Clinical trial NCT02173301: A Study to Assess the Efficacy and Safety of XP23829 in Subjects With Moderate-to-Severe Chronic Plaque-Type Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Lead sponsor: Dr. Reddy's Laboratories Limited
Sponsor class: INDUSTRY
Collaborators: name: XenoPort, Inc.
First posted: 2014-06-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: • The Percent Change in PASI (Psoriasis Area and Severity Index) Score From Baseline
timeFrame: 12 Weeks
Secondary outcomes:
measure: • Proportion of Subjects Who Achieve a Reduction of 75% or Greater From Baseline in PASI (PASI-75)
timeFrame: Weeks 2, 4, 8, 12, 14 and 16
measure: • Proportion of Subjects Who Achieve a sPGA (Static Physician's Global Assessment) Score of Clear or Almost Clear
timeFrame: Weeks 2, 4, 8, 12, 14 and 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: XenoPort Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: XenoPort Investigational Site
state: Arizona
city: Hot Springs
country: United States
facility: XenoPort Investigational Site
state: Arkansas
city: Encinitas
country: United States
facility: XenoPort Investigational Site
state: California
city: Fremont
country: United States
facility: XenoPort Investigational Site
state: California
city: Fullerton
country: United States
facility: XenoPort Investigational Site
state: California
city: Denver
country: United States
facility: XenoPort Investigational Site
state: Colorado
city: Snellville
country: United States
facility: XenoPort Investigational Site
state: Georgia
city: Buffalo Grove
country: United States
facility: XenoPort Investigational Site
state: Illinois
city: Carmel
country: United States
facility: XenoPort Investigational Site
state: Indiana
city: South Bend
country: United States
facility: XenoPort Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: XenoPort Investigational Site
state: Kansas
city: Louisville
country: United States
facility: XenoPort Investigational Site
state: Kentucky
city: Owensboro
country: United States
facility: XenoPort Investigational Site
state: Kentucky
city: Boston
country: United States
facility: XenoPort Investigational Site
state: Massachusetts
city: Watertown
country: United States
facility: XenoPort Investigational Site
state: Massachusetts
city: Troy
country: United States
facility: XenoPort Investigational Site
state: Michigan
city: Warren
country: United States
facility: XenoPort Investigational Site
state: Michigan
city: Omaha
country: United States
facility: XenoPort Investigational Site
state: Nebraska
city: East Windsor
country: United States
facility: XenoPort Investigational Site
state: New Jersey
city: Verona
country: United States
facility: XenoPort Investigational Site
state: New Jersey
city: Rochester
country: United States
facility: XenoPort Investigational Site
state: New York
city: Stony Brook
country: United States
facility: XenoPort Investigational Site
state: New York
city: High Point
country: United States
facility: XenoPort Investigational Site
state: North Carolina
city: Goodlettsville
country: United States
facility: XenoPort Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: XenoPort Investigational Site
state: Texas
city: Dallas
country: United States
facility: XenoPort Investigational Site
state: Texas
city: Dallas
country: United States
facility: XenoPort Investigational Site
state: Texas
city: San Antonio
country: United States
facility: XenoPort Investigational Site
state: Texas
city: San Antonio
country: United States
facility: XenoPort Investigational Site
state: Texas
city: West Jordan
country: United States
facility: XenoPort Investigational Site
state: Utah
Study officials:
affiliation: XenoPort, Inc.
name: Dmitri Lissin, M.D.
role: STUDY_DIRECTOR
References: