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

NCT04533737 | Terminated Phase 4 Results FDA Drug

• 3 other identifiers: LP0160-15102019-004099-20U1111-1283-7584
• Study Type: interventional
• Target: 113
• Locations: 12 countries
• Sites: 65

Brief Summary

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.

Conditions

Plaque Psoriasis; Psoriasis Vulgaris; Psoriasis

Outcome Measures

Primary Outcomes (1)

• Having Psoriasis Area and Severity Index (PASI) 100 Response at Week 16

  Having 100% improvement from baseline in PASI score. The outcome measure is summarized using the least squares mean percentage of subjects having PASI 100 response at Week 16, based on a logistic regression model adjusted for baseline body weight (\<=100 kg,\>100 kg) and baseline PASI score. The PASI is the most widely used tool in clinical practice and clinical trials to assess psoriasis severity and extent. Assessment is done based on the condition of the disease at the time of evaluation, not in relation to the condition at a previous visit. The investigator assesses the severity of 3 psoriasis disease characteristics (redness, thickness, and scaliness) on each of the 4 body regions (head/neck, trunk, upper extremities, lower extremities) according to a severity scale. The investigator also assesses the extent of psoriasis within each of the 4 body regions. This gives a composite score ranging from 0 to 72, with higher values indicating a more severe/extensive condition.

  Week 16

Secondary Outcomes (10)

• Time to PASI 100 Response (Summarized as the Cumulative Incidence for Achieving PASI 100 at Each Timepoint, Stratified by Weight)

  up to 28 weeks

• Time to PASI 90 Response (Summarized as the Cumulative Incidence for Achieving PASI 90 at Each Timepoint, Stratified by Weight)

  up to 28 weeks

• Having PASI 100 Response, Assessed Separately at Weeks 4, 8, and 28.

  Weeks 4, 8, and 28

• Having PASI 90 Response, Assessed Separately at Weeks 4, 8, 16, and 28.

  Weeks 4, 8, 16, and 28

• Having Investigator's Global Assessment (IGA) of 0, Assessed Separately at Weeks 16 and 28.

  Weeks 16 and 28

Study Arms (2)

Arm 1 (brodalumab + dummy 1)

EXPERIMENTAL

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.

Biological: Brodalumab; Other: Placebo

Arm 2 (guselkumab + dummy 2)

ACTIVE COMPARATOR

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.

Other: Placebo; Biological: Guselkumab

Interventions

Brodalumab BIOLOGICAL

Pre-filled syringe with 210 mg brodalumab in 1.5 ml solution for subcutaneous injection

Also known as: Kyntheum®

Arm 1 (brodalumab + dummy 1)

Placebo OTHER

The placebo solution is similar to the active guselkumab (Dummy 1) or brodalumab (Dummy 2) solution except that it does not contain any active substance

Also known as: Dummy 1/Dummy 2

Arm 1 (brodalumab + dummy 1); Arm 2 (guselkumab + dummy 2)

Guselkumab BIOLOGICAL

Pre-filled syringe with 100 mg guselkumab in 1 ml solution for subcutaneous injection

Also known as: Tremfya®

Arm 2 (guselkumab + dummy 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Ustekinumab administered at least 3 times at or higher than the approved dose or frequency before randomisation.
• IGA ≥2 at screening and baseline.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (65)

LEO Pharma Investigational Site

Graz, Styria, 8036, Austria

Location

LEO Pharma Investigational Site

Vienna, 1090, Austria

Location

LEO Pharma Investigational Site

Brussels, 1200, Belgium

Location

LEO Pharma Investigational Site

Herstal, 4040, Belgium

Location

LEO Pharma Investigational Site

Namur, 5000, Belgium

Location

LEO Pharma Investigational Site

Copenhagen, 2400, Denmark

Location

LEO Pharma Investigational Site

Hellerup, 2900, Denmark

Location

LEO Pharma Investigational Site

Roskilde, 4000, Denmark

Location

LEO Pharma Investigational Site

Marseille, Bouches-du-Rhône, 13008, France

Location

LEO Pharma Investigational Site

Martigues, Bouches-du-Rhône, 13500, France

Location

LEO Pharma Investigational Site

Rouen, Seine-Maritime 10, 76031, France

Location

LEO Pharma Investigational Site

Saint-Mandé, Val-de-Marne, 94160, France

Location

LEO Pharma Investigational Site

Antony, 92160, France

Location

LEO Pharma Investigational Site

Nice, 06000, France

Location

LEO Pharma Investigational Site

Saint-Priest-en-Jarez, 42277, France

Location

LEO Pharma Investigational Site

Toulouse, 31059, France

Location

LEO Pharma Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79104, Germany

Location

LEO Pharma Investigational Site

Aachen, 52074, Germany

Location

LEO Pharma Investigational Site

Augsburg, 86163, Germany

Location

LEO Pharma Investigational Site

Bad Bentheim, 48455, Germany

Location

LEO Pharma Investigational Site

Bonn, 53127, Germany

Location

LEO Pharma Investigational Site

Bramsche, 49565, Germany

Location

LEO Pharma Investigational Site

Buxtehude, 21614, Germany

Location

LEO Pharma Investigational Site

Cologne, 50937, Germany

Location

LEO Pharma Investigational Site

Darmstadt, 64297, Germany

Location

LEO Pharma Investigational Site

Erlangen, 91054, Germany

Location

LEO Pharma Investigational Site

Frankfurt am Main, 60590, Germany

Location

LEO Pharma Investigational Site

Hamburg, 20246, Germany

Location

LEO Pharma Investigational Site

Hamburg, 20537, Germany

Location

LEO Pharma Investigational Site

Kiel, 24105, Germany

Location

LEO Pharma Investigational Site

Mainz, 55128, Germany

Location

LEO Pharma Investigational Site

Mainz, 55131, Germany

Location

LEO Pharma Investigational Site

Memmingen, 87700, Germany

Location

LEO Pharma Investigational Site

Munich, 80802, Germany

Location

LEO Pharma Investigational Site

Münster, 48149, Germany

Location

LEO Pharma Investigational Site

Selters, 56242, Germany

Location

LEO Pharma Investigational Site 1

Athens, 16121, Greece

Location

LEO Pharma Investigational Site 2

Athens, 16121, Greece

Location

LEO Pharma Investigational Site 1

Thessaloniki, 54643, Greece

Location

LEO Pharma Investigational Site 2

Thessaloniki, 54643, Greece

Location

LEO Pharma Investigational Site

Thessaloniki, 54643, Greece

Location

LEO Pharma Investigational Site

Napoli, 80121, Italy

Location

LEO Pharma Investigational Site

Pisa, 56126, Italy

Location

LEO Pharma Investigational Site

Roma, 00133, Italy

Location

LEO Pharma Investigational Site

Rozzano, 20089, Italy

Location

LEO Pharma Investigational Site

Bergen op Zoom, Bergen, 4614 VT, Netherlands

Location

LEO Pharma Investigational Site

Almere Stad, RL Almere, 1311, Netherlands

Location

LEO Pharma Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

LEO Pharma Investigational Site

Mieres, Principality of Asturias, 33611, Spain

Location

LEO Pharma Investigational Site

Bilbao, Vizcaya, 48013, Spain

Location

LEO Pharma Investigational Site

Alicante, 03010, Spain

Location

LEO Pharma Investigational Site

Barcelona, 08036, Spain

Location

LEO Pharma Investigational Site

Barcelona, 08041, Spain

Location

LEO Pharma Investigational Site

Granada, 18016, Spain

Location

LEO Pharma Investigational Site

Madrid, 28031, Spain

Location

LEO Pharma Investigational Site

Madrid, 28041, Spain

Location

LEO Pharma Investigational Site

Pontevedra, 36001, Spain

Location

LEO Pharma Investigational Site

Valencia, 46026, Spain

Location

LEO Pharma Investigational Site

Solna, Stockholm County, 171 76, Sweden

Location

LEO Pharma Investigational Site

Sankt Gallen, 9007, Switzerland

Location

LEO Pharma Investigational Site

Zurich, 8091, Switzerland

Location

LEO Pharma Investigational Site

Bath, Avon, BA1 3NG, United Kingdom

Location

LEO Pharma Investigational Site

Dudley, West Midlands, DY1 2HQ, United Kingdom

Location

LEO Pharma investigational site

Leeds, West Yorkshire, LS7 4SA, United Kingdom

Location

LEO Pharma Investigational Site

London, SW17 0RE, United Kingdom

Location

Related Publications (1)

• Reich K, Bianchi L, Khemis A, Maul JT, Tsianakas A, Schempp CM, Petersen K, Noergaard MM, Puig L. Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA). Dermatol Ther (Heidelb). 2024 Feb;14(2):453-468. doi: 10.1007/s13555-023-01092-x. Epub 2024 Feb 1.

  PMID: 38300408 RESULT

MeSH Terms

Conditions

Psoriasis

Interventions

brodalumab; guselkumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Clinical Disclosure
• Organization: LEO Pharma A/S

disclosure@leo-pharma.com

+45 44 94 58 88

Study Officials

• Medical Expert

  LEO Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Brodalumab (1.5 mL) and guselkumab (1.0 mL) are in pre-filled syringes and packaged open-label. Dummy injections are used for blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: September 1, 2020
• Study Start: December 17, 2020
• Primary Completion: September 8, 2022
• Study Completion: December 7, 2022
• Last Updated: March 14, 2025
• Results First Posted: January 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); DE (20); NL (3); ES (10); CH (2); IT (4); BE (3); AU (2); GR (5); DK (3); FR (8); SE (1)