A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Plaque Psoriasis

A Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Determine the Efficacy, Safety and Tolerability of Once Daily Oral ZPL-3893787- 18 (30 mg) Administered for 12 Weeks in Adult Subjects With Moderate to Severe Plaque Psoriasis

This was a randomized, double blind, placebo controlled, parallel group study in 129 subjects with moderate to severe psoriasis with a PASI score of at least 10. Following run-in, subjects were randomized and received either oral 30 mg ZPL-3893787 once daily or placebo once daily for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Placebo; Drug: ZPL-3893787

Detailed Description

This was a randomized, double blind, placebo controlled, parallel group study in 129 subjects with moderate to severe psoriasis with a Psoriasis Area and Severity Index (PASI) score of at least 10 and an Investigator's Global Assessment (IGA) of 3 (0-4 scale). Following run-in subjects received either oral 30 mg ZPL-3893787 once daily or placebo once daily for 12 weeks. Subjects attended the clinic at Baseline (Day 0) when they were reviewed and confirmed they met inclusion/exclusion criteria. Subjects were then randomized and received either oral 30 mg ZPL-3893787 once daily or placebo once daily for 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Belgium Study Centre
  • Brussels, Belgium, 1090
    • Belgium Study Centre
  • Brussels, Belgium, 1200
    • Belgium Study Centre
  • Gent, Belgium, 9000
    • Belgium Study Centre
  • Leuven, Belgium, 3000
    • Belgium Study Centre
  • Liège, Belgium, 4000
    • Belgium Study Centre
• Germany
  • Berlin, Germany, 10117
    • German Study Centre
  • Goch, Germany, 47574
    • German Study Centre
  • Hamburg, Germany, 20354
    • German Study Centre
  • Hanover, Germany, 30625
    • German Study Centre
  • Mainz, Germany, 55131
    • German Study Centre
  • Münster, Germany, 48149
    • German Study Centre
• Poland
  • Bialystok, Poland, 15-430
    • Polish Study Centre
  • Gdańsk, Poland, 80-405
    • Polish Study Centre
  • Lodz, Poland, 90-153
    • Polish Study Centre
  • Lublin, Poland, 20-552
    • Polish Study Centre
  • Poznan, Poland, 60-214
    • Polish Study Centre
  • Tarnow, Poland, , 33-100
    • Polish Study Centre
  • Wrocław, Poland, 50-220
    • Polish Study Centre
  • Łódź, Poland, 90-553
    • Polish Study Centre
• United Kingdom
  • Blackpool, United Kingdom, FY2 0JH
    • UK Study Centre
  • Bridgetown, United Kingdom, WS110BN
    • UK Study Centre
  • Leeds, United Kingdom, WS110BN
    • UK Study Centre
  • Manchester, United Kingdom, M13 9NQ
    • UK Study Centre

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:

• A documented history of moderate to severe plaque psoriasis for at least 6 months prior to screening.
• Male or female, aged ≥18 years.
• Psoriasis Area and Severity Index (PASI) ≥10 at both Screening and Day 0.
• An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 0.
• Psoriasis affecting ≥10% body surface area (BSA) at Screening and Day 0.

Exclusion Criteria:

• Current diagnosis of Pustular, Guttate, Erythrodermic, exfoliative or only nail psoriasis or a diagnosis of inverse psoriasis without having plaque psoriasis.
• Concurrent skin disease (e.g. acne) of such severity in the study area that it could interfere with the study evaluation or presence of skin comorbidities that may interfere with study assessments.
• Active skin infections (e.g. impetigo, abscesses) or any other clinically apparent infections.
• Biologic treatments for psoriasis (e.g. Enbrel, Humira, Stelara, Cosentyx) within 3 months of the start of the Run-In.
• Phototherapy (e.g. UVA, UVB, PUVA) within 4 weeks of the start of the Run-In.
• Oral calcineurin inhibitors and immunosuppressants (e.g. cyclosporine, azathioprine, methotrexate) within 4 weeks of the start of the Run-In.
• Systemic corticosteroids within 4 weeks of the start of the Run-In.
• Oral antihistamines and leukotriene inhibitors and tricyclic antidepressants within 1 week of the start of the Run-In.
• Topical steroids (any potency), topical calcineurin inhibitors (tacrolimus, pimecrolimus), salicylic acid and urea containing treatments and coaltar preparations, topical and oral retinoids and vitamin D derivatives, within 1 week of the start of the Run-In.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZPL-389; Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally once daily (OD) for 12 weeks.	Drug: ZPL-3893787; Other Names: ZPL389
Placebo Comparator: Placebo; Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Psoriasis Assessment of Severity Index (PASI) at Week 12	The PASI is an assessment routinely used for evaluating and grading the severity of psoriatic lesions and their response to therapy. PASI divides the body into 4 regions: the head, trunk, upper extremities (arms) and lower extremities (legs). Each of these areas is assessed separately for erythema, in duration and scaling; these symptoms are scored on a 5-point scale from 0-4, where 0 = no symptoms and 4 =very marked. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents a reduction of at least 75% from baseline in the PASI score.	From baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PASI-50 and PASI-75 Responders at Week 12	PASI-75 and PASI-50 are defined as a 75% and 50% reduction, respectively, from baseline in PASI score at Week 12.	From baseline to week 12
Improvement in Investigator Global Assessment (IGA) at Week 12	An overall assessment of the severity of psoriasis was made, by the investigator, using the IGA at each visit. IGA scores take values on a 5-point scale from 0-4, where 0 = clear to 4 = severe disease. Responder is defined as a score of clear or almost clear, or a reduction of ≥2 levels. Success is defined as a score of clear or almost clear. Subjects with discontinued and missing data categories at Week 12 were considered non-responders.	From baseline to week 12
Change From Baseline in the Numerical Rating Scale (NRS) for Pruritus (Worst Itch) at Week 12	The pruritus NRS is an assessment tool used to assess the subject's worst itch as a result of psoriasis in the last 12 hours. The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. They were asked the following question: On a scale of 0 (no itching) to 10 (itching as bad as you can imagine), please rate the worst itching that you felt over the last 12 hours.	From baseline to week 12
Patient Global Impression of Change (PGIC) a Week 12	At the end of treatment (Week 12) or early termination visit, the subject was asked to rate their degree of improvement (or worsening) of their psoriasis compared to before the start of treatment with study drug, using a 7-point scale, standardized PGIC. Since the start of the study (dosing), my overall status is: Very much improved; Much improved; Minimally improved; No change; Minimally worse; Much worse; Very much worse	From baseline to week 12
Change From Baseline in Body Surface Area (BSA) and Percentage Change From Baseline at Week 12	Assessment of the percentage of a subject's BSA affected by psoriasis was made by best estimates of the investigator at each visit. Hand-size measurement was considered to be the "best estimate" to measure the BSA by the investigators.	From baseline to week 12
Change From Baseline in the Daytime and Night Time NRS for Pruritus (Worst Itch) at Week 12	The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. They were asked the following question: On a scale of 0 (no itching) to 10 (itching as bad as you can imagine), please rate the worst itching that you felt over the last 12 hours.	From baseline to week 12
Change From Baseline in the NRS for Sleep Disturbance at Week 12	In the morning subjects were asked the following question to determine the level of sleep disturbance due to itching: On a scale of 0 (no sleep disturbance) to 10 (awake all night), please rate how much your sleep was disturbed by itch last night.	From baseline to week 12
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12	Subjects were asked the following question to determine their duration of itching: Over the last 12 hours approximately how many hours, if any, did you itch?	From baseline to week 12
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12	Subjects were asked to rate their itch over the last 12 hours using a list of adjectives describing different levels of symptom intensity: Over the last 12 hours how would you rate your itch? No itch; Mild; Moderate and Severe; Pruritus was evaluated by the subject, using the eDiary, twice daily for 1 week prior to the start of study treatment (run-in period) and during treatment (baseline to Day 84).	From baseline to week 12

Collaborators and Investigators

• Sponsor: Ziarco Pharma Ltd
• Investigators: Study Director: Study Director, Novartis

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2016
• Primary Completion (Actual): December 22, 2016
• Study Completion (Actual): December 22, 2016

Study Registration Dates

• First Submitted: November 27, 2015
• First Submitted That Met QC Criteria: November 27, 2015
• First Posted (Estimate): December 1, 2015

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: ZPL389/102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No