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

Psoriasis Vulgaris Clinical Trial

Official title:

A Phase 4 Trial Comparing the Efficacy of Subcutaneous Injections of Brodalumab to Oral Administrations of Fumaric Acid Esters in Adults With Moderate to Severe Plaque Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03331835
• Other study ID #: LP0160-1327
• Secondary ID: 2016-003867-21
• Status: Completed
• Phase: Phase 4
• Start date: November 3, 2017
• Est. completion date: March 21, 2019

Study information

• Verified date: February 2020
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.>

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: March 21, 2019
• Est. primary completion date: January 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.>

Related Conditions & MeSH terms

• Psoriasis
• Psoriasis Vulgaris

Intervention

Biological:
• Brodalumab
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.

Drug:
• Fumaric acid esters
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.

Locations

Country	Name	City	State
Germany	Fachklinik Bad Bentheim Klinik für Dermatologie	Bad Bentheim
Germany	Charité - Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie Psoriasis Studien Zentrum	Berlin
Germany	Hautarztpraxis Dr. Wildfeuer	Berlin
Germany	Rothhaar Studien GmbH Dermatologisches Studienzentrum	Berlin
Germany	Klinikum Bielefeld Klinik für Dermatologie und Allergologie	Bielefeld
Germany	Hautarztpraxis Dr. Niesmann und Dr. Othlinghaus	Bochum
Germany	Hauttumorzentrum Ruhr- Universität im St. Josef Hospital	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	Universitätsklinikum Carl Gustav Carus Klinik und Poliklinik für Dermatologie	Dresden
Germany	Universitätsklinikum Erlangen Hautklinik	Erlangen
Germany	Universitätsklinikum Frankfurt Klinik für Dermatologie	Frankfurt
Germany	Derma-Study-Center-Friedrichshafen	Friedrichshafen
Germany	Gemeinschaftspraxis Rotterdam & Kollegen Facharzt für Haut & Geschlechtskrankheiten	Gelsenkirchen
Germany	SCIderm GmbH	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen	Hamburg
Germany	Medizinische Hochschule Hannover Klinik für Dermatologie Allergologie und Venerologie	Hannover
Germany	Universitäts-Hautklinik Heidelberg	Heidelberg
Germany	Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Schleswig-Holstein, Campus Kiel Psoriasis-Zentrum	Kiel
Germany	Exellenzzentrum Entzündungsmedizin (CCIM) Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	University Medical Center Mainz Department of Dermatology and Allergy, Clinical Research Center	Mainz
Germany	Universitätsklinikum Mannheim der Universität Heidelberg Klinik für Dermatologie, Venerologie und Allergologie	Mannheim
Germany	Technische Universität München Klinik und Poliklinik für Dermatologie und Allergologie	München
Germany	Klinische Forschung Osnabrück - Klifos	Osnabrück
Germany	KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen Klinik für Dermatologie und Allergologie	Recklinghausen
Germany	Gemeinschaftspraxis Weber & Crainic	Schweinfurt
Germany	Hautarztpraxis Dres. Leitz	Stuttgart
Germany	University Medical Center University of Tübingen	Tübingen
Germany	Hautarztpraxis	Witten

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline at Week 24 in NAPSI Total Score	The Nail Psoriasis Severity Index (NAPSI) grades nails by first dividing the nail area with imaginary horizontal and vertical lines into 4 quarters. The following 8 clinical features of nail psoriasis are then scored based on the number of quarters in which the feature is present (0 to 4) to arrive at a NAPSI score of 0 to 32 for each nail: Pitting.; Leukonychia.; Red spots in lunula.; Nail plate crumbling.; Oil drop (salmon patch) discoloration.; Onycholysis.; Nail bed hyperkeratosis.; Splinter haemorrhages.; A negative change in NAPSI score means that the NAPSI score was lower at the time of data collection.	Baseline to Week 24
Primary	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
Primary	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	Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 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
Secondary	Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 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
Secondary	Change From Baseline at Week 24 in PASI Score	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).; A negative change in PASI score means that the PASI score was lower at the time of data collection.	Baseline to Week 24
Secondary	Percent Change From Baseline in PASI Score 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).; A negative value in the percent change from baseline that the PASI score was lower at the time of data collection.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	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.	Week 24
Secondary	PSI Total Score of 0 at Week 24	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.	Week 24
Secondary	Number of Symptom-free Days From Randomisation to Week 24	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.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	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.	Baseline to Week 24
Secondary	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.	Week 24