Adjusted Brodalumab Dose Compared With Standard Brodalumab Dose in Subjects With Moderate-to-severe Plaque Psoriasis and ≥120 kg Body Weight (ADJUST)

LEO Pharma

Status and phase: Active, not recruiting; Phase 4

Conditions: Psoriasis Vulgaris

Treatments: Biological: Brodalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04306315

2023-509668-11-00 (EU Trial (CTIS) Number)

U1111-1282-4507 (Other Identifier)

2017-004998-13 (EudraCT Number)

LP0160-1329

Details and patient eligibility

About

This study investigates if an adjusted brodalumab dosage regimen will give improved efficacy in psoriasis in patients with a body weight of over 120 kg. The increased dosage regimen will be compared to the standard brodalumab treatment plus placebo.

Full description

Brodalumab is an anti-IL-17 receptor antibody and blocks the inflammatory effects of IL-17 in the skin. Some psoriasis patients with a higher body weight experienced a lower treatment effect of brodalumab in clinical studies. Therefore, the purpose of this study is to investigate if increasing the dose of brodalumab will increase the effect of treatment for patients with a higher body weight. The study will run over 60-62 weeks, including screening, treatment period and safety follow-up, with the primary endpoint measurement at Week 40. Patients will receive subcutaneous injections of brodalumab at Week 0, 1, and 2, followed by injections every 2 weeks. Participants not fulfilling a predefined response at any time after Week 16 will receive a dose adjustment to 280 mg brodalumab or 210 mg brodalumab plus placebo every 2 weeks.

Enrollment: 385 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Signed and dated informed consent has been obtained prior to any protocol-related procedures.
• Age ≥18 to <75 years at the time of screening.
• Diagnosed with chronic plaque psoriasis at least 6 months before randomisation.
• Body weight ≥120 kg at the time of screening.
• Moderate-to-severe plaque psoriasis as defined by: BSA ≥10% and PASI ≥12 at screening and baseline.
• No evidence of active or latent tuberculosis according to local standard of care.

Key Exclusion Criteria:

• Diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g., eczema) that would interfere with evaluations of the effect of the investigational medicinal product (IMP) on participants with plaque psoriasis.
• Clinically important active infections or infestations, chronic, recurrent or latent infections or infestations, or is immunocompromised (e.g., human immunodeficiency virus, hepatitis B, and hepatitis C).
• Any systemic disease considered by the investigator to be uncontrolled and either immunocompromising the participants and/or placing the participant at undue risk of intercurrent diseases (including, but not limited to, renal failure, heart failure, liver disease, diabetes, and anaemia).
• History of Crohn's disease.
• Myocardial infarction or stroke, or unstable angina pectoris within the past 12 months.
• Any active malignancy.
• History of malignancy within 5 years, except for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma.
• History of suicidal behaviour (i.e., 'actual suicide attempt', 'interrupted attempt', 'aborted attempt', or 'preparatory acts or behaviour') based on the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at screening or at baseline.
• Any suicidal ideation of category 4 or 5 ('active suicidal ideation with some intent to act, without specific plan' or ' active suicidal ideation with specific plan and intent') based on the C-SSRS questionnaire at screening or at baseline.
• A Patient Health Questionnaire (PHQ)-8 score of ≥10 corresponding to moderate-to-severe depression at screening or at baseline.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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385 participants in 2 patient groups, including a placebo group

Brodalumab 210 mg + brodalumab 70 mg add-on* (adjusted brodalumab dosing regimen)

Experimental group

Description:

Participants will receive 210 mg brodalumab subcutaneously at Week 0, Week 1, and Week 2, and then once every 2 weeks. \*Participants not fulfilling a predefined response at any visit with efficacy assessments after Week 16 will receive a dose adjustment to 280 mg brodalumab every 2 weeks.

Treatment:

Biological: Brodalumab

Brodalumab 210 mg + placebo add-on* (standard brodalumab treatment)

Placebo Comparator group

Description:

Participants will receive 210 mg brodalumab subcutaneously at Week 0, Week 1, and Week 2, and then once every 2 weeks. \*Participants not fulfilling a predefined response at any time visit with efficacy assessments Week 16 will receive a dose adjustment to 210 mg brodalumab + placebo every 2 weeks.

Treatment:

Biological: Brodalumab