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

LEO Pharma210 enrolled

Overview

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.

A 24-week, randomised, open-label, active-controlled, parallel group, multi-centre trial with investigator-blinded efficacy assessments

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

210

Conditions

Psoriasis Vulgaris

Interventions

BrodalumabBIOLOGICAL

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.

Fumaric acid estersDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Main Criteria for Inclusion: * 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. Main Criteria for Exclusion: * 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: 1. Have received phototherapy (UVA light therapy without psoralens, UVB light therapy, excimer laser, tanning beds etc. within 4 weeks of baseline, or 2. Have had topical psoriasis treatment within 2 weeks of baseline (exceptions: bland emollients without urea or beta or alpha hydroxy acids) 3. 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 4. 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: 1. Leukocyte cell count below 3×10\^9/L or lymphocyte count below 0.7×10\^9/L 2. Aspartate aminotransferase (AST) or alanine transferase (ALT) \> 2× ULN (upper level of normal limit) 3. Absolute neutrophil count \< 2×10\^9/L 4. 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. * A PHQ-8 score of ≥10 corresponding to moderate to severe depression at screening.

Locations (30)

Outcomes

Primary Outcomes

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).

Time frame: 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).

Time frame: Baseline to Week 24

Secondary Outcomes

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

Time frame: 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

Data from ClinicalTrials.gov

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Fachklinik Bad Bentheim Klinik für Dermatologie

Bad Bentheim, Germany

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

Berlin, Germany

Rothhaar Studien GmbH Dermatologisches Studienzentrum

Berlin, Germany

Hautarztpraxis Dr. Wildfeuer

Berlin, Germany

Klinikum Bielefeld Klinik für Dermatologie und Allergologie

Bielefeld, Germany

Hauttumorzentrum Ruhr- Universität im St. Josef Hospital

Bochum, Germany

Hautarztpraxis Dr. Niesmann und Dr. Othlinghaus

Bochum, Germany

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

Bonn, Germany

Elbe Klinikum Buxtehude Klinik für Dermatologie

Buxtehude, Germany

Rosenpark Research

Darmstadt, Germany

...and 20 more locations

Time frame: Baseline to Week 24

Change From Baseline at Week 24 in PASI Score

Time frame: Baseline to Week 24

Percent Change From Baseline in PASI Score at Week 24

Time frame: Baseline to Week 24

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

The surface area of the participant's hand (palm and fingers) is used as a reference measurement to calculate the percentage of each body region that is affected by psoriasis. One hand is approximately equal to 1% total BSA. Furthermore, the complete body surface area (BSA=100%) can be divided into regions that approximates percentages of BSA as follows: head and neck (10%), upper extremities (20%), the trunk including the axillae and groin (30%), and finally the lower extremities, including the buttocks (40%). A negative value in the percent change from baseline that the affected BSA was lower at the time of data collection.

Time frame: Baseline to Week 24

Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1)

The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms. PSI response is defined as total score ≤8 and no item score \>1. Symptom-free day is defined as having daily total PSI of 0 on that day.

Time frame: Week 24

PSI Total Score of 0 at Week 24

Time frame: Week 24

Number of Symptom-free Days From Randomisation to Week 24

Time frame: Baseline to Week 24

Burden of Symptoms

Burden of symptoms was assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment. The AUC for the PSI total score was calculated for each participant using the standard trapezoidal rule. The AUC was normalised by dividing it with the time from baseline to the last available assessment of the PSI total score. The PSI consists of eight psoriasis-specific questions. Trial participants rated the severity of their symptoms in the last 24 hours from 'not at all' to 'very severe,' ranging from 0 to 4. Total scores range from 0 to 32 with higher scores indicating worse symptoms.

Time frame: Baseline to Week 24

Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score

DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

Time frame: Baseline to Week 24

DLQI Total Score of 0 or 1 at Week 24

DLQI consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.

Time frame: Week 24