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 Pharma

Status and phase: Completed; Phase 4

Conditions: Psoriasis Vulgaris

Treatments: Drug: Fumaric acid esters; Biological: Brodalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03331835

LP0160-1327

2016-003867-21 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 210 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

210 participants in 2 patient groups

Brodalumab

Experimental group

Description:

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).

Treatment:

Biological: Brodalumab

Fumaric acid esters

Active Comparator group

Description:

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.

Treatment:

Drug: Fumaric acid esters