E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071117 |
E.1.2 | Term | Plaque psoriasis |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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.
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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. β-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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change from baseline in PASI score. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• PASI-75 response: Defined as a ≥75% reduction from baseline in PASI score
• PASI 50 response: Defined as a ≥50% reduction from baseline in PASI score
• Improvement in IGA (5-point IGA scale), defined as a reduction of at least 2 categories from baseline
• Change from baseline in the daytime NRS for pruritus (worst itch)
• Change from baseline in the night time NRS for pruritus (worst itch)
• Change from baseline in the NRS for sleep disturbance
• Change from baseline in duration of itching
• Change from baseline in the verbal rating score (VRS) for pruritus |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Poland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |