any of the following cardiovascular conditions: • Resting heart rate (HR) 180 ms. • Symptomatic ischemic heart disease. • History of valvular heart disease. • History of heart failure. • History or presence of rhythm disorders (e.g., sino atrial heart block, second degree atrioventricular [AV] block, third degree AV-block, sick sinus syndrome, symptomatic bradycardia, atrial flutter or atrial fibrillation) or subjects who receive anti-arrhythmic therapy. • History of syncope. • Arterial hypertension uncontrolled by medications. 11. Any of the following pulmonary conditions: • Moderate and severe bronchial asthma or chronic obstructive pulmonary disease (COPD) stage II–IV (i.e., forced expiratory volume in 1 second [FEV1] 2-fold the upper limit of the normal range (ULN). 13. Any of the following abnormal laboratory values: • Hemoglobin (Hb) < 10g/dL. • White blood cells (WBC) count < 3,500/µL. • Lymphoc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate the efficacy of ACT-128800 20 mg once daily on Psoriasis Area and Severity Index (PASI) at Week 6 in subjects with moderate to severe chronic plaque psoriasis.;Secondary Objective: • To evaluate the safety and tolerability of ACT-128800 20 mg once daily for 6 weeks in subjects with moderate to severe chronic plaque psoriasis. • To investigate the pharmacokinetics and pharmacodynamics of ACT-128800 in subjects with moderate to severe chronic plaque psoriasis.;Primary end point(s): • PASI percent change relative to baseline (BL) at Week 6 visit. The difference to be detected is a placebo-corrected mean decrease of 30 units. Percentage change of PASI is expected to be normally distributed with a standard deviation (SD) of 29%. For each of the following criteria, within the cohort of active-treated subjects, the primary endpoint will be further explored in the two subsets of subjects who fulfill (Group A) or do not fulfill (Group B): – Peripheral total lymphocyte count = 0.8 10^9/L at Week 6 visit, 6 hours post-dose. – Reduction of peripheral total lymphocyte count by = 80% compared to baseline at Week 6 visit, 6 hours post-dose. – Peripheral total lymphocyte count = 0.5 10^9/L at Week 6 visit, 6 hours post-dose | — |
Countries
Austria, France, Germany, Hungary
Outcome results
None listed