E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Plaque Psoriasis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe 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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050576 |
E.1.2 | Term | Psoriasis vulgaris |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 |
Safety Objective: To examine the safety and tolerability of 12 weeks’ treatment with VB-201 or placebo in patients with psoriasis.
Efficacy Objective:To examine the effect of 12 weeks’ treatment with two different doses of VB-201 compared to placebo on measures of disease activity in patients with psoriasis.
Exploratory Biomarker and RNA Expression Objectives
• To examine the effect of 12 weeks treatment with two different doses of VB-201 as compared with placebo on inflammatory related biomarkers.
• To examine the effect of 12 weeks treatment with two different doses of VB-201 as compared with placebo on RNA expression of inflammation related genes.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Fully understand all elements of and have signed and dated the written Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent before initiation of protocol-specified procedures;
2. Male or female Patients, ≥18 to ≤75 years of age, who have a diagnosis of chronic plaque psoriasis for at least 6 months;
3. Non-anorexic subjects with a BMI ≥20;
4. Psoriasis Area and Severity Index (PASI) score of ≥12;
5. Plaque psoriasis covering ≥10% of body surface area (BSA);
6. Psoriasis severity at least moderate, scoring at least 3 on a 0 to 5 point Physician Global Assessment (PGA) scale;
7. For a female subject; either:
- subject is of non-childbearing potential, defined as: menopause with amenorrhea >2 years, hysterectomy, or bilateral oopherectomy
or
- agrees to continue to use adequate contraception (implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence or vasectomised partner) throughout the study and for at least one month following termination and have a negative pregnancy test at screening and before the first dose of study drug;
Males must use at least one method of contraception (e.g., condom) throughout the study;
8. In the opinion of the investigator, the subject will be compliant and have a high probability of completing the study and all required procedures.
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E.4 | Principal exclusion criteria |
1. The subject presents with the predominant type of psoriasis as guttate, erythrodermic, inverse, pustular or palmo-plantar or an unstable form of psoriasis;
2. Received any investigational drug within 30 days of screening;
3. The subject has not undergone wash-out periods of sufficient duration for the following treatments at Baseline:
• Topical psoriasis treatments: 2 weeks
• Systemic psoriasis treatments: 4 weeks or 5 half-lives (whichever is longer);
• Phototherapy: 4 weeks
4. The subject anticipates getting enough ultra-violet light during the study (e.g. sunbathing; tanning salon, etc.) to cause psoriasis to improve;
5. The subject has a known allergy or sensitivity to the study treatment(s) or to any of the excipients contained in the study drug formulation (see list of ingredients in the Investigator’s Brochure);
6. Any other acute or chronic medical condition that, in the opinion of the investigator, increases the risk to the subject or the likelihood that the subject will be unable to complete the study;
7. Patients with any laboratory test at screening that common medical practice would deem as significantly abnormal. The following will be deemed as significantly abnormal:
• alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase ≥1.5 times the upper limit of normal (ULN) or
• cytopenia (to include any of the following: WBC <3.5x1000/μL; Hgb <10 g/dL; platelets <120x1000/μL; neutrophils absolute <1.5x1000/μL; lymphocytes absolute <0.8x1000/μL) or
• Creatinine ≥1.25 times the upper limit of normal (ULN);
If, in the investigator’s opinion, there is no reason for the test result(s) to be abnormal, the abnormal test(s) may be repeated once during the screening period.
8. History of cancer, the exception is skin cancer, see below.
• Patients with >3 previous squamous cell skin cancer lesions are excluded
• Patients who had histologically controlled excision of basal cell and/or squamous cell carcinoma of the skin and have been declared to have no evidence of tumor can be enrolled
• Patients who had basal cell and/or squamous cell carcinoma of the skin removed and have not met these criteria can be enrolled if the skin cancer was removed >3 years prior to study participation and there is no evidence of recurrence;
9. Has a clinically significant systemic infection (e.g., chronic or acute infection, UTI, URI) within 30 days of Day 0, or a history or presence of recurrent or chronic infection (e.g. viral infections, [including hepatitis B or C, HIV], bacterial infections, systemic fungal infections, or syphilis);
10. Evidence of tuberculosis as indicated by a positive tuberculin skin test (defined as ≥10 mm induration) or a quantiferon test in subjects known to have a + PPD and a negative chest x-ray at screening or prior to screening;
11. History of substance abuse, including alcohol abuse, within the past year;
12. Has a history of or has a current, clinically significant major psychiatric disorder (e.g., major depressive disorder, psychosis, schizophrenia) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV TR) [Exception; Patients with depression that has been adequately controlled for at least 6 months may enroll in the study];
13. History of clinically significant hypoglycemia;
14. Subjects with currently active peptic ulcer or gastroesophageal reflux disease;
15. Female subject with a positive pregnancy test or nursing, or planning a pregnancy during the course of the study;
16. Unwillingness to use reliable and acceptable contraceptive methods (e.g. implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence or vasectomised partner) throughout the study and for at least one month following termination, except for female patients who are surgically sterile (post hysterectomy or at least 1 year post tubal ligation) or at least 2 years postmenopausal;
17. Patients with a QTc-prolongation > 470msec, risk factors for torsades de pointes such as heart failure NYHA II-IV, hypokalaemia, family history of long QT syndrome and patients using concomitant medication that prolongs the QT interval.
18. Unwilling or unable to comply with study requirements. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis will include the MITT Population and compare the proportions (%) of Patients achieving a PASI 75 response in the VB-201 20 mg/day group to the placebo group at Week 12 and in the VB-201 80 mg/day group to the placebo group at Week 12. Non-responder imputation (all-cause dropouts and Patients with missing efficacy data at Week 12 are considered non-responders) will be utilized for these MITT population analyses.
These analyses will be performed using the Cochran-Mantel-Haenszel chi-square test. The null hypothesis of equality of PASI 75 response rates will be assessed using a two-sided test at the 5% level of significance
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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) |
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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 | 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 | Yes |
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 | 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 | 9 |
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 | 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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |