An open-label, randomized, Phase IV study, to assess the efficacy and safety of tildrakizumab in patients with moderate to severe chronic plaque psoriasis who are non-responders to dimethyl fumarate therapy

Phase 1

• Conditions: Moderate to severe chronic plaque psoriasis; MedDRA version: 20.0 Level: LLT Classification code 10071117 Term: Plaque psoriasis System Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2019-000817-35-GB
• Lead Sponsor: Almirall

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-30
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 250

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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 glucosegalactose 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 o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified