Study to Determine the Efficacy, Safety and Tolerability of Once Daily Oral ZPL-3893787-18 in Adult Subjects with Moderate to Severe Plaque Psoriasis.

Phase 1

Active, not recruiting

• Conditions: PLAQUE PSORIASIS; MedDRA version: 18.1Level: LLTClassification code 10071117Term: Plaque psoriasisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2015-003812-19-BG
• Lead Sponsor: Ziarco Pharma Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-04
• Last Update Posted: 9 October 2017

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for inclusion in the study
1. A documented history of moderate to severe plaque psoriasis for at least 6 months prior to screening.
2. Male or female, aged =18 years.
3. Females should be either of non-child-bearing potential or must agree to use highly effective methods of contraception. Males with partners who are WOCBP must also use contraception.
4. Body weight of = 50 kg.
5. Body Mass Index of =34.9 kg/m2.
6. Psoriasis Area and Severity Index (PASI) =10 at both Screening and Day 0.
7. An Investigator’s Global Assessment (IGA) score = 3 at both Screening and Day 0.
8. Psoriasis affecting =10% BSA at Screening and Day 0.
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, diary completion and other study procedures.
10. Willing to avoid exposure to sun, UVA or UVB from screening until completion of the follow up visit.
11. Evidence of a personally signed and dated informed consent form, indicating that the subject has been informed of all pertinent aspects of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Subjects presenting with any of the following will not be included in the study:
1. 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.
2. Biologic treatments for psoriasis (e.g. Enbrel, Humira, Stelara, Cosentyx) within 3 months of the start of the Run-In.
3. Phototherapy (e.g. UVA, UVB, PUVA) within 4 weeks of the start of the Run-In.
4. Oral calcineurin inhibitors and immunosuppressants (e.g. cyclosporine, azathioprine, methotrexate) within 4 weeks of the start of the Run-In.
5. Systemic corticosteroids within 4 weeks of the start of the Run-In.
6. Oral antihistamines and leukotriene inhibitors and tricyclic antidepressants within 1 week of the start of the Run-In.
7. 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.
8. Subjects who are using any concomitant medication(s) that in the investigators’ opinion could affect psoriasis (e.g. ß-blockers, lithium) within the 3 months prior to the start of the Run-In.
9. Potent CYP1A inhibitors (e.g. ciprofloxacin, enoxacin, fluvoxamine) from the start of the Run-In.
10. Evidence of significant concomitant clinical disease that may need a change in management during the study or could interfere with the conduct or safety of this study (Stable well-controlled chronic conditions such as controlled hypertension (BP<140/90 mmHg) thyroid disease, well-controlled Type 1 or Type 2 diabetes (HbA1c< 8%), hypercholesterolemia, gastroesophageal reflux, or depression under control with medication (other than tricyclic antidepressants), are acceptable provided the symptoms and medications would not be predicted to compromise safety or interfere with the tests and interpretations of this study).
11. Clinically significant cardiac disease or ECG abnormalities, including:
• Predominant heart rhythm other than normal sinus rhythm
• AV block greater than first degree
• Resting heart rate >100 or <50 bpm
• Electrocardiographic evidence or a history of myocardial infarction
• Electrocardiographic evidence of conduction system abnormality
• Subjects with pre-randomization evidence of QTcF prolongation (defined as >450 msec)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of an oral 30 mg dose of ZPL-3893787-18 when administered once daily, for 12 weeks, to subjects with moderate to severe plaque psoriasis.;Secondary Objective: To evaluate the safety and tolerability of 12 weeks treatment of once daily oral ZPL-3893787-18 (30 mg), in subjects with moderate to severe plaque psoriasis.<br>To evaluate the ability of 12 weeks treatment of once daily oral ZPL-3893787-18 (30 mg) to reduce pruritus in subjects with moderate to severe plaque psoriasis.<br>;Primary end point(s): Percentage change from baseline in PASI score.;Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • PASI-75 response: Defined as a =75% reduction from baseline in PASI score <br>• PASI 50 response: Defined as a =50% reduction from baseline in PASI score <br>• Improvement in IGA (5-point IGA scale), defined as a reduction of at least 2 categories from baseline<br>• Change from baseline in the daytime NRS for pruritus (worst itch) <br>• Change from baseline in the night time NRS for pruritus (worst itch) <br>• Change from baseline in the NRS for sleep disturbance <br>• Change from baseline in duration of itching <br>• Change from baseline in the verbal rating score (VRS) for pruritus ;Timepoint(s) of evaluation of this end point: Week 12