Efficacy and Safety of Tildrakizumab in Participants With Moderate-to-Severe Chronic Plaque Psoriasis Who Are Non-Responders to Dimethyl Fumarate Therapy

NCT ID: NCT04263610

Last Updated: 2022-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-04
• Study Completion Date: 2022-02-16

Brief Summary

The purpose of this study is to assess the efficacy, safety and tolerability of Tildrakizumab in moderate-to-severe plaque psoriasis participants who are non-responder to Dimethyl fumarate (DMF) at Week 16. The study consists of two parts. Part 1 will include the first 16 weeks of the Treatment Period and Part 2 will include the last 24 weeks of the Treatment Period.

Conditions

Plaque Psoriasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non-Germany: Dimethyl fumarate standard scheme

Part 1: Participants will receive Dimethyl fumarate (DMF) standard scheme from baseline to Week 16.

Part 2: Participants achieving a Psoriasis Area and Severity Index (PASI) 75 response (responders) and participants failing to achieve a PASI 75 response but having achieved a PASI 50 response (partial responders) at Week 16 will continue with DMF treatment until Week 40. Participants failing to achieve a PASI 50 response (non-responders) at Week 16 will be treated with Tildrakizumab until Week 40.

Group Type: EXPERIMENTAL

Dimethyl fumarate (DMF) standard scheme

Intervention Type: DRUG

Participants will receive DMF gastro-resistant tablet orally from baseline to Week 16, at a dose of 30 milligrams (mg) once daily, twice daily, thrice daily in Week 1, Week 2, Week 3 respectively, 120 mg only once in Week 4. Participants will increase DMF dose by 120 mg tablet per week for the subsequent 5 weeks. Participants achieving Psoriasis area and severity Index (PASI) 50-75 (partial responder) or 75 (responder) will continue the DMF treatment until Week 40. The maximum daily dose taken by a participant will be 720 mg.

Tildrakizumab

Intervention Type: DRUG

Participants who achieve PASI less than (\<) 50 (non-responders) at Week 16 will receive Tildrakizumab subcutaneous injection at a dose of either 100 or 200 mg \[(as per the Summary of Product Characteristics (SmPC)\] at Weeks 16, 20 and 32 up to Week 40.

Germany: Dimethyl fumarate standard scheme

Part 1: Participants will receive DMF standard scheme from Baseline to Week 16. Part 2: Participants achieving a PASI 75 response (responders) and participants failing to achieve a PASI 75 response but having achieved a PASI 50 response (partial responders) at Week 16 will continue with DMF treatment until Week 40. Participants failing to achieve a PASI 50 response (non-responders) at Week 16 will be treated with Tildrakizumab until Week 40.

Group Type: EXPERIMENTAL

Dimethyl fumarate (DMF) standard scheme

Intervention Type: DRUG

Participants will receive DMF gastro-resistant tablet orally from baseline to Week 16, at a dose of 30 milligrams (mg) once daily, twice daily, thrice daily in Week 1, Week 2, Week 3 respectively, 120 mg only once in Week 4. Participants will increase DMF dose by 120 mg tablet per week for the subsequent 5 weeks. Participants achieving Psoriasis area and severity Index (PASI) 50-75 (partial responder) or 75 (responder) will continue the DMF treatment until Week 40. The maximum daily dose taken by a participant will be 720 mg.

Tildrakizumab

Intervention Type: DRUG

Participants who achieve PASI less than (\<) 50 (non-responders) at Week 16 will receive Tildrakizumab subcutaneous injection at a dose of either 100 or 200 mg \[(as per the Summary of Product Characteristics (SmPC)\] at Weeks 16, 20 and 32 up to Week 40.

Germany: Dimethyl fumarate simplified scheme

Part 1: Participants will receive DMF simplified scheme from Baseline to Week 16.

Part 2: Participants achieving a PASI 75 response (responders) and participants failing to achieve a PASI 75 response but having achieved a PASI 50 response (partial responders) at Week 16 will continue with DMF treatment until Week 40. Participants failing to achieve a PASI 50 response (non-responders) at Week 16 will be treated with Tildrakizumab until Week 40.

Group Type: EXPERIMENTAL

Dimethyl fumarate (DMF) simplified scheme

Intervention Type: DRUG

Participants will receive DMF gastro-resistant tablet orally at a dose of 60, 120, 180, 240, 360 mg daily in Week 1, Week 2, Week 3, Week 4, Week 5 respectively, and 480 mg daily from Week 6 to Week 8. If a PASI is greater than or equal to (\>=) 30% at Week 8, no dose increase will be done and if PASI is less than (\<) 30% at Week 8, participants will receive 600 mg daily in Week 9 and 720 mg from the Week 10 onwards.

Tildrakizumab

Intervention Type: DRUG

Participants who achieve PASI less than (\<) 50 (non-responders) at Week 16 will receive Tildrakizumab subcutaneous injection at a dose of either 100 or 200 mg \[(as per the Summary of Product Characteristics (SmPC)\] at Weeks 16, 20 and 32 up to Week 40.

Interventions

Dimethyl fumarate (DMF) standard scheme

Participants will receive DMF gastro-resistant tablet orally from baseline to Week 16, at a dose of 30 milligrams (mg) once daily, twice daily, thrice daily in Week 1, Week 2, Week 3 respectively, 120 mg only once in Week 4. Participants will increase DMF dose by 120 mg tablet per week for the subsequent 5 weeks. Participants achieving Psoriasis area and severity Index (PASI) 50-75 (partial responder) or 75 (responder) will continue the DMF treatment until Week 40. The maximum daily dose taken by a participant will be 720 mg.

Intervention Type: DRUG

Dimethyl fumarate (DMF) simplified scheme

Participants will receive DMF gastro-resistant tablet orally at a dose of 60, 120, 180, 240, 360 mg daily in Week 1, Week 2, Week 3, Week 4, Week 5 respectively, and 480 mg daily from Week 6 to Week 8. If a PASI is greater than or equal to (\>=) 30% at Week 8, no dose increase will be done and if PASI is less than (\<) 30% at Week 8, participants will receive 600 mg daily in Week 9 and 720 mg from the Week 10 onwards.

Intervention Type: DRUG

Tildrakizumab

Participants who achieve PASI less than (\<) 50 (non-responders) at Week 16 will receive Tildrakizumab subcutaneous injection at a dose of either 100 or 200 mg \[(as per the Summary of Product Characteristics (SmPC)\] at Weeks 16, 20 and 32 up to Week 40.

Intervention Type: DRUG

Other Intervention Names

Skilarence®; Skilarence®; Ilumetri®

Eligibility Criteria

Inclusion Criteria

• Provide signed written and dated informed consent given before any study related activity is performed
• Participants with at least 6 months history of chronic plaque psoriasis
• Participants diagnosed with moderate-to-severe plaque psoriasis at the Screening Visit
• Candidate for systemic treatment for plaque psoriasis at the Screening Visit

Exclusion Criteria

• Women currently pregnant, or intend to become pregnant or breastfeeding. Unwillingness/inability for the participants (women or men) to use appropriate measures of contraception (if necessary)
• Other forms of psoriasis than chronic plaque-type
• Participants with drug-induced psoriasis at the Screening Visit
• Participants with history or evidence of skin disease or conditions other than chronic plaque-type psoriasis
• Participants with history of hypersensitivity or allergy to the study drugs
• Concurrent malignancy, current relevant autoimmune diseases other than psoriasis
• Participants with severe renal impairment, haematological abnormality and abnormal liver enzymes at the Screening visit
• Active infectious disease at the Screening Visit
• Participants positive test for human immunodeficiency virus or any other immunosuppressive disease
• Previous exposure to fumarate-based drug or a biologic systemic treatment
• Live vaccination within 4 weeks prior to the Baseline Visit
• Participant who intend to use any concomitant medication with immunomodulating or systemic corticosteroids
• Unable to comply with the requirements of the study or who in the opinion of the study physician should not participate in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Almirall, S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Almirall, SAS

Locations

Investigator Site 3

Augsburg, , Germany

Investigator Site 1

Bristol, , United Kingdom

Investigator Site 2

London, , United Kingdom

Countries

Germany; United Kingdom

Other Identifiers

2019-000817-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M-14745-41

Identifier Type: -

Identifier Source: org_study_id