Study to Evaluate Apo805K1 in Subjects With Moderate to Severe Chronic Plaque Psoriasis

A 12-week Randomized, Double-blind, Placebo-controlled, Multicenter, Multiple Sequential Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Apo805K1 in Subjects With Moderate to Severe Chronic Plaque Psoriasis

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of 12 weeks of treatment with Apo805K1 in subjects with moderate to severe chronic plaque psoriasis.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Apo805K1

Detailed Description

A) To evaluate the safety and tolerability of 12 weeks of treatment with Apo805K1

B) To evaluate the pharmacokinetics of Apo805K1 following daily administration for 14 days

C) To evaluate the efficacy and pharmacodynamics of Apo805K1

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2K4L5
      • Innovaderm Research Inc.
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
    • Los Angeles, California, United States, 90017
      • Axis Clinical Trials
  • Texas
    • Dallas, Texas, United States, 75246
      • Menter Dermatology Research Institute
    • Houston, Texas, United States, 77030
      • Center for Clinical Studies
    • Houston, Texas, United States, 77598
      • Center for Clinical Studies
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • The University of Utah

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

Main Inclusion Criteria:

• A clinical diagnosis of moderate to severe chronic plaque psoriasis for at least 6 months (before Baseline assessment) with current body surface area (BSA) involvement ≥10% and Psoriasis Area Severity Index (PASI) ≥10.
• Male and female subjects 18 to 65 years of age, inclusive.
• At least one psoriatic plaque ≥6 mm in diameter (in a location suitable for biopsy).
• Signed and witnessed written informed consent form obtained prior to the first study intervention, as well as the ability to adhere to study restrictions, appointments and evaluation schedule.

Main Exclusion Criteria:

• Treatment of psoriasis with biologic agents within 90 days prior to Baseline assessment and during the study.
• Treatment with methotrexate, cyclosporine, retinoids, hydroxyurea or other systemic agents within 30 days prior to Baseline assessment and during the study.
• Phototherapy within 30 days prior to Baseline assessment and during the study.
• Psoriasis topical therapy within 14 days prior to Baseline assessment and during the study (exception: non-medicated emollients and tar shampoo will be allowed).
• History of liver disease or abnormal liver enzymes
• Serum creatinine ≥1.5 times the upper limit of normal for age and sex-matched controls.
• Previous treatment with Apo805K1or Thymodepressin or other immunosuppressant drugs.
• Evidence of skin conditions other than psoriasis (e.g., eczema) that could interfere with psoriasis assessments.
• History of chronic infection or malignancy

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
Experimental: 10 mg Apo805K1, or placebo	Drug: Apo805K1; Sequential parallel dose escalation.
Experimental: 30 mg Apo805K1, or placebo	Drug: Apo805K1; Sequential parallel dose escalation.
Experimental: 60 mg Apo805K1, or placebo	Drug: Apo805K1; Sequential parallel dose escalation.
Experimental: 100 mg Apo805K1, or placebo	Drug: Apo805K1; Sequential parallel dose escalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events	The number of patients in each treatment group who reported at least 1 adverse event, including clinically significant changes from baseline in vital signs, 12-lead ECG, physical examinations and laboratory tests, from the time of the first dose until the last study visit.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Apo805K1 Following Multiple Doses, Assessed at Day 14	Cmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose. .	12 hours
Tmax of Apo805K1 Following Multiple Doses, Assessed at Day 14	Tmax for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose.	12 hours
AUC 0-infinity of Apo805K1 Following Multiple Doses, Assessed at Day 14	AUC 0-infinity for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose.	12 hours
T 1/2 of Apo805K1 Following Multiple Doses, Assessed at Day 14	T 1/2 for dosages of 10 mg, 30 mg, 60 mg, or 100 mg Apo805K1, determined on Day 14. Serial blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-dose.	12 hours
Efficacy of Apo805K1 as Assessed by Change From Baseline in Psoriasis Area Severity Index (PASI) Scores	PASI is a quantitative measure of psoriasis that combines an assessment of the severity of lesions and a measurement of how much of the body surface area is affected into a single score ranging from 0 (no disease) to 72 (maximal disease). Thus, a decrease in PASI score indicates improvement. This outcome measure compared the difference in change in PASI score from baseline to Week 12 between the active treatment groups and the placebo group.	Baseline to 12 Weeks
Efficacy of APO805K1 as Assessed by Achievement of PASI-75	The proportion of patients in each treatment group who achieved at least a 75% improvement in PASI score from baseline at Week 12	12 weeks
Efficacy of Apo805K1 as Assessed by Change From Baseline at Week 12 in Lattice System-Physician Global Assessment (LS-PGA) Scores	The LS-PGA is a standardized method for determining categories of psoriasis severity. The percentage of body surface area involved is assessed on a scale ranging from 1 (0%) to 7 (51-100%); measures of plaque severity (thickness, erythema, and scaling) are assessed using a 4-point scale ranging from "none" to "marked"; and an algorithm is used to combine the above scores to determine a final score on a scale ranging from 0 (clear) to 7 (very severe). Thus, a decrease in LS-PGA score indicates improvement. This outcome measure compared the difference in change in LS-PGA score from baseline to Week 12 between the active treatment groups and the placebo group.	Baseline to 12 weeks
Efficacy of Apo805K1 as Assessed by Change From Baseline to Week 12 in Physician Global Assessment (PGA) Score	In the PGA, the physician assigns a single estimate of a patient's overall severity of the disease using a scale ranging from 0 (Clear) to 7 (Severe). (Unlike the LS-PGA, the individual elements of psoriasis plaque morphology or degree of body surface area involvement are not quantified.) Thus, a decrease in PGA score indicates improvement. This outcome measure compared the difference in change in PGA score from baseline to Week 12 between the active treatment groups and the placebo group.	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: ApoPharma

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: November 30, 2011
• First Submitted That Met QC Criteria: November 30, 2011
• First Posted (Estimate): December 2, 2011

Study Record Updates

• Last Update Posted (Estimate): February 20, 2015
• Last Update Submitted That Met QC Criteria: February 9, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Mild to Moderate Chronic Plaque Psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: AP03-0210