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

Dr.Reddy's Laboratories

Status and phase: Completed; Phase 2

Conditions: Psoriasis

Treatments: Drug: Placebo; Drug: XP 23829 800 mg QD; Drug: XP23829 400 mg QD; Drug: XP23829 400 mg BID

Study type: Interventional

Funder types: Industry

Identifiers

NCT02173301

XP-H-093

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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200 participants in 4 patient groups, including a placebo group

XP23829 400 mg QD (once daily)

Experimental group

Description:

After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg QD for 12 weeks including titration period

Treatment:

Drug: XP23829 400 mg QD

XP23829 800 mg QD

Experimental group

Description:

After 4-week screening period, eligible subjects will be randomized to XP23829 800 mg QD for 12 weeks including titration period

Treatment:

Drug: XP 23829 800 mg QD

XP23829 400 mg BID (twice daily)

Experimental group

Description:

After 4-week screening period, eligible subjects will be randomized to XP23829 400 mg BID for 12 weeks including titration period

Treatment:

Drug: XP23829 400 mg BID

Placebo

Placebo Comparator group

Description:

After 4-week screening period, eligible subjects will be randomized to Placebo for 12 weeks

Treatment:

Drug: Placebo