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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

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ClinicalTrials.gov Identifier: NCT03331835
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
LEO Pharma

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.


Condition or disease Intervention/treatment Phase
Psoriasis Vulgaris Biological: Brodalumab Drug: Fumaric acid esters Phase 4

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 3, 2017
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: Brodalumab
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

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.

Other Name: Kyntheum®

Active Comparator: Fumaric acid esters

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
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.
Other Name: Fumaderm®




Primary Outcome Measures :
  1. At least 75% improvement from baseline at Week 24 in Psoriasis Area and Severity Index (PASI) [ Time Frame: baseline to 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.

  2. Static Physician's Global Assessment (sPGA) scale score of 0 or 1 at Week 24 [ Time Frame: 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.


Secondary Outcome Measures :
  1. At least 90% improvement from baseline at Week 24 in PASI [ Time Frame: baseline to Week 24 ]
  2. 100% improvement from baseline at Week 24 in PASI [ Time Frame: baseline to Week 24 ]
  3. Change from baseline at Week 24 in PASI score [ Time Frame: baseline to Week 24 ]
  4. PASI improvement (%) from baseline at Week 24 [ Time Frame: baseline to Week 24 ]
  5. Change from baseline at Week 24 in affected body surface area (BSA) [ Time Frame: baseline to Week 24 ]

    The surface area of the subject'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%).


  6. Psoriasis Symptom Inventory (PSI) responder at Week 24 (total score ≤ 8, with no item scores > 1) [ Time Frame: Week 24 ]
    The PSI consists of eight psoriasis-specific questions. Subjects will be requested to rate 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.

  7. PSI total score of 0 at Week 24 [ Time Frame: Week 24 ]
  8. Number of symptom-free days from randomisation to Week 24 (symptom-free day = daily total PSI of 0 on that day) [ Time Frame: baseline to Week 24 ]
  9. Burden of symptoms assessed as the normalised area under the curve (AUC) of PSI from baseline to the last available assessment [ Time Frame: baseline to Week 24 ]
  10. Change from baseline at Week 24 in Dermatology Life Quality Index (DLQI) total score [ Time Frame: baseline to Week 24 ]
    DLQI consists of 10 items addressing the subject'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.

  11. DLQI total score of 0 or 1 at Week 24 [ Time Frame: Week 24 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03331835


Contacts
Contact: Clinical Disclosure Specialist +45 4494 5888 disclosure@leo-pharma.com

Locations
Germany
Fachklinik Bad Bentheim Klinik für Dermatologie Recruiting
Bad Bentheim, Germany, 48455
Charité - Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie Psoriasis Studien Zentrum Recruiting
Berlin, Germany, 10117
Rothhaar Studien GmbH Dermatologisches Studienzentrum Recruiting
Berlin, Germany, 10783
Hautarztpraxis Dr. Wildfeuer Recruiting
Berlin, Germany, 13055
Klinikum Bielefeld Klinik für Dermatologie und Allergologie Recruiting
Bielefeld, Germany, 33647
Hauttumorzentrum Ruhr- Universität im St. Josef Hospital Recruiting
Bochum, Germany, 44791
Hautarztpraxis Dr. Niesmann und Dr. Othlinghaus Recruiting
Bochum, Germany, 44793
Universitätsklinikum Bonn (AöR) Klinik und Poliklinik für Dermatologie und Allergologie Recruiting
Bonn, Germany, 53127
Elbe Klinikum Buxtehude Klinik für Dermatologie Recruiting
Buxtehude, Germany, 21614
Rosenpark Research Recruiting
Darmstadt, Germany, 64283
Universitätsklinikum Carl Gustav Carus Klinik und Poliklinik für Dermatologie Recruiting
Dresden, Germany, 01307
Universitätsklinikum Erlangen Hautklinik Recruiting
Erlangen, Germany, 91054
Universitätsklinikum Frankfurt Klinik für Dermatologie Recruiting
Frankfurt, Germany, 60590
Derma-Study-Center-Friedrichshafen Recruiting
Friedrichshafen, Germany, 88045
Gemeinschaftspraxis Rotterdam & Kollegen Facharzt für Haut & Geschlechtskrankheiten Recruiting
Gelsenkirchen, Germany, 45883
Universitätsklinikum Hamburg-Eppendorf, Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen Recruiting
Hamburg, Germany, 20246
SCIderm GmbH Recruiting
Hamburg, Germany, 20354
Medizinische Hochschule Hannover Klinik für Dermatologie Allergologie und Venerologie Recruiting
Hannover, Germany, 30625
Universitäts-Hautklinik Heidelberg Recruiting
Heidelberg, Germany, 69120
Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Schleswig-Holstein, Campus Kiel Psoriasis-Zentrum Recruiting
Kiel, Germany, 24105
Exellenzzentrum Entzündungsmedizin (CCIM) Universitätsklinikum Schleswig-Holstein, Campus Lübeck Recruiting
Lübeck, Germany, 23538
University Medical Center Mainz Department of Dermatology and Allergy, Clinical Research Center Recruiting
Mainz, Germany, 55131
Universitätsklinikum Mannheim der Universität Heidelberg Klinik für Dermatologie, Venerologie und Allergologie Recruiting
Mannheim, Germany, 68167
Technische Universität München Klinik und Poliklinik für Dermatologie und Allergologie Recruiting
München, Germany, 80802
Klinische Forschung Osnabrück - Klifos Recruiting
Osnabrück, Germany, 49074
KLINIKUM VEST GmbH Knappschaftskrankenhaus Recklinghausen Klinik für Dermatologie und Allergologie Recruiting
Recklinghausen, Germany, 45657
Gemeinschaftspraxis Weber & Crainic Recruiting
Schweinfurt, Germany, 97421
Hautarztpraxis Dres. Leitz Recruiting
Stuttgart, Germany, 70178
University Medical Center University of Tübingen Recruiting
Tübingen, Germany, 72076
Hautarztpraxis Recruiting
Witten, Germany, 58453
Sponsors and Collaborators
LEO Pharma
Investigators
Study Director: Study Director LEO Pharma

Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT03331835     History of Changes
Other Study ID Numbers: LP0160-1327
2016-003867-21 ( EudraCT Number )
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies, Monoclonal
Dimethyl Fumarate
Immunologic Factors
Physiological Effects of Drugs
Dermatologic Agents
Immunosuppressive Agents