Efficacy and Safety of Brodalumab Compared With Guselkumab in the Treatment of Plaque Psoriasis After Inadequate Response to Ustekinumab (COBRA)

LEO Pharma

Status and phase: Terminated; Phase 4

Conditions: Psoriasis; Plaque Psoriasis; Psoriasis Vulgaris

Treatments: Biological: Guselkumab; Other: Placebo; Biological: Brodalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04533737

LP0160-1510

2019-004099-20 (EudraCT Number)

U1111-1283-7584 (Other Identifier)

Details and patient eligibility

About

The trial investigates the efficacy and safety of brodalumab against guselkumab in treatment for patients with moderate-to-severe plaque psoriasis who still have some remaining symptoms after ustekinumab treatment.

Full description

Brodalumab is an anti-interleukin 17 receptor A antibody (IL-17RA) and blocks the inflammatory effects of different IL-17 cytokines (IL-17A, IL-17C, IL-17F, IL-17A/F heterodimer, and IL-17E) in the skin. With increasing availability of novel biologics with new targets, the complexity of choosing the appropriate biologic treatment is ever more challenging for physicians. Therefore, the primary objective of this trial is to compare the efficacy of brodalumab versus guselkumab in adult participants with moderate to severe plaque psoriasis and inadequate response to ustekinumab, thereby providing new scientific information that could support decision making in the clinical setting. The study will run approximately 32 weeks for each participant (including a 2- to 4-weeks screening period and a 28-week treatment period), with the primary endpoint measurement at Week 16. Participants receive subcutaneous injections of brodalumab or guselkumab. Dummy injections are also given, so participants and assessors are unaware of which treatment is given.

Enrollment: 113 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participant has a diagnosis of plaque psoriasis for at least 6 months before the first administration of investigational medicinal product (IMP) as determined by the investigator.

• Participant has inadequately controlled plaque psoriasis currently treated with ustekinumab, and fulfils ALL of the following criteria:

  1. Ustekinumab administered at least 3 times at or higher than the approved dose or frequency before randomisation.
  2. IGA ≥2 at screening and baseline.
  3. Absolute PASI >3 at screening and baseline.

• Participant has no evidence of active tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment. Participants with adequately treated latent tuberculosis, according to local guidelines, are eligible.

Key Exclusion Criteria:

• Participant was 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 IMP on plaque psoriasis.
• Participant has clinically important active infections or infestations, chronic, recurrent, or latent infections or infestations, or is immunocompromised (e.g. human immunodeficiency virus).
• Participant has any systemic disease (e.g. renal failure, heart failure, hypertension, liver disease, diabetes, anaemia) considered by the investigator to be clinically significant and uncontrolled.
• Participant has a known history of Crohn's disease.
• Participant has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
• Participant has a 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.
• Participant has a known history of active tuberculosis.
• Participant has a 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 baseline.
• Participant has any suicidal ideation of severity 4 or 5 ('some intent to act, no plan' or 'specific plan and intent') based on the C-SSRS questionnaire at screening or baseline.
• Participant has a Patient Health Questionnaire-8 (PHQ-8) score of ≥10, corresponding to moderate to severe depression at screening or baseline.
• Participant has previously been treated with any anti-interleukin (IL)-17A, anti-IL 17 receptor subunit A, or anti-IL-23 besides ustekinumab.
• Participant has known or suspected hypersensitivity to any component(s) of the IMPs.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

113 participants in 2 patient groups

Arm 1 (brodalumab + dummy 1)

Experimental group

Description:

Participants receive: * Brodalumab 210 mg (1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks. * Dummy 1 (placebo 1.0 ml) at Weeks 0, 4, and then every 8 weeks.

Treatment:

Other: Placebo

Biological: Brodalumab

Arm 2 (guselkumab + dummy 2)

Active Comparator group

Description:

Participants receive: * Guselkumab 100 mg (1.0 ml) at Weeks 0, 4, and then every 8 weeks. * Dummy 2 (placebo 1.5 ml) at Weeks 0, 1, 2, and then every 2 weeks.

Treatment:

Other: Placebo

Biological: Guselkumab