| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate-to-Severe Plaque Psoriasis |
|
| 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 | 18.0 |
| 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 |
| The coprimary objectives of the study are to test whether ixekizumab Q2W/Q4W is superior to FAE and is superior to MTX at Week 24 in the treatment of patients with moderate-to-severe psoriasis who are candidates for systemic therapy as measured by 75% improvement in Psoriasis Area and Severity Index (PASI 75) from baseline assuming, that non-adherent patients are treatment failures. |
|
| E.2.2 | Secondary objectives of the trial |
To assess whether ixekizumab is superior to FAE and is superior to MTX over the course of treatment in the treatment of patients with moderate-to-severe psoriasis who are candidates for systemic therapy assuming that non-adherent patients are treatment failures as measured by efficacy outcomes
To assess whether ixekizumab is superior to FAE and superior to MTX at all study visits in the treatment of patients with moderate-to-severe psoriasis assuming that non-adherent patients are treatment failures as measured by health outcomes assessments
To explore the treatment difference between MTX and FAE with respect to the same outcomes as described above.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Present with moderate-to-severe chronic plaque psoriasis based on a diagnosis of chronic psoriasis for at least 6 months before baseline (Week 0; Visit 2), as determined by the investigator
[2] Patients who are candidates for systemic therapy, and who are naive to systemic treatment for psoriasis.
[3] Have a PASI score ≥10 and BSA ≥10 at screening (Visit 1) and at baseline (Week 0, Visit 2)
[4] Are male or female patients of 18 years or older
[5] If a male patient, agree to use a reliable method of birth control during the study and for at least 6 month following the last dose of investigational product. Male patients should not donate sperm during this period.
[6] If a female patient of childbearing potential, must test negative for pregnancy and agree to use a reliable method of birth control or remain abstinent during the study and for at least 15 weeks following the last dose of investigational product. Methods of contraception considered acceptable include oral contraceptives, contraceptive patch, intrauterine device, vaginal ring, diaphragm with contraceptive gel, or condom with contraceptive gel
[7] For non-childbearing potential female patients, patients must be:
women who have had surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation),
-or-
women who are ≥60 years of age,
or-
women ≥40 and <60 years of age who have had a cessation of menses for ≥12 months and a follicle-stimulating hormone (FSH) test confirming non–childbearing potential (≥40 mIU/mL)
[8] Have a chest x-ray or results from chest x-ray obtained within 6 months before screening visit
[9] Have given written informed consent approved by Lilly, or its designee, and the Institutional Review Board (IRB)/ERB governing the site
|
|
| E.4 | Principal exclusion criteria |
10 Have predominant pattern of pustular, erythrodermic, and/or guttate forms of psoriasis
11 Have a history of drug-induced psoriasis
12 Have received systemic nonbiologic psoriasis therapy
13 Have received natalizumab, or other agents targeting α 4 integrin
14 Have received phototherapy within 4 weeks of baseline or have had topical psoriasis treatment within 2 weeks of baseline
15 Exceptions: low potency to mild potency topical steroids will be permitted for use limited to the face, axilla, groin and/or genitalia Have prior, concurrent, or recent use of ixekizumab or any other biological psoriasis therapy
16 Have any condition or contraindication as addressed in the local labeling for methotrexate or FAE that would preclude the patient from participating
18 Have had a live vaccination within 12 weeks of baseline, or intend to have a live vaccination during the course of the study or within 15 weeks of completing treatment in this study, or have participated in a vaccine clinical study within 12 weeks of baseline
19 Have had a vaccination with BCG within 12 months of baseline or intend to have vaccination with BCG during the course of the study or within 12 months of completing treatment in this study
20 Have a known allergy or hypersensitivity to any biologic therapy that would pose an unacceptable risk to the patient
22 Have had any major surgery within 8 weeks of baseline or will require surgery during the study that would pose an unacceptable risk
23 Have active or history of malignant disease within 5 years prior to baseline
24 Presence of significant uncontrolled cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic, or neuropsychiatric disorders or abnormal laboratory values at screening that pose an unacceptable risk to the patient or of interfering with the interpretation of data
25 Have ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the patient
26 Presence of significant uncontrolled neuropsychiatric disorder, have history of a suicide attempt, have a score of 3 on Item 12 (Thoughts of Death or Suicide) of the QIDS-SR16 at screening or baseline or are clinically judged by the investigator to be at risk for suicide
27 Have evidence or suspicion of active or latent TB
28 Have a known immunodeficiency
29 Are positive for human immunodeficiency virus serology
30 Have evidence of or test positive for HBV by testing positive for anti-hepatitis B core antibody and HBV DNA positive
31 Have evidence of or test positive for hepatitis C virus.
32 Have a body temperature ≥38°C at baseline, these patients may be re screened (1 time) ≥4 weeks after documented resolution of elevated temperature.
34 Have severe gastrointestinal disease, oral ulcer, or known, active gastrointestinal ulcer
35 Are women who are planning to become pregnant, who are pregnant, or who are breast feeding
36 Have had a serious infection, have been hospitalized, or have received intravenous antibiotics for an infection within 12 weeks of baseline; have had a serious bone or joint infection within 24 weeks of baseline, or have ever had an infection of an artificial joint; or are immunocompromised to an extent such that participation in the study would pose an unacceptable risk
37 Have or have had an infection typical of an immunocompromised host and/or that occurs with increased incidence in an immunocompromised host
38 Have or have had a herpes zoster infection or any other clinically apparent varicella-zoster virus infection within 12 weeks of baseline
39 Have had any other active or recent infection within 4 weeks of baseline that would pose an unacceptable risk to the patient; these patients may be re screened (1 time) ≥4 weeks after documented resolution of symptoms
40 At screening have a total WBC count <3000 cells/μL (<3.00x103/L or <3.00 GI/L)
41 At screening have a neutrophil count <1500 cells/μL (<1.50x103/L or <1.50 GI/L)
42 At screening have a lymphocyte count <800 cells/μL (<0.80x103/L or <0.80 GI/L)
43 At screening have a platelet count <100 000 cells/μL (<100x103/L or <100 GI/L)
44 At screening have hemoglobin <8.5 g/dL for male patients and <8.0 g/dL for female patients
45 At screening have AST or ALT >2.5 times (x) the upper limit of normal
46 At screening have ALP >3xULN or ALP >2.5xULN and total bilirubin >2xULN
47 At screening have clinical laboratory test results that are outside the normal reference range for the population and are considered clinically significant, per investigator assessment
48 At screening, have a creatinine clearance (≤80 mL/min, using Cockcroft Gault formula)
49 At screening patients with significant, present, or early liver disease, eg, explained by alcohol consumption or hepatic insufficiency
50 Cannot avoid excessive sun exposure or use of tanning booths for at least 4 weeks before baseline and during the study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| 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 | No |
| 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) | 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 20 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
|
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 3 |
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