Clinical trial NCT03331835: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psoriasis Vulgaris
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Having Least 75% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 75 Response) From Baseline at Week 24
timeFrame: Baseline to Week 24
measure: Static Physician's Global Assessment (sPGA) Scale Score of 0 or 1 at Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Having Least 90% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 90 Response) From Baseline at Week 24
timeFrame: Baseline to Week 24
measure: Having 100% Lower Psoriasis Area and Severity Index (PASI) Score Relative to Baseline (PASI 100 Response) From Baseline at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in PASI Score
timeFrame: Baseline to Week 24
measure: Percent Change From Baseline in PASI Score at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Affected Body Surface Area (BSA)
timeFrame: Baseline to Week 24
measure: Psoriasis Symptom Inventory (PSI) Responder at Week 24 (Total Score ≤ 8, With no Item Scores > 1)
timeFrame: Week 24
measure: PSI Total Score of 0 at Week 24
timeFrame: Week 24
measure: Number of Symptom-free Days From Randomisation to Week 24
timeFrame: Baseline to Week 24
measure: Burden of Symptoms
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in Dermatology Life Quality Index (DLQI) Total Score
timeFrame: Baseline to Week 24
measure: DLQI Total Score of 0 or 1 at Week 24
timeFrame: Week 24
Other outcomes:
measure: Change From Baseline at Week 24 in NAPSI Total Score
timeFrame: Baseline to Week 24
Locations:
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim Klinik für Dermatologie
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie Psoriasis Studien Zentrum
city: Berlin
country: Germany
facility: Rothhaar Studien GmbH Dermatologisches Studienzentrum
city: Berlin
country: Germany
facility: Hautarztpraxis Dr. Wildfeuer
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld Klinik für Dermatologie und Allergologie
city: Bochum
country: Germany
facility: Hauttumorzentrum Ruhr- Universität im St. Josef Hospital
city: Bochum
country: Germany
facility: Hautarztpraxis Dr. Niesmann und Dr. Othlinghaus
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn (AöR) Klinik und Poliklinik für Dermatologie und Allergologie
city: Buxtehude
country: Germany
facility: Elbe Klinikum Buxtehude Klinik für Dermatologie
city: Darmstadt
country: Germany
facility: Rosenpark Research
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Klinik und Poliklinik für Dermatologie
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen Hautklinik
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Klinik für Dermatologie
city: Friedrichshafen
country: Germany
facility: Derma-Study-Center-Friedrichshafen
city: Gelsenkirchen
country: Germany
facility: Gemeinschaftspraxis Rotterdam & Kollegen Facharzt für Haut & Geschlechtskrankheiten
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen
city: Hamburg
country: Germany
facility: SCIderm GmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover Klinik für Dermatologie Allergologie und Venerologie
city: Heidelberg
country: Germany
facility: Universitäts-Hautklinik Heidelberg
city: Kiel
country: Germany
facility: Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Schleswig-Holstein, Campus Kiel Psoriasis-Zentrum
city: Lübeck
country: Germany
facility: Exellenzzentrum Entzündungsmedizin (CCIM) Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Mainz
country: Germany
facility: University Medical Center Mainz Department of Dermatology and Allergy, Clinical Research Center
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim der Universität Heidelberg Klinik für Dermatologie, Venerologie und Allergologie
city: München
country: Germany
facility: Technische Universität München Klinik und Poliklinik für Dermatologie und Allergologie
city: Osnabrück
country: Germany
facility: Klinische Forschung Osnabrück - Klifos
city: Recklinghausen
country: Germany
facility: KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen Klinik für Dermatologie und Allergologie
city: Schweinfurt
country: Germany
facility: Gemeinschaftspraxis Weber & Crainic
city: Stuttgart
country: Germany
facility: Hautarztpraxis Dres. Leitz
city: Tübingen
country: Germany
facility: University Medical Center University of Tübingen
city: Witten
country: Germany
facility: Hautarztpraxis
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References: