A Study to Assess the Efficacy and Safety of XP23829 in Subjects With Moderate-to-Severe Chronic Plaque-Type Psoriasis

A Phase 2, Randomized, Double-Blind, Multicenter, Parallel-Group, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Dose Levels of XP23829 in Subjects With Moderate-to-Severe Chronic Plaque-Type Psoriasis

The study objectives are the following:

1. To evaluate the efficacy of 3 doses of XP23829 compared to placebo for the treatment of moderate-to-severe chronic plaque-type psoriasis.
2. To evaluate the safety and tolerability of XP23829 in subjects with psoriasis.
3. To evaluate the pharmacodynamics (PD) of XP23829 through immunological analysis of peripheral blood samples.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: XP23829 400 mg QD; Drug: XP 23829 800 mg QD; Drug: XP23829 400 mg BID

Detailed Description

Study Design : This is a , multi-center, double blind, placebo-controlled, phase 2 (dose-finding) efficacy and safety study in which subjects with moderate-to- severe chronic plaque-type psoriasis will be randomized in a 1:1:1:1 allocation ratio to 1 of 3 active doses of XP23829 or placebo. Approximately 50 subjects will be enrolled into each treatment group.

Study Periods: The study includes a 4-week screening phase, a 12-week treatment phase (with 9 weeks of XP23829 or placebo at the maintenance dose), and a 4-week observational post-treatment follow-up phase. A treatment-free follow-up period is designed to evaluate safety and disease relapse and rebound.

Specifically, the study periods are as follows:

1. Screening Phase: Weeks -4 through 0

2. Treatment phase included:

   1. Titration Phase: Weeks 1 through 3
   2. Double-Blind Maintenance Phase: Weeks 4 through 12
3. Post-treatment follow-up: Weeks 13 through 16

Efficacy assessments will be performed in the clinic at Baseline (Visit 2) and at the end of Weeks 2, 4, 8, 12, 14, and 16.

Patient-reported outcome measures will be assessed in the clinic at Baseline and at Week 12.

Blood samples for pharmacodynamic (PD) assessments will be collected at Baseline and at Weeks 4, 8, 12 and 16. PD assessments will be conducted in all subjects, with the intent of evaluating psoriasis-associated inflammatory markers.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • XenoPort Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • XenoPort Investigational Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • XenoPort Investigational Site
  • California
    • Encinitas, California, United States, 92024
      • XenoPort Investigational Site
    • Fremont, California, United States, 94538
      • XenoPort Investigational Site
    • Fullerton, California, United States, 92663
      • XenoPort Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80210
      • XenoPort Investigational Site
  • Georgia
    • Snellville, Georgia, United States, 30078
      • XenoPort Investigational Site
  • Illinois
    • Buffalo Grove, Illinois, United States, 60089
      • XenoPort Investigational Site
  • Indiana
    • Carmel, Indiana, United States, 46032
      • XenoPort Investigational Site
    • South Bend, Indiana, United States, 46617
      • XenoPort Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • XenoPort Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • XenoPort Investigational Site
    • Owensboro, Kentucky, United States, 42303
      • XenoPort Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • XenoPort Investigational Site
    • Watertown, Massachusetts, United States, 02472
      • XenoPort Investigational Site
  • Michigan
    • Troy, Michigan, United States, 48084
      • XenoPort Investigational Site
    • Warren, Michigan, United States, 48088
      • XenoPort Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • XenoPort Investigational Site
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • XenoPort Investigational Site
    • Verona, New Jersey, United States, 07044
      • XenoPort Investigational Site
  • New York
    • Rochester, New York, United States, 14623
      • XenoPort Investigational Site
    • Stony Brook, New York, United States, 11790
      • XenoPort Investigational Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • XenoPort Investigational Site
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • XenoPort Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • XenoPort Investigational Site
    • Dallas, Texas, United States, 75231
      • XenoPort Investigational Site
    • Dallas, Texas, United States, 75246
      • XenoPort Investigational Site
    • San Antonio, Texas, United States, 78218
      • XenoPort Investigational Site
    • San Antonio, Texas, United States, 78229
      • XenoPort Investigational Site
  • Utah
    • West Jordan, Utah, United States, 84088
      • XenoPort Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male and female subjects, age ≥ 18.
2. Stable, moderate-to-severe plaque-type psoriasis diagnosed for at least 6 months prior to randomization (no morphology changes or significant flares of disease activity in the last 6 months in the opinion of the investigator).

3. Severity of disease meeting all of the following three criteria prior to randomization:

   1. Psoriasis Area and Severity Index (PASI) score of 12 or greater
   2. Total Body Surface Area (BSA) affected by plaque psoriasis of 10% or greater
   3. Static Physician's Global Assessment (sPGA) score of 3 or greater
4. Must be a candidate for phototherapy and/or systemic therapy for psoriasis.

Exclusion Criteria:

1. Subjects with current inverse, erythrodermic, predominantly guttate, or pustular psoriasis.
2. Subjects with current drug-induced or drug-exacerbated psoriasis.
3. Subjects with moderate-to-severe psoriatic arthritis of any type; and subjects with mild psoriatic arthritis, who require systemic disease-modifying therapy.
4. Subjects with unstable or significant illness, including the presence of laboratory abnormalities at screening that in the opinion of the investigator would place the subject at unacceptable risk if he/she were to participate in the study.
5. Any skin condition (e.g. eczema) which confounds the ability to interpret data from the study.
6. Treatment with a topical anti-psoriatic therapy within 14 days prior to randomization (including topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin).
7. Phototherapy or prolonged sun exposure or use of ultraviolet (UV) light sources within 28 days of randomization.
8. Use of investigational or approved biologic treatments that are known to affect psoriasis, such as adalimumab, etanercept, golimumab or infliximab within 12 weeks of randomization and ustekinumab within 24 weeks of randomization.
9. Use of systemic medications (non-biologics) that are known to affect psoriasis (including but not limited to oral corticosteroids, cyclosporine, methotrexate, lithium, and beta-adrenergic blockers) within 4 weeks of randomization, or 5 half-lives, whichever is longer.
10. Prior treatment with Dimethyl Fumarate (Fumaderm® or Tecfidera®) or any other Fumaric Acid Ester (FAE) containing products.
11. Have failed (due to inadequate response) more than 3 approved systemic agents for the treatment of psoriasis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XP23829 400 mg QD (once daily); After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg QD for 12 weeks including titration period	Drug: XP23829 400 mg QD; active dose 1; Other Names: Tepilamide fumarate 400 mg QD; PPC-06 400 mg QD
Experimental: XP23829 800 mg QD; After 4-week screening period, eligible subjects will be randomized to XP23829 800 mg QD for 12 weeks including titration period	Drug: XP 23829 800 mg QD; active dose 2; Other Names: Tepilamide fumarate 800 mg QD; PPC-06 800 mg QD
Experimental: XP23829 400 mg BID (twice daily); After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg BID for 12 weeks including titration period	Drug: XP23829 400 mg BID; active dose 3; Other Names: Tepilamide fumarate 400 mg BID; PPC-06 400 mg BID
Placebo Comparator: Placebo; After 4-week screening period, eligible subjects will be randomized to Placebo for 12 weeks	Drug: Placebo; control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• The Percent Change in PASI (Psoriasis Area and Severity Index) Score From Baseline	The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Proportion of Subjects Who Achieve a Reduction of 75% or Greater From Baseline in PASI (PASI-75)	The percentage of subjects who achieve a reduction of 75% or greater from Baseline in the Psoriasis Area and Severity Index score (PASI-75) at efficacy assessments conducted at Weeks 2, 4, 8, 12, 14 and 16. The PASI is a measure of the average redness, thickness, and scaliness of the lesions (each graded on a 0-4 scale) and is weighted by the area of involvement. The minimum possible score on this scale is '0', while the maximum score on this scale is 72. A lower score on this scale at the end of the study indicates an improvement in the condition of subject.	Weeks 2, 4, 8, 12, 14 and 16
• Proportion of Subjects Who Achieve a sPGA (Static Physician's Global Assessment) Score of Clear or Almost Clear	The Percentage of subjects who achieve the static Physician's Global Assessment (sPGA) score of 'clear' or 'almost clear' (sPGA score 0 or 1) at efficacy assessments conducted at Weeks 2, 4, 8, 12, 14 and 16. Score Grade : Definition - 0 Clear: No signs of psoriasis; Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling; Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions; Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques; Severe: Marked thickening with hard/sharp edges; Bright to deep dark red coloration; Thick/coarse scaling covering almost all or all lesions A lower score on this scale at the end of the study indicates an improvement in the disease condition.	Weeks 2, 4, 8, 12, 14 and 16

Collaborators and Investigators

• Sponsor: Dr. Reddy's Laboratories Limited
• Collaborators: XenoPort, Inc.
• Investigators: Study Director: Dmitri Lissin, M.D., XenoPort, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 23, 2014
• First Submitted That Met QC Criteria: June 23, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: XP-H-093