| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe chronic plaque psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Moderate to severe chronic 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 | 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 assess the efficacy of tildrakizumab treatment (as assessed by PASI 75) in moderate-to-severe plaque psoriasis patients who are non-responders to DMF |
|
| E.2.2 | Secondary objectives of the trial |
- assess the efficacy of tildrakizumab treatment in moderate-to-severe plaque psoriasis patients who are non-responders to DMF:
- PASI, BSA, PGA, scalp PGA, palmoplantar PGA
- DLQI, Skindex-16, pruritus-VAS, MOSS
- assess the safety, tolerability of tildrakizumab treatment in moderate-to-severe plaque psoriasis patients who are non-responders to DMF
- assess the efficacy of DMF treatment in moderate-to-severe plaque psoriasis patients:
- PASI, BSA, PGA, scalp PGA, palmoplantar PGA
- DLQI, Skindex-16, pruritus-VAS, MOSS
- explore patient’s adherence rate to DMF treatment in moderate-to-severe plaque psoriasis patients
- assess the safety, tolerability of DMF treatment in moderate-to-severe plaque psoriasis patients
Exploratory objectives (part 1, Germany subgroup)
Compare efficacy, safety, tolerability, adherence rate between standard and simplified DMF dosing schemes after 16 w of treatment in moderate-to-severe plaque psoriasis patients |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Ability to understand and comply with the requirements of the study and communicate with the Investigator, and written, signed and dated informed consent given before any study related activity is performed.
2. Male or female, aged 18 years at the time of the Screening Visit.
3. Diagnosed with chronic plaque psoriasis of at least 6 months prior to the Screening Visit, and has stable active plaque-type psoriasis (stable is defined as without clinically significant flares during the 12 weeks before the Baseline Visit).
4. Moderate-to-severe plaque psoriasis at the Screening and Baseline visits as defined by PASI score of ≥ 10
5. Complete record of at least the last 12 months prior to the Screening Visit of anti-psoriatic previous topical, phototherapy and non-biologic systemic treatments, if any.
6. Candidate for systemic treatment for plaque psoriasis at the Screening Visit
7. General good health, or a stable medical condition not considered likely to interfere with the conduct of the clinical study, as determined by the Investigator based upon results of medical history, laboratory results (within normal or clinically acceptable range limits) and physical examination (no clinical significant abnormal findings). Investigators are encouraged to consult with the Sponsor if there are questions regarding the significance of any out of range values.
8. Unlikely to conceive, as indicated by at least one “yes” answer to the following questions:
a. Patient is a male.
b. Patient is a surgically sterilized female by hysterectomy or bilateral tubal ligation.
c. Patient is a postmenopausal female ≥45 years of age with >1 year since last menses. If a patient is <45 years of age, or cessation of menses is more than 3 months and less than 1 year, follicle stimulating hormone must be documented as elevated into the postmenopausal range (>60 mIU/mL) at the Screening visit.
d. Patient is a non-sterilized and pre-menopausal female using a highly effective medically accepted method of contraception, during the study period and for 4 or 17 weeks after the last dose of DMF or tildrakizumab, respectively.
9. For female patients of child-bearing potential, a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Additionally, they must agree to have urine pregnancy tests while on study medication. |
|
| E.4 | Principal exclusion criteria |
1. Female patients who are currently pregnant, who intend to become pregnant during the course of the study, or who are breastfeeding. Also if there is unwillingness/inability for the patients (women or men) to use appropriate measures of contraception (if necessary).
2. Current forms of psoriasis other than chronic plaque-type (e.g. erythrodermic, guttate, or pustular psoriasis)
3. Drug-induced psoriasis (i.e., a new onset or current exacerbation of psoriasis from beta-blockers, calcium channel blockers, or lithium) at the Screening Visit
4. History or evidence of skin disease (atopic dermatitis, eczema) or conditions (scarring, open wounds) other than chronic plaque-type psoriasis that might interfere with the study conduct or evaluations, or which exposes the patient to unacceptable risk by study participation
5. History of hypersensitivity or allergy to the study drugs or its excipients, which include lactose*
*People with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not be included in the study.
6. History of 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).
7. History of or current relevant autoimmune diseases (e.g. lupus-like syndromes) other than psoriasis.
8. Active significant gastrointestinal problems (ulcers, diarrhoea, etc.) at the Screening Visit
9. Severe renal impairment (creatinine clearance <30 mL/min, estimated glomerular filtration rate [eGFR] using CKD-EPI Creatinine Equation) or significant proteinuria (3+ or higher measured by dipstick) at the Screening Visit.
10. Any of the following haematological abnormality at the Screening Visit:
a. Platelet count < 100,000/mm3
b. White blood cell count < 3,000 cells/mm3,
c. Lymphocyte count <1.000/μl,
d. Haemoglobin, haematocrit, or red blood cell count outside 30 % of the upper or lower limits of normal for the laboratory
11. Abnormal liver enzymes at the Screening Visit:
a. If an enzyme was >3x the upper limit of the normal range (ULN): aspartate amino transferase (AST; serum glutamic oxaloacetic transaminase [SGOT]), alanine amino transferase (ALT; serum glutamic pyruvic transaminase [SGPT]), gamma-glutamyl-transferase (GGT), alkaline phosphatase (ALP)
b. If bilirubin was >2x ULN, for the other liver enzymes >2x ULN was exclusionary
12. Active infectious disease at the Screening Visit
13. Known positive test for human immunodeficiency virus or any other immunosuppressive disease
14. Known latent or active tuberculosis (TB) at the Screening visit
15. History (within 2 years prior to the Screening Visit) or evidence/indication of current drug and/or alcohol abuse or dependence, according to the judgment of the Investigator
16. Previous exposure to fumarate-based drug or a biologic systemic treatment (e.g. tumour necrosis factor-alpha inhibitors, IL-17 inhibitors, IL-17R inhibitors, IL-12/23 p40 inhibitors, IL-23p19 inhibitors or experimental biological product)
17. Have had a live vaccination within 4 weeks prior to the Baseline Visit, or intend to have a live vaccination during the course of the study, or have participated in a vaccine clinical study within 12 weeks of the Baseline Visit
18. Patient who intend to use any concomitant medication not permitted by this study or who have not undergone the required washout period, prior to the Baseline Visit, for a particular prohibited medication:
a. Topical psoriasis treatment (e.g. topical corticosteroids, vitamin A analogues, vitamin D analogues, coal tar, anthracene derivatives, salicylic acid preparations): 2 weeks
b. Phototherapy (e.g. UV-B light phototherapy, Psoralen-UVA therapy, tanning salon or home-administered UVB): 4 weeks
c. Conventional systemic anti-psoriatic drugs (e.g. cyclosporine, methotrexate, apremilast or acitretin) excluding fumarate-based drugs: 4 weeks
d. Any other immunosuppressive medication (e.g. cytostatics, etc.): 6 months
19. Concomitant treatment with immunomodulating or systemic corticosteroid.
20. Participating in a drug investigational trial within the 30 days (or five half-lives, whichever is longer) prior to enrolment.
21. Concurrent systemic therapy with drugs that may interfere with the study drugs taken within the defined washout period
22. Previously included in the current study
23. Patient who is employee at the research site or Almirall
24. Patient with any other serious or uncontrolled physical or mental dysfunction that, as judged by the Investigator, could place the patient at higher risk derived from his/her participation in the study, could confound the results of the study or is likely to prevent the patient from complying with the requirements of the study or completing the study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Endpoint (Part 2)
Proportion of patients who were non-responders to DMF at Week 16 that were treated with Tildrakizumab and achieved a PASI 75 at week 40. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints (Part 1 and Part 2):
Efficacy endpoints (Part 1)
- Proportion of patients achieving PASI 50, PASI 75 and PASI 90 responses at Week 8 and Week 16 Visits of the Part 1
- Proportion of patients achieving absolute PASI scores of ≤5, ≤3 and ≤1 at Week 8 and Week 16 Visits of the Part 1
- Absolute PASI score and change in the absolute PASI score at Week 8 and Week 16 Visits of the Part 1
- Absolute BSA score and change from baseline in the absolute BSA score at Week 8 and Week 16 Visits of the Part 1
- Proportion of patients achieving PGA, ScPGA† and PPPGA‡ scores of 0 or 1 at Week 8 and Week 16 Visits of the Part 1
- Absolute PGA, ScPGA† and PPPGA‡ scores and change in the absolute PGA, ScPGA† and PPPGA‡ scores at Week 8 and Week 16 Visits of the Part 1
- Proportion of patients achieving DLQI scores of 0 or 1 at Week 8 and Week 16 Visits of the Part 1
- Absolute DLQI score and change from baseline in the absolute DLQI score at Week 8 and Week 16 Visits of the Part 1
- Absolute Skindex-16 score and change from baseline in the absolute Skindex-16 score at Week 8 and Week 16 Visits of the Part 1
- Absolute pruritus-VAS score and change from baseline in the absolute pruritus-VAS score at Week 8 and Week 16 Visits of the Part 1
- Absolute MOS score and change from baseline in the absolute MOS score at Week 16 Visit of the Part 1
Efficacy endpoints (Part 2)
- Proportion of patients achieving PASI 50, PASI 75, PASI 90, and PASI 100 responses at each visit of the Part 2.
- Proportion of patients achieving absolute PASI scores of ≤5, ≤3 and ≤1 at each visit of the Part 2
- Absolute PASI score and absolute and percentage change from baseline in the absolute PASI score at each visit of the Part 2
- Absolute BSA score and change from baseline in the absolute BSA score at each visit of the Part 2
- Proportion of patients achieving PGA, ScPGA† and PPPGA‡ scores of 0 or 1 at each visit of the Part 2
- Absolute PGA, ScPGA† and PPPGA‡ scores and absolute and percentage change from baseline in the absolute PGA, ScPGA† and PPPGA‡ scores at each visit of the Part 2Proportion of patients achieving DLQI score of 0 or 1 at Week 32 and Week 40 Visits of the Part 2
- Absolute DLQI score and absolute and percentage change from baseline in the absolute DLQI score at Week 32 and Week 40 Visits of the Part 2
- Absolute Skindex-16 score and absolute and percentage change from baseline in the absolute Skindex-16 score at Week 32 and Week 40 Visits of the Part 2
- Absolute pruritus-VAS score and absolute and percentage change from baseline in the absolute pruritus-VAS score at each visit of the Part 2
- Absolute MOS score and absolute and percentage change from baseline in the absolute MOS score at Week 40 Visit of the Part 2
† Only in patients with scalp involvement
‡ Only in patients with palmar or plantar involvement
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 28 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 | 6 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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