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

• ClinicalTrials.gov Identifier: NCT02618616
• Recruitment Status: Completed
• First Posted: December 1, 2015
• Results First Posted: July 20, 2021
• Last Update Posted: July 20, 2021
• Sponsor: Ziarco Pharma Ltd
• Information provided by (Responsible Party): Ziarco Pharma Ltd

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Psoriasis	Drug: ZPL-3893787; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 11, 2016
• Actual Primary Completion Date: December 22, 2016
• Actual Study Completion Date: December 22, 2016

Arms and Interventions

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 Name: ZPL389
Placebo Comparator: Placebo; Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Psoriasis Assessment of Severity Index (PASI) at Week 12 [ Time Frame: From baseline to 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.

Secondary Outcome Measures :

1. PASI-50 and PASI-75 Responders at Week 12 [ Time Frame: From baseline to week 12 ]
   PASI-75 and PASI-50 are defined as a 75% and 50% reduction, respectively, from baseline in PASI score at Week 12.
2. Improvement in Investigator Global Assessment (IGA) at Week 12 [ Time Frame: From baseline to 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.
3. Change From Baseline in the Numerical Rating Scale (NRS) for Pruritus (Worst Itch) at Week 12 [ Time Frame: From baseline to 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.
4. Patient Global Impression of Change (PGIC) a Week 12 [ Time Frame: From baseline to 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:

   1. Very much improved
   2. Much improved
   3. Minimally improved
   4. No change
   5. Minimally worse
   6. Much worse
   7. Very much worse
5. Change From Baseline in Body Surface Area (BSA) and Percentage Change From Baseline at Week 12 [ Time Frame: From baseline to 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.
6. Change From Baseline in the Daytime and Night Time NRS for Pruritus (Worst Itch) at Week 12 [ Time Frame: From baseline to 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.
7. Change From Baseline in the NRS for Sleep Disturbance at Week 12 [ Time Frame: From baseline to 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.
8. Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 [ Time Frame: From baseline to 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?
9. Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 [ Time Frame: From baseline to 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).

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Belgium

Belgium Study Centre

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

Germany

German Study Centre

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

Poland

Polish Study Centre

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

United Kingdom

UK Study Centre

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

Sponsors and Collaborators

Ziarco Pharma Ltd

Investigators

• Study Director: Study Director; Novartis

More Information

• Responsible Party: Ziarco Pharma Ltd
• ClinicalTrials.gov Identifier: NCT02618616
• Other Study ID Numbers: ZPL389/102
• First Posted: December 1, 2015
• Results First Posted: July 20, 2021
• Last Update Posted: July 20, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases