E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-to-Severe Chronic Plaque Psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate-to-Severe Chronic Plaque Psoriasis |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071117 |
E.1.2 | Term | Plaque psoriasis |
E.1.2 | System Organ Class | 100000004858 |
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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 |
Primary Efficacy Objective: To assess the efficacy of SCH 900222/MK-3222, hereafter referred to as MK-3222, compared to placebo in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area and Severity Index from baseline (PASI 75 response) and the proportion of subjects with a Physician’s Global Assessment (PGA) score of “clear” or “minimal” with at least a 2 grade reduction from baseline at Week 12.
Primary Safety/Tolerability Objective: To assess the safety/tolerability of MK-3222 in subjects with moderateto-severe chronic plaque psoriasis at Week 12.
Extension Study: To assess long-term safety/tolerability of MK-3222 in subjects with moderate-to-severe
chronic plaque psoriasis over 4 years. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of MK-3222 compared to etanercept in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75 response) and the proportion of subjects with a Physician’s Global Assessment (PGA) score of “clear” or “minimal” with at least a 2 grade reduction from baseline at Week 12, and from baseline at week 28. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetic Study: The DNA samples collected in the current trial will be used to study various genetic causes for how subjects may respond to a drug. The DNA samples will be stored to provide a resource for future studies conducted by the Sponsor
focused on the study of genes responsible for how a drug enters and is removed by the body, how a drug works, other pathways a drug may interact with, or other aspects of disease. |
Las muestras de ADN recogidas en el presente ensayo se utilizarán para estudiar diversas causas genéticas de cómo pueden responder los sujetos a un medicamento. Las muestras de ADN se conservarán para proporcionar recursos destinados a futuros estudios que realice el promotor, centrándose en el estudio de genes responsables del mecanismo por el que un medicamento penetra en el organismo y es eliminado de él, en el modo de actuar de un medicamento, en otras vías por las que un medicamento podría establecer interacciones o en otros aspectos de la enfermedad |
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E.3 | Principal inclusion criteria |
1. Subject must be >or=18 years of age.
2. Diagnosis of predominantly plaque psoriasis for >or= 6 months (as determined by subject interview and confirmation of diagnosis through physical examination by investigator).
3. Subject is considered to be a candidate for phototherapy or systemic therapy.
4. Psoriasis BSA involvement >or=10% at baseline (Visit 2).
5. PASI score >or=12 at baseline (Visit 2).
6. PGA of at least moderate disease (>or=3) at baseline (Visit 2).
7. No history of untreated latent or active tuberculosis (TB) prior to Screening, signs or symptoms suggestive of active TB upon medical history and/or physical examination, and no recent close contact with a person with active TB. (See protocol for more details about this criteria).
8. Subject is unlikely to conceive.
9. For women of childbearing potential, a negative serum pregnancy test at
10. Screening and a negative urine pregnancy test within 24 hours prior to the first dose of study medication.
11. Clinical laboratory tests within the following parameters prior to the first dose of study medication:
ALT, AST, or alkaline phosphatase <or=1.5xULN
Creatinine <or=1.5 mg/dL (or < 133 μmol/L)
Hemoglobin ≥10 g/dL
Absolute neutrophil count >or=1500/mm3
Platelet count >or=100,000/mm3.
12. Physical examination within clinically acceptable limits.
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E.4 | Principal exclusion criteria |
1. Subject has predominantly non-plaque forms of psoriasis specifically
erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new-onset guttate psoriasis.
2. Subject had previously used etanercept.
3. Subject with current or history of, severe psoriatic arthritis and is well-controlled on current therapy.
4. Subject who is expected to require topical therapy, phototherapy, or systemic therapy for psoriasis during the trial.
5. Presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or severe infection (eg, pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to Screening.
6. Women of childbearing potential who are pregnant, intend to become pregnant (within 6 months of completing the trial), or are lactating.
7. Positive human immunodeficiency virus (HIV) test result, hepatitis B surface antigen (HBsAG), or hepatitis C virus (HCV) test result.
8. Prior malignancy or concurrent malignancy (excluding successfully treated basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma with no evidence of recurrence within 5 years or carcinoma in situ of the cervix that has been adequately treated).
9. Subject who has received live viral or bacterial vaccination within 4 weeks prior to baseline or who intends to receive live viral or bacterial vaccination during the trial.
10. Within 6 months prior to Screening, any significant organ dysfunction or clinically significant laboratory abnormalities that place the subject at unacceptable risk for participation in a trial of an immunomodulatory therapy in the judgment of the investigator.
11. Hospitalization due to an acute cardiovascular event, cardiovascular illness or cardiovascular surgery within 6 months of screening.
12. Subject has sustained, uncontrolled hypertension (systolic blood pressure of
>or= 160 mm Hg and/or diastolic blood pressure of >or= 100 mm Hg at screening), or has uncontrolled diabetes.
13. Subject who, in the opinion of the investigator, has a history of alcohol or drug abuse in the previous year.
14. Subject is sensitive or allergic to latex.
15. Subject with any previous use of MK-3222 or other IL-23/Th17 pathway inhibitors, including p40, p19 and IL-17 antagonists.
16. Subject who has received any of the medications listed in Table 1 of the protocol within the indicated washout period prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint
- Proportion of subjects with PASI 75 response at Week 12
- Proportion of subjects with a PGA score of “clear” or “minimal” with at least a 2 grade reduction from baseline at Week 12 |
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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) |
Key Secondary Efficacy Endpoints
- Proportion of subjects with PASI 75 response at Week 28
- Proportion of subjects with a PGA score of “clear” or “minimal” with at least a 2 grade reduction from baseline at Week 28.
Other Secondary Efficacy Endpoints
Proportion of subjects with PASI 90 response at Weeks 12 and 28
Proportion of subjects with PASI 100 response at Weeks 12 and 28
Change in DLQI from baseline at Weeks 12 and 28
Proportion of subjects with a DLQI score of 0 or 1 at Weeks 12 and 28
Change and percent change from baseline in PASI score over time
Change in the nail psoriasis severity index (NAPSI) from baseline at Week 12 and Week 28 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Subjects on placebo will start on active treatment after week 12. |
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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 | 4 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Spain |
Switzerland |
Taiwan |
Ukraine |
United Kingdom |
United States |
Croatia |
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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
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |