A Trial Comparing the Efficacy of Subcutaneous Injections of Brodalumab to Oral Administrations of Fumaric Acid Esters in Adults With Moderate to Severe Plaque Psoriasis

NCT03331835 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: LP0160-13272016-003867-21
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 30

Brief Summary

The primary objective is to demonstrate added benefit of brodalumab versus a selected systemic comparator in treatment of moderate to severe plaque psoriasis in Germany in subjects who have not previously received systemic treatment for psoriasis. Fumaric acid esters have been selected as the comparator because it is an established systemic treatment of psoriasis in Germany.

Conditions

Psoriasis Vulgaris

Outcome Measures

Primary Outcomes (2)

• Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24

  The PASI score grades the extent and severity of psoriatic involvement for each of four body regions (head and neck, upper extremities, trunk, and lower extremities) using a 7-point scale for extent of involvement in each body region and 5-point scales for severity of each of the clinical signs redness, thickness, and scalliness in each body region. Psoriasis Area and Severity Index is a scale ranging from 0 (no disease) to 72 (maximal disease).

  Baseline to Week 24

• Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24

  sPGA is a 6-point scale that represents the average lesion severity on the trunk and limbs. The assessment is based on the condition of the disease at the time of evaluation. Static Physician's Global Assessment is a scale ranging rom 0 (clear skin) to 5 (severe disease).

  Baseline to Week 24

Secondary Outcomes (11)

• Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24

  Baseline to Week 24

• Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24

  Baseline to Week 24

• Change From Baseline at Week 24 in PASI Score

  Baseline to Week 24

• Percent Change From Baseline in PASI Score at Week 24

  Baseline to Week 24

• Change From Baseline at Week 24 in Affected Body Surface Area (BSA)

  Baseline to Week 24

Other Outcomes (1)

• Change From Baseline at Week 24 in NAPSI Total Score

  Baseline to Week 24

Study Arms (2)

Brodalumab

EXPERIMENTAL

Kyntheum® (brodalumab) pre-filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and hereafter every two weeks (Q2W).

Biological: Brodalumab

Fumaric acid esters

ACTIVE COMPARATOR

Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label.

Drug: Fumaric acid esters

Interventions

Brodalumab BIOLOGICAL

Brodalumab is a recombinant fully human monoclonal immunoglobulin IgG2-antibody that binds with high affinity to human interleukin 17 receptor A (IL-17RA). Blocking IL-17RA inhibits IL-17 cytokine-induced responses and results in reduced or normalised inflammation of the skin in subjects with psoriasis.

Also known as: Kyntheum®

Brodalumab

Fumaric acid esters DRUG

Fumaric acid esters have been used to treat psoriasis since 1959. Systemic therapy with fumaric acid esters is based on an established dosing scheme with a gradual increase to improve tolerability, especially with regards to gastrointestinal side effects.

Also known as: Fumaderm®

Fumaric acid esters

Eligibility Criteria

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

You may qualify if:

• Men or women ≥18 years of age at the time of screening.
• Subjects with chronic plaque type psoriasis diagnosed at least 6 months before randomisation.
• Subjects with moderate to severe plaque psoriasis in whom topical therapy is not adequate and who are candidates for systemic therapy, defined at randomisation by PASI 10, affected BSA \>10%, and DLQI \>10.
• Subject has no known history of active tuberculosis.
• Subject has a negative test for tuberculosis taken at screening (negative Quantiferon test).
• Subject and/or subject's designee is/are capable of administering subcutaneous injections.

You may not qualify if:

• Previous or current systemic treatment of plaque psoriasis or known contraindication for systemic therapy.
• Previous or current PUVA (psoralens and ultraviolet A) therapy.
• Washouts and non-permitted drugs:
• Have received phototherapy (UVA light therapy without psoralens, UVB light therapy, excimer laser, tanning beds etc. within 4 weeks of baseline, or
• Have had topical psoriasis treatment within 2 weeks of baseline (exceptions: bland emollients without urea or beta or alpha hydroxy acids)
• Have received any biologic immune modulating treatments used for indication other than psoriasis within 4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is longer
• Have received any other systemic immune modulating treatment (including but not limited to oral retinoids, methotrexate, calcineurin inhibitors, oral or parenteral corticosteroids etc. used for indications other than psoriasis) within 4 weeks of baseline or within a period of 5 half-lives of the IMP, whichever is longer.
• Subjects with any of the following laboratory abnormalities at screening:
• Leukocyte cell count below 3×10\^9/L or lymphocyte count below 0.7×10\^9/L
• Aspartate aminotransferase (AST) or alanine transferase (ALT) \> 2× ULN (upper level of normal limit)
• Absolute neutrophil count \< 2×10\^9/L
• Serum creatinine \> ULN.
• History of depressive disorder within the last 2 years including current antidepressive treatment.
• Subjects with a history of suicidal behaviour (suicide attempt).
• Any suicidal ideation of severity 4 or 5 based on the eC-SSRS questionnaire at screening.

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (30)

Fachklinik Bad Bentheim Klinik für Dermatologie

Bad Bentheim, 48455, Germany

Location

Charité - Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie Psoriasis Studien Zentrum

Berlin, 10117, Germany

Location

Rothhaar Studien GmbH Dermatologisches Studienzentrum

Berlin, 10783, Germany

Location

Hautarztpraxis Dr. Wildfeuer

Berlin, 13055, Germany

Location

Klinikum Bielefeld Klinik für Dermatologie und Allergologie

Bielefeld, 33647, Germany

Location

Hauttumorzentrum Ruhr- Universität im St. Josef Hospital

Bochum, 44791, Germany

Location

Hautarztpraxis Dr. Niesmann und Dr. Othlinghaus

Bochum, 44793, Germany

Location

Universitätsklinikum Bonn (AöR) Klinik und Poliklinik für Dermatologie und Allergologie

Bonn, 53127, Germany

Location

Elbe Klinikum Buxtehude Klinik für Dermatologie

Buxtehude, 21614, Germany

Location

Rosenpark Research

Darmstadt, 64283, Germany

Location

Universitätsklinikum Carl Gustav Carus Klinik und Poliklinik für Dermatologie

Dresden, 01307, Germany

Location

Universitätsklinikum Erlangen Hautklinik

Erlangen, 91054, Germany

Location

Universitätsklinikum Frankfurt Klinik für Dermatologie

Frankfurt, 60590, Germany

Location

Derma-Study-Center-Friedrichshafen

Friedrichshafen, 88045, Germany

Location

Gemeinschaftspraxis Rotterdam & Kollegen Facharzt für Haut & Geschlechtskrankheiten

Gelsenkirchen, 45883, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen

Hamburg, 20246, Germany

Location

SCIderm GmbH

Hamburg, 20354, Germany

Location

Medizinische Hochschule Hannover Klinik für Dermatologie Allergologie und Venerologie

Hanover, 30625, Germany

Location

Universitäts-Hautklinik Heidelberg

Heidelberg, 69120, Germany

Location

Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Schleswig-Holstein, Campus Kiel Psoriasis-Zentrum

Kiel, 24105, Germany

Location

Exellenzzentrum Entzündungsmedizin (CCIM) Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, 23538, Germany

Location

University Medical Center Mainz Department of Dermatology and Allergy, Clinical Research Center

Mainz, 55131, Germany

Location

Universitätsklinikum Mannheim der Universität Heidelberg Klinik für Dermatologie, Venerologie und Allergologie

Mannheim, 68167, Germany

Location

Technische Universität München Klinik und Poliklinik für Dermatologie und Allergologie

München, 80802, Germany

Location

Klinische Forschung Osnabrück - Klifos

Osnabrück, 49074, Germany

Location

KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen Klinik für Dermatologie und Allergologie

Recklinghausen, 45657, Germany

Location

Gemeinschaftspraxis Weber & Crainic

Schweinfurt, 97421, Germany

Location

Hautarztpraxis Dres. Leitz

Stuttgart, 70178, Germany

Location

University Medical Center University of Tübingen

Tübingen, 72076, Germany

Location

Hautarztpraxis

Witten, 58453, Germany

Location

MeSH Terms

Interventions

brodalumab; Fumarates; Dimethyl Fumarate

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Operational challenges with the ePRO diary device given to trial participants led to missing data at baseline and Week 24. This made the analyses of the secondary patient-reported endpoints PSI response rate and PSI total score of 0 or 1 impossible.

Results Point of Contact

• Title: Clinical Disclosure
• Organization: LEO Pharma AS

disclosure@leo-pharma.com

(+1) 877-557-1168

Study Officials

• Medical Expert

  LEO Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2017
• First Posted: November 6, 2017
• Study Start: November 3, 2017
• Primary Completion: January 24, 2019
• Study Completion: March 21, 2019
• Last Updated: March 13, 2025
• Results First Posted: February 10, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (30)