Adjustable Brodalumab Dosage Regimen Compared With Standard Brodalumab Treatment for 52 Weeks in Subjects With Moderate-to-severe Plaque Psoriasis and ≥120 kg Body Weight
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- LEO Pharma
- Enrollment
- 385
- Locations
- 82
- Primary Endpoint
- Having at least 90% lower Psoriasis Area and Severity Index (PASI) score relative to baseline (PASI 90 response) at Week 40.
Study Overview
Brief Summary
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
The pre-filled syringes with 210 mg (1.5 mL) brodalumab will be open-label. The packaging and labelling of the pre-filled syringes with 70 mg (0.5 mL) brodalumab or placebo will contain no evidence to distinguish brodalumab from placebo. It is not considered possible to distinguish between brodalumab and placebo visually; both solutions are colourless.
Eligibility Criteria
- Ages
- 18 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Arms & Interventions
Brodalumab 210 mg + brodalumab 70 mg add-on* (adjusted brodalumab dosing regimen)
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.
Intervention: Brodalumab (Biological)
Brodalumab 210 mg + placebo add-on* (standard brodalumab treatment)
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.
Intervention: Brodalumab (Biological)
Outcomes
Primary Outcomes
Having at least 90% lower Psoriasis Area and Severity Index (PASI) score relative to baseline (PASI 90 response) at Week 40.
Time Frame: Week 40
The PASI score is the most widely used tool in clinical practice and clinical trials to assess the severity and extent of psoriasis. The assessment is done based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. The investigator will assess the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions, head/neck, trunk, upper extremities, and lower extremities, according to a severity scale. The investigator will also assess the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0-72, with higher values indicating a more severe and/or more extensive condition.
Secondary Outcomes
- Having sPGA of genitalia (sPGA-G) score of 0 or 1 at Week 40(Week 40)
- Having sPGA-G score of 0 or 1 at Week 52(Week 52)
- Change from baseline at Weeks 40 and 52 in PASI score(Week 40 and 52)
- Having PASI 90 response at Week 52(Week 52)
- Having PASI 100 response at Week 52(Week 52)
- Change from baseline at Weeks 40 and 52 in DLQI total score(Week 40 and 52)
- Having static Physician's Global Assessment (sPGA) score of 0 or 1 at Week 40(Week 40)
- Having sPGA score of 0 or 1 at Week 52(Week 52)
- Having sPGA of genitalia (sPGA-G) score of 0 or 1 at both Week 40 and Week 52(Week 40)
- Having PASI 100 response at Week 40(Week 40)
- Change from baseline at Weeks 40 and 52 in affected body surface area (BSA)(Week 40 and 52)
- Number of Participants Experiencing Adverse Events (AEs) up to Week 58.(Week 58)
- Having Dermatology Life Quality Index (DLQI) total score of 0 or 1 at Week 40(Week 40)
- Having DLQI total score of 0 or 1 at Week 52(Week 52)
- Having sPGA of genitalia (sPGA-G) score of 0 or 1 at both Week 40 and Week 52(Week 40 and 52)