SHP-141C in Plaque Type Psoriasis

A Double-Blind, Within-Subject Randomised, Placebo-Controlled, Proof of Concept, Comparison Study of SHP-141C Topical Cream in Psoriasis, Using the Microplaque Assay.

The purpose of this study is to assess the safety, tolerability and clinical activity of the SHP-141C topical cream formulations in patients with plaque type psoriasis.

Study Overview

• Status: Completed
• Conditions: Plaque Type Psoriasis
• Intervention / Treatment: Drug: SHP-141C; Drug: Placebo to SHP-141C; Drug: Betamethasone Valerate; Drug: Calcipotriol

Detailed Description

Psoriasis is a chronic, relapsing immunoinflammatory disorder. Chronic plaque psoriasis is the most common (85% - 90%) type. Cutaneous features of individual plaques include circular with centrifugal expansion, induration with sharp demarcation from surrounding skin, erythema and hyperkeratosis. Psoriasis has a negative impact on physical and mental aspects of life that is similar to other major chronic conditions. The modalities of psoriasis treatments can be divided into four main categories: topical, phototherapy, systemic drug therapies and systemic biological treatments. The currently available treatments for psoriasis result in either disease suppression or disease remission.There are many treatment options for the management of psoriasis using topical modalities; however all are lacking with respect to patient satisfaction and durability of treatment. Most current topical treatments, and many treatments in development, are based on modifications of a steroid structure or on Vitamin D. Recent research has identified a broad role for histone deacetylase (HDAC) proteins in numerous signaling pathways critical to cancer cell survival, such as epigenetic inheritance, gene regulation, mitosis,signal transduction and importantly, inflammation. Theoretically modulation of HDAC could lead to clinical benefit in inflammatory diseases.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Mild to moderate chronic plaque-type psoriasis.
2. psoriasis of at least one year.
3. Stable disease for at least two weeks prior to the commencement of study treatment.
4. One nominated target lesions must have areas of at least 86 x 57 mm2.
5. BMI of less than 35 kg/m2. -

Exclusion Criteria:

1. Dermatological Conditions

   • Subjects with erythrodermic, guttate, palmar, plantar or generalised pustular forms of psoriasis.
   • Subjects with scalp, palmar or plantar psoriasis only.
   • Subjects with any skin condition other than psoriasis, in particular eczema, cutaneous infections, significant sun damage or an inherited skin disorder (other than psoriasis).

2. Concurrent Medical Conditions

   • History of clinically significant intercurrent disease of any type (other than psoriasis).
   • A history of moderate or severe asthma during the last 10 years.
   • Major chronic inflammatory disease .
   • Congenital immunodeficiency or cancer prone syndrome.
   • History of abnormal bleeding tendencies or thrombophlebitis, or a history of Hepatitis B, Hepatitis C or HIV infection.
   • History of malignancy (other than adequately treated skin carcinoma or carcinoma-in-situ of the cervix).

3. Laboratory Status

   • Any evidence of organ dysfunction, which is confirmed on re-examination to be clinically significant (i.e. in the opinion of the Medical Officer would jeopardise the safety of the subject or impact on the validity of the study results),
   • A creatinine clearance of less than 75 mL/min.
   • Liver function test > 1.5 x upper limit of normal other than an isolated bilirubin.
   • Hepatitis B surface antigen, Hepatitis C antibody, HIV antibodies.

4. Treatment with any of the following within 4 weeks prior to the commencement of study treatment and for the duration of the study:

   • Systemic retinoids.
   • Immunosuppressant agents (e.g. methotrexate, cyclosporine, azathioprine, thioguanine prednisone, prednisolone, hydroxyurea or mycophenolate mofetil).
   • Phototherapy or photochemotherapy.
   • High potency topical corticosteroids.
   • "Alternative medicine" treatments for psoriasis.
   • Prolonged sun exposure or tanning bed use, which may in the opinion of the Investigator, modify disease activity.

5. Topical treatment of the 2 target lesions with any of the following within 2 weeks prior to commencement of study treatment and for the duration of the study

   • Moderate potency topical corticosteroids.
   • Vitamin D analogues and topical retinoids.
   • Keratolytics, coal tar and dithranol.
6. Concurrent Medications Subjects have received or anticipate receiving a new medicine (prescription, over-the-counter or herbal), given systemically or topically, within 14 days prior to the start of dosing. Subjects may be enrolled if stable on existing therapy (having been on it for at least 60 days) as determined by the Principal Investigator.
7. Hypersensitivity History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations or other topical agents. A known hypersensitivity to lignocaine, or all surgical dressings that may be used in the study procedures.
8. Females who are lactating, pregnant or planning to become pregnant.
9. Drug and Alcohol Abuse History of, or current evidence of, abuse of alcohol or any drug substance, licit or illicit, or positive urine drug and alcohol screen for drugs of abuse and alcohol.
10. Psychiatric Disorder History of any psychiatric illness which may impair the ability to provide written informed consent
11. Participation in a research study within 30 days of the start of dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHP-141C & Placebo & Calcipotriol & Betamethasone Valerate; A 100 mg dose of SHP-141C cream at three concentrations (0.5%, 1.0% and 2.0%), a matched placebo cream and two reference treatments: Calcipotriol 0.005% cream and Betamethasone Valerate 0.02% cream, applied topically to a selected plaque on each subject, six times per week over 28 days for a total of 24 doses.	Drug: SHP-141C; Topical Cream; Other Names: SHAPE; Drug: Placebo to SHP-141C; Placebo Topical Cream; Other Names: Placebo to SHAPE; Drug: Betamethasone Valerate; Topical cream, 0.02%; Other Names: Celestone-M; Drug: Calcipotriol; Topical cream, 0.005%; Other Names: Daivonex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Local Plaque Severity Index (LPSI)	Measurement of plaque severity including erythema, induration, and desquamation.	Baseline, day 15, day 33

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with adverse events	Adverse event data for each subject will be collected.	daily to and including Day33

Collaborators and Investigators

• Sponsor: TetraLogic Pharmaceuticals
• Investigators: Principal Investigator: Peter Foley, The Alfred

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: July 11, 2012
• First Submitted That Met QC Criteria: July 17, 2012
• First Posted (Estimate): July 20, 2012

Study Record Updates

• Last Update Posted (Estimate): July 11, 2014
• Last Update Submitted That Met QC Criteria: July 10, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Calcipotriene; Betamethasone sodium phosphate
• Other Study ID Numbers: SHP-141C-002