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

NCT04263610 | Completed Phase 4

• 2 other identifiers: M-14745-412019-000817-35
• Study Type: interventional
• Target: 190
• Locations: 2 countries
• Sites: 3

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

Keywords

Dimethyl fumarate; Tildrakizumab; Moderate-to-severe plaque psoriasis; Chronic Plaque Psoriasis

Outcome Measures

Primary Outcomes (1)

• Part 2: Percentage of Participants Achieving a Psoriasis Area Severity Index 75 (PASI 75) after Tildrakizumab Treatment at Week 40

  PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and scaling on a scale range from 0 (no symptoms) to 4 (very marked), together with the percentage (%) of the area affected, rated on a scale from 0 (0%) to 6 (90-100%). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 (no psoriasis) to 72 (the most severe disease). PASI 75 response, is defined as having an improvement (reduction) of greater than or equal to (\>=) 75% in PASI score compared to the baseline score.

  Week 40

Secondary Outcomes (36)

• Part 1 and Part 2: Percentage of Participants Achieving PASI 50, PASI 75, PASI 90 and PASI 100 (Only for Part 2) Responses

  Part 1: Weeks 8 and 16; Part 2: DMF: Weeks 24, 36 and 40, Tildrakizumab: Weeks 20, 32 and 40

• Part 1 and Part 2: Percentage of Participants Achieving an Absolute Psoriasis Area and Severity Index (PASI) Score Less Than or Equal to (<=) 5, 3 and 1

  Part 1: Weeks 8 and 16; Part 2: DMF: Weeks 24, 36 and 40, Tildrakizumab: Weeks 20, 32 and 40

• Part 1 and Part 2: Absolute Psoriasis Area Severity Index (PASI) Score

  Part 1: Weeks 8 and 16; Part 2: DMF: Weeks 24, 36 and 40, Tildrakizumab: Weeks 20, 32 and 40

• Part 1 and Part 2: Change from Baseline in Absolute Psoriasis Area and Severity Index (PASI) Score

  Part 1: Baseline, Weeks 8 and 16; Part 2: DMF: Baseline, Weeks 24, 36 and 40, Tildrakizumab: Baseline, Weeks 20, 32 and 40

• Part 1 and Part 2: Absolute Body Surface Area (BSA) Score

  Part 1: Weeks 8 and 16; Part 2: DMF: Weeks 24, 36 and 40, Tildrakizumab: Weeks 20, 32 and 40

Study Arms (3)

Non-Germany: Dimethyl fumarate standard scheme

EXPERIMENTAL

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.

Drug: Dimethyl fumarate (DMF) standard scheme; Drug: Tildrakizumab

Germany: Dimethyl fumarate standard scheme

EXPERIMENTAL

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.

Drug: Dimethyl fumarate (DMF) standard scheme; Drug: Tildrakizumab

Germany: Dimethyl fumarate simplified scheme

EXPERIMENTAL

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.

Drug: Dimethyl fumarate (DMF) simplified scheme; Drug: Tildrakizumab

Interventions

Dimethyl fumarate (DMF) standard scheme 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.

Also known as: Skilarence®

Germany: Dimethyl fumarate standard scheme; Non-Germany: Dimethyl fumarate standard scheme

Dimethyl fumarate (DMF) simplified scheme 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.

Also known as: Skilarence®

Germany: Dimethyl fumarate simplified scheme

Tildrakizumab 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.

Also known as: Ilumetri®

Germany: Dimethyl fumarate simplified scheme; Germany: Dimethyl fumarate standard scheme; Non-Germany: Dimethyl fumarate standard scheme

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Almirall, S.A.: lead

Study Sites (3)

Investigator Site 3

Augsburg, Germany

Location

Investigator Site 1

Bristol, United Kingdom

Location

Investigator Site 2

London, United Kingdom

Location

MeSH Terms

Interventions

Dimethyl Fumarate; tildrakizumab

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Study Director

  Almirall, SAS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2020
• First Posted: February 11, 2020
• Study Start: September 4, 2019
• Primary Completion: February 16, 2022
• Study Completion: February 16, 2022
• Last Updated: May 27, 2022

Record last verified: 2022-05

Locations

DE (1); GB (2)