Evaluation of safety, pharmacokinetics, and anti-psoriatic efficacy to assess SOR007 Ointment in topical formulations

This is a two-center, randomized, placebo- and active comparator-controlled trial that will be double-blind for the investigational products (IPs) and observer-blind for the active comparator with intra-individual comparison of treatments. Twelve male and post-menopausal female volunteer subjects, aged 18 years or older, with psoriasis vulgaris and mild or moderate chronic plaque(s) in a stable phase and an area sufficient for six treatment fields, will be enrolled. SOR007 Ointment will be administered topically at four concentrations (0.15%, 0.3%, 1%, and 2%), in addition to a placebo ointment (SOR007 without the active pharmaceutical ingredient) and an active comparator, Taclonex® Ointment (calcipotriene 0.005 % and betamethasone dipropionate 0.064 %). Treatments will be administered once daily, 10 times over a 12-day trial period. Assessments will include safety, pharmacokinetics (PK), and preliminary efficacy as determined by measurement of psoriatic infiltrate using 22-megahertz (MHz) sonography as well as clinical scoring on a 5-point scale. Subjects who withdraw early for reasons unrelated to investigational product adverse events (AEs) will be replaced.

Inclusion Criteria:

• men and surgically sterile or post-menopausal (at least since 12 months amenorrhoea) women aged 18 years or older. The non-childbearing potential of women needs to be confirmed by medical record or in writing by a gynecologist, if that is not possible a follicle stimulating hormone (FSH) test will be performed on female subjects to confirm menopause, unless they are receiving hormonal replacement therapy for treatment of menopause symptoms;
• subjects with psoriasis vulgaris in a chronic stable phase and mild to moderate plaque(s) with up to three plaque areas sufficient for six treatment fields;
• the target lesion(s) should be on the trunk or extremities (excluding palms/soles); psoriatic lesion on the knees or elbows are not to be used as a target lesion;
• plaques to be treated should have a comparable psoriatic infiltrate thickness of at least 200 μm;
• the physical examination of the skin must be without disease findings other than psoriasis vulgaris unless the investigator considers an abnormality to be irrelevant to the outcome of the clinical trial;
• male volunteers must agree to sexual abstinence or use adequate contraception when sexually active in combination with their female partners, if they are of childbearing potential. That means the volunteer must be vasectomized or use a condom and his female partner must either be surgically sterile (hysterectomy or tubal ligation) or agree to use a reliable method of contraception with a failure rate of less than 1 % per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, or non-DalKon Shield intra-uterine devices [IUDs]. This applies from signing of the informed consent form until 90 days after the last study drug administration. Methods of contraception must have been effective for at least 30 days on the day of signing the informed consent form. Male volunteers must also refrain from sperm donation from signing of the informed consent form until 90 days after the last study drug administration;
• written informed consent obtained.

Exclusion Criteria:

• pregnancy and nursing;
• other skin disease or condition noted on physical examination that is considered by the investigator to be relevant to the outcome of the trial;
• subjects with acute psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica and pustular psoriasis;
• any topical antipsoriatics on plaques potentially to be treated in this trial (including corticosteroids, vitamin D analogues, immunomodulators, retinoids, dithranol and tar, except for salicylic acid and except for treatment on the face, ears and scalp) in the 4 weeks before first treatment and/or during the trial;
• systemic treatment with antipsoriatics e.g. corticosteroids, cytostatics, retinoids, dimethylfumarate in the three months before first treatment and during the trial;
• systemic treatment with biological treatments: ustekinumab or secukinumab within six months or adalimumab, infliximab and etanercept within three months before first treatment and during the trial;
• UV-therapy within four weeks before first treatment and during the trial;
• treatment with systemic or locally acting medications which might have countered or influenced the trial aim (medications which are known to provoke or aggravate psoriasis, e.g. antimalarial drugs, lithium) within eight weeks before first treatment and/or during the trial. Beta-blockers or angiotensin-converting enzyme (ACE) inhibitors are allowed if on a stable dose for 3 months before study medication initiation;
• intake of Anticoagulant Drugs, e.g. Warfarin, Coumadin. Antiplatelet Drugs e.g. Acetyl salicylic acid are permitted unless considered contraindicated by the investigator for blood withdrawal for PK analyses;
• known allergic reactions, irritations or sensitivity to the active ingredients or other components of the IPs;
• known allergic reactions, irritations or sensitivity to the comparator's active ingredient and/or components;
• contraindications according to summary of product characteristics of the active comparator;
• evidence of drug or alcohol abuse;
• symptoms of a clinically significant illness that may place the subject at risk by trial participation or influence the outcome of the trial in the four weeks before first treatment and during the trial;
• participation in the treatment phase of another clinical trial within the last four weeks prior to first treatment in this clinical trial;
• in the opinion of the investigator or physician performing the initial examination the subject should not participate in the trial, e.g. due to probable noncompliance or inability to understand the trial and give adequately informed consent;
• close affiliation with the investigator (e.g. a close relative) or persons working at bioskin GmbH or Modoc or subject is an employee of sponsor;
• subject is institutionalized because of legal or regulatory order.