| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe chronic plaque-type psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic plaque-type psoriasis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| 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 four dose regimens of M1095 compared to placebo on achievement of an Investigator’s Global Assessment (IGA) score of 0 or 1 after 12 weeks of treatment in subjects with moderate to severe chronic plaque-type psoriasis. |
|
| E.2.2 | Secondary objectives of the trial |
. To evaluate the efficacy of four dose regimens of M1095 compared to placebo during a 12-week treatment period on secondary endpoints: Psoriasis Area Severity Index (PASI) 75, PASI 90, PASI 100, change in PASI and change in IGA.
· To assess the dose-regimen efficacy relationship for M1095 after 12, 24, 36, and 48 weeks of treatment.
· To evaluate the longer-term efficacy of M1095 at Week 24 and at Weeks 36 and 48.
· To assess the safety and tolerability of M1095.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Ambulatory male and female subjects between 18 and 75 years of age at time of consent.
2. Subject has had stable moderate to severe plaque-type psoriasis for at least 6 months prior to randomization (e.g. no morphology changes or significant flares of disease activity in the opinion of the investigator).
3. Subject must be considered, in the opinion of the investigator, not adequately controlled by photo, topical or previous systemic treatments and a candidate for systemic biologic therapy.
4. Subject has IGA ≥3, involved body surface area (BSA) ≥10% and PASI ≥12 at screening and at baseline.
5. Subject is in the opinion of the investigator able to comply with the study procedures.
6. Following verbal and written information about the study, subject must provide signed and dated informed consent before any study related activity is carried out. |
|
| E.4 | Principal exclusion criteria |
1. Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, or other skin conditions at the time of the screening visit (e.g., eczema) that would interfere with evaluations of psoriasis (Note: psoriatic arthritis is NOT exclusionary.)
2. Subject has drug-induced psoriasis.
3. Other medical conditions:
a. At the time of consent, subject has a planned in-patient surgical intervention between baseline and the Week 52 evaluation.
b. Subject has an active infection or history of infections as follows:
i. Any active infection for which systemic anti-infectives were used within 28 days prior to randomization.
ii. A serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to randomization.
iii. Any history of bone infection requiring surgical intervention and/or intravenous antibiotics.
iv. Recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject.
c. Subject has a known history of active tuberculosis.
d. Subject has a positive QuantiFERON®-TB Gold test for tuberculosis at screening.
e. Subject has an underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator places the subject at unacceptable risk for receiving an immunomodulatory therapy.
f. Subject has known history of inflammatory bowel disease.
g. Subject with known chronic liver disease or tests positive for hepatitis B virus (HBV) infection or has antibodies to hepatitis C virus (HCV) at screening.
h. Subject has antibodies to human immunodeficiency virus (HIV) at screening.
i. Subject has history of heart failure, myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization.
j. Subject has uncontrolled hypertension characterized by two blood pressure measurements separated by at least 15 minutes with systolic >160mmHg or diastolic >100mmHg.
k. Subject has clinically significant electrocardiogram (ECG) abnormalities on centrally read ECG.
l. Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
m. Subject has history of malignancy within 5 years EXCEPT cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma which has been treated and considered cured.
n. Subject has any concurrent medical condition that, in the opinion of the investigator, could cause this study to be detrimental to the subject.
4. Subject has laboratory abnormalities at screening, including any of the following:
a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x the upper limit of normal (one retest is allowed for aminotransferase abnormalities.)
b. Serum direct bilirubin >1.5 mg/dL.
c. White blood cell (WBC) count <3.00 x 103/µL.
d. Absolute neutrophil count <1.50 x 103/µL.
e. Absolute lymphocyte count <0.50 x 103/µL.
f. Platelet count <100,000/µL.
g. Calculated creatinine clearance (via Cockcroft Gault) of <30 mL/min.
h. Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results.
5. Subject has used topical therapy (details available in the Protocol).
6. Subject has used the following within 28 days of randomization: ultraviolet A (UVA) light therapy (with or without psoralen ; UVB light therapy; excimer laser; oral retinoids; methotrexate; cyclosporine; systemically administered calcineurin inhibitors; azathioprine; thioguanine; hydroxyurea; cyclophosphamide; fumarates; or oral or parenteral corticosteroids including intramuscular or intraarticular administration (exception: otic, nasal, ophthalmic, or inhaled corticosteroids within recommended doses is permitted); other non-biologic systemic therapy for psoriasis.
7. Subject is not willing to limit ultraviolet (UV) light exposure (e.g. sunbathing and/or the use of tanning devices) during the study.
8. Subject has received live vaccine(s) within 6 weeks of randomization.
9. Subject has received prior treatment at any time before screening with any compound (marketed or investigational) targeting IL-17 (i.e. direct inhibitor, receptor blocker, etc.).
10. Subject has received prior treatment at any time before screening with more than 2 biologic therapies (ustekinumab, TNF targeting therapies, or investigational therapies).
11. Subject has received TNF targeting therapies in the 12 weeks prior to randomization, ustekinumab in the 6 months prior to randomization, or investigational biological therapies within 12 weeks, or within 5 half lives of randomization, whichever is the longer.
Exclusion criteria no. 12 to 22 can be found in the study Protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| IGA score of 0 or 1 at Week 12, with an IGA reduction of at least 2 points from baseline. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
. PASI 75 at Week 12.
. PASI 100 at Week 12.
. PASI 75 and PASI 100 beyond Week 12.
. PASI 90 responses.
. Change from baseline in PASI and in IGA scores.
Safety:
Adverse events, skin evaluation, laboratory assessments, vital signs, ECGs, drug discontinuations, and instruments to assess depression and suicidality [electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) and Personal Health Questionnaire Depression Scale (PHQ-8)].
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 52 Final Safety and Efficacy Assessments |
|
| 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 | Yes |
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | No |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| 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 | 41 |
| 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 |
| Canada |
| Czech Republic |
| Germany |
| Hungary |
| Poland |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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