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

Phase 2

Completed

• Conditions: Psoriasis
• Interventions: Drug: XP23829 400 mg QD; Drug: XP 23829 800 mg QD; Drug: XP23829 400 mg BID; Drug: Placebo

• Registration Number: NCT02173301
• Lead Sponsor: Dr. Reddy's Laboratories Limited

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.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-23
• Study First Submitted QC: 2014-06-23
• Study First Posted: 2014-06-24
• Primary Completion: 2015-05
• Study Completion: 2015-08
• Status Verified: 2017-11
• Disposition First Submitted: 2017-11-03
• Disposition First Submitted QC: 2019-02-27
• Disposition First Posted: 2019-03-05
• Results First Submitted: 2022-03-17
• Results First Submitted QC: 2022-03-17
• Last Update Submitted: 2022-03-17
• Results First Posted: 2022-04-12
• Last Update Posted: 2022-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
XP23829 400 mg QD (once daily)	XP23829 400 mg QD	After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg QD for 12 weeks including titration period
XP23829 800 mg QD	XP 23829 800 mg QD	After 4-week screening period, eligible subjects will be randomized to XP23829 800 mg QD for 12 weeks including titration period
XP23829 400 mg BID (twice daily)	XP23829 400 mg BID	After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg BID for 12 weeks including titration period
Placebo	Placebo	After 4-week screening period, eligible subjects will be randomized to Placebo for 12 weeks

Primary Outcome Measures

Name	Time	Method
• The Percent Change in PASI (Psoriasis Area and Severity Index) Score From Baseline	12 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
• Proportion of Subjects Who Achieve a Reduction of 75% or Greater From Baseline in PASI (PASI-75)	Weeks 2, 4, 8, 12, 14 and 16	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.
• Proportion of Subjects Who Achieve a sPGA (Static Physician's Global Assessment) Score of Clear or Almost Clear	Weeks 2, 4, 8, 12, 14 and 16	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; 1. Almost clear: No thickening to minimal plaque elevation; Normal to slight pink coloration/faint erythema; Focal to minimal scaling; 2. Mild: Slight elevation/thickening; Pink to light red coloration; Predominantly fine scaling partially or mostly covering lesions; 3. Moderate: Clearly distinguishable/distinct thickening; Definite red coloration; Coarse scaling covering most plaques; 4. 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.

Trial Locations

Locations (1)

XenoPort Investigational Site; 🇺🇸 West Jordan, Utah, United States