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 Plaque Psoriasis (reoccurring disease of the immune system with symptoms such as red patches on the skin commonly found with silvery scale, pain, itching and bleeding). |
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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 | 17.0 |
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 |
To evaluate the safety and tolerability of three dose levels of MT-1303 in subjects with moderate to severe chronic plaque psoriasis.
To evaluate the efficacy of three dose levels of MT-1303 in subjects with moderate to severe chronic plaque psoriasis compared to placebo after 16 weeks of treatment on Psoriasis Area and Severity Index (PASI). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of three dose levels of MT-1303 in subjects with moderate to severe chronic plaque psoriasis compared to placebo on clinical outcomes (Physician Static Global Assessment [PGA], body surface area [BSA], Nail Psoriasis Severity Index [NAPSI]).
To evaluate the efficacy of three dose levels of MT-1303 on quality of life as measured by Dermatology Life Quality Index (DLQI).
To evaluate the dose-response relationship of three dose levels of MT-1303 in subjects with moderate to severe chronic plaque psoriasis.
To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of three dose levels of MT-1303 and its active phosphorylated metabolite (MT-1303-P). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female 18 to 65 years (limits included) of age at the time of signing the informed consent form.
2. Able to provide written informed consent and to comply with the requirements of the protocol.
3. Have been diagnosed with plaque psoriasis for at least 6 months prior to screening.
4. Have moderate to severe chronic plaque psoriasis as defined by PASI score ≥ 12 and BSA ≥ 10% at baseline.
5. In the investigator's opinion is a candidate for systemic therapy.
6. For male and females of reproductive potential, two methods of contraception must be used throughout the study and for 12 weeks after cessation of study medication. At least one of the methods of contraception must be a barrier method.
All males who have not been sterilised (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) and females who do not meet the criteria for non-child-bearing potential are considered to have reproductive potential. For females, non-child-bearing potential is defined as either at least 2 years post-menopausal or permanently sterilised, e.g., by bilateral tubal occlusion, hysterectomy or bilateral salpingectomy.
7. Presence of antibodies (immunoglobulin G [IgG]) to Varicella Zoster Virus (VZV) at screening.
8. Negative results for both QuantiFERON-TB Gold test and chest X-ray (with no evidence of tuberculosis [TB]) at screening. Note: if the chest X-ray has been done in the past 6 months prior to screening, no repeat is necessary. Urine pregnancy test to be obtained and results negative prior to chest X-ray. |
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E.4 | Principal exclusion criteria |
1.Non-plaque forms of psoriasis (e.g., guttate, erythrodermic or pustular)
2.Current drug-induced or aggravated psoriasis
3.Pregnancy, lactation or a positive serum beta human chorionic gonadotropin (hCG) level measured during screening or at baseline, or intention to become pregnant or to breast-feed during the course of the study
4.History of cardiovascular diseases as stated in the protocol
5.Known high risk for QT/QTc prolongation such as a family history of long QT syndrome or sudden death
6.Low heart rate (< 50 bpm) at screening or baseline (measured using 12-lead electrocardiogram [ECG])
7.History or known presence of cerebrovascular diseases or ischaemia of the spinal cord
8.Significant, uncontrolled disease such as respiratory (including chronic, obstructive pulmonary disease), renal, hepatic, endocrine and gastrointestinal disease
9.Subjects who are currently treated for autoimmune disorders other than psoriasis
10.History of cancer, in the last 5 years, including both solid tumour and haematological malignancies, but excluding basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved
11.Known active bacterial, viral, fungal or mycobacterial infection or any major episode of infection requiring hospitalisation or treatment with intravenous antibiotics within 28 days prior to randomisation or oral antibiotics within 14 days prior to randomisation
12.Known history of recurrent or chronic infection such as TB, hepatitis B, hepatitis C, human immunodeficiency virus or syphilis
13.Any documented history or diagnosis of diabetes mellitus (Type I or II)
14.Any significant eye disorder such as macular oedema, uveitis or evolutive retinopathy
15.History of, or currently active, primary or secondary immunodeficiency
16.Documented organ transplantation
17.History of alcohol abuse within 5 years prior to screening and any history of solvent and/or drug abuse
18.Previous exposure to fingolimod or to any other S1P receptor modulator (investigational products)
19.Known history of allergy, hypersensitivity or any serious reaction to any component of the study medication (i.e., mannitol, gelatine)
20.Previous treatment with any investigational agent within 3 months prior to randomisation or five half-lives of the investigational product, whichever is the longer
21.Receipt of a live vaccine within 28 days prior to randomisation
22.Have received systemic immunosuppressive agents (e.g., tacrolimus) within 4 weeks prior to randomisation
23.Have received disease modifying anti-rheumatic drugs (DMARDs) within 4 weeks prior to randomisation
24.Topical therapy that could, in the opinion of the Investigator, affect psoriasis or PASI evaluation within 2 weeks prior to randomisation
25.Any systemic medications or treatments (other than biologics) that affect psoriasis or PASI evaluation including, but not limited to, oral or injectable corticosteroids, psoralens, sulfasalazine, hydroxyurea, fumaric acid esters derivatives within 4 weeks prior to randomisation
26.Systemic retinoids, 1,25 dihydroxy vitamin D3 and analogues at doses that might, in the opinion of the Investigator, affect psoriasis and PASI evaluation within 4 weeks prior to randomisation. However, vitamin/multivitamin supplements taken at doses at or around the recommended daily dose (RDA) are allowed
27.Have used phototherapy within 4 weeks prior to randomisation
28.Have used infliximab, adalimumab, etanercept or ustekinumab within 12 weeks prior to randomisation
29.Currently receiving lithium carbonate or have received lithium carbonate within 4 weeks prior to randomisation
30.Subject not willing to avoid excess sun exposure during the study duration
31.Need for, or likely need for, treatment with Class I or Class III anti-arrhythmic drugs or with heart-rate-lowering beta-blockers or calcium-channel blockers (e.g., verapamil or diltiazem), or with any other drugs which can reduce the heart rate (e.g., ivabradine)
32.Need for, or likely need for, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) except for subjects with psoriatic arthritis (PsA).
33.Platelet count < 100,000/µL at screening
34.Haemoglobin < 10.0 g/dL at screening
35.White cell count < 3500/µL at screening
36.Lymphocyte count < 800/µL at screening
37.Glycosylated haemoglobin (HbA1c) > 6.5% at screening
38.Liver function tests (aspartate transaminase [AST] or alanine transaminase [ALT]) ≥ 2 x upper limit of normal (ULN) at screening
39.Clinically significant findings on 12-lead ECG (at screening or baseline) and/or Holter ECG (at screening) that the Investigator considers may jeopardise the subject’s health, e.g., acute ischaemia
40.Corrected QT-interval using Fridericia’s formula (QTcF) interval ≥ 480 ms for females and ≥ 460 ms for males in 12-lead ECG at screening or baseline
41.Body mass index > 40 kg/m2 at screening
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who achieve PASI 75 (at least 75% reduction from baseline) at Week 16. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various time points throughout the study - please refer to the detailed 'Time and Events Schedule' table in the protocol for full details. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints:
• Proportion of subjects who achieve PASI 90 (at least 90% reduction from baseline in PASI score) at Weeks 4, 8, 12 and 16.
• Proportion of subjects who achieve PASI 50 (at least 50% reduction from baseline in PASI score) at Weeks 4, 8, 12 and 16.
• Proportion of subjects who achieve PASI 75 at Weeks 4, 8 and 12.
• Mean percent change from baseline in PASI score at Weeks 4, 8, 12 and 16.
• Mean percent change from baseline in PGA at Weeks 4, 8, 12 and 16.
• Mean percent change from baseline in NAPSI score of the worst affected fingernail at Week 16.
• Quality of life as measured by DLQI at Weeks 4, 8, 12 and 16.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various time points throughout the study - please refer to the detailed 'Time and Events Schedule' table in the protocol for full details. |
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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 | 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 |
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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) | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
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 |
Estonia |
Germany |
Hungary |
Latvia |
Poland |
Russian Federation |
Ukraine |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |