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

Primary Purpose

Plaque Psoriasis, Psoriasis Vulgaris, Psoriasis

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Brodalumab

Placebo

Guselkumab

About this trial

This is an interventional treatment trial for Plaque Psoriasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1 (brodalumab + dummy 1)

Arm 2 (guselkumab + dummy 2)

Arm 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.

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.

Outcomes

Primary Outcome Measures

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

Having 100% improvement from baseline in PASI score. The PASI 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 assesses 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 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 and/or more extensive condition.

Secondary Outcome Measures

Time to PASI 100 response

Time to having 100% improvement from baseline in PASI score. The PASI 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 assesses 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 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 and/or more extensive condition.

Time to PASI 90 response

Time to having 90% improvement from baseline in PASI score. The PASI 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 assesses 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 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 and/or more extensive condition.

Having PASI 100 response, assessed separately at Weeks 4, 8, and 28

Having PASI 90 response, assessed separately at Weeks 4, 8, 16, and 28

Having 90% improvement from baseline in PASI score. The PASI 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 assesses 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 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 and/or more extensive condition.

Having Investigator's Global Assessment (IGA) of 0, assessed separately at Week 16 and Week 28.

Having a score of 0 (clear) in IGA. The IGA is an instrument used in clinical trials to rate the severity of psoriasis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).

Having IGA of 0 or 1, assessed separately at Week 16 and Week 28.

Having a score of 0 (clear) or 1 (almost clear) in IGA. The IGA is an instrument used in clinical trials to rate the severity of psoriasis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).

Having Dermatology Life Quality Index (DLQI) total score of 0 or 1, assessed separately at Weeks 4, 8, 12, 16, 20, 24, and 28.

The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the participant's perception of the impact of their skin disease on different aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = 'not at all/not relevant'; 1 = 'a little'; 2 = 'a lot'; 3 = 'very much'). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.

Change in 36-Item Short Form Health Survey version 2 (SF-36v2) score from baseline, assessed separately at Weeks 4, 8, 16, and 28.

The SF-36v2 is a 36-item general health status assessment. Participants answer each question by selecting 1 of 3 to 6 categorical response options. The SF-36v2 yields scores for 8 health domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health) and 2 psychometrically derived summary scores (a physical component summary and a mental component summary).

Occurrence of treatment-emergent adverse events (AEs) from baseline to Week 28.

An adverse event is considered treatment-emergent if the onset occurred after the first administration of IMP or if the event started prior to the first administration of IMP and worsened in severity after the first administration of IMP.

Full Information

NCT ID

NCT04533737

First Posted

August 26, 2020

Last Updated

January 11, 2023

Sponsor

LEO Pharma

1. Study Identification

Unique Protocol Identification Number

NCT04533737

Brief Title

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

Acronym

COBRA

Official Title

Efficacy and Safety Comparison of Brodalumab Versus Guselkumab in Adult Subjects With Moderate-to-severe Plaque Psoriasis and Inadequate Response to Ustekinumab

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

November 11, 2020 (Actual)

Primary Completion Date

September 8, 2022 (Actual)

Study Completion Date

December 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

LEO Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

Detailed 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, assessors, and investigators are unaware of which treatment is given.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Plaque Psoriasis, Psoriasis Vulgaris, Psoriasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Brodalumab (1.5 mL) and guselkumab (1.0 mL) are in pre-filled syringes and packaged open-label. Dummy injections are used for blinding.

Allocation

Randomized

Enrollment

113 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1 (brodalumab + dummy 1)

Arm Type

Experimental

Arm 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.

Arm Title

Arm 2 (guselkumab + dummy 2)

Arm Type

Active Comparator

Arm 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.

Intervention Type

Biological

Intervention Name(s)

Brodalumab

Other Intervention Name(s)

Kyntheum®

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance

Intervention Type

Biological

Intervention Name(s)

Guselkumab

Other Intervention Name(s)

Tremfya®

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Week 16

Secondary Outcome Measure Information:

Title

Time to PASI 100 response

Description

Time Frame

up to 28 weeks

Title

Time to PASI 90 response

Description

Time Frame

up to 28 weeks

Title

Having PASI 100 response, assessed separately at Weeks 4, 8, and 28

Description

Time Frame

Weeks 4, 8, and 28

Title

Having PASI 90 response, assessed separately at Weeks 4, 8, 16, and 28

Description

Time Frame

Weeks 4, 8, 16, and 28

Title

Having Investigator's Global Assessment (IGA) of 0, assessed separately at Week 16 and Week 28.

Description

Having a score of 0 (clear) in IGA. The IGA is an instrument used in clinical trials to rate the severity of psoriasis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).

Time Frame

Weeks 16 and 28

Title

Having IGA of 0 or 1, assessed separately at Week 16 and Week 28.

Description

Time Frame

Weeks 16 and 28

Title

Having Dermatology Life Quality Index (DLQI) total score of 0 or 1, assessed separately at Weeks 4, 8, 12, 16, 20, 24, and 28.

Description

Time Frame

Weeks 4, 8, 12, 16, 20, 24, and 28.

Title

Change in 36-Item Short Form Health Survey version 2 (SF-36v2) score from baseline, assessed separately at Weeks 4, 8, 16, and 28.

Description

Time Frame

Weeks 4, 8, 16, and 28.

Title

Occurrence of treatment-emergent adverse events (AEs) from baseline to Week 28.

Description

Time Frame

From baseline to Week 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Expert

Organizational Affiliation

LEO Pharma

Official's Role

Study Director

Facility Information:

Facility Name

LEO Pharma Investigational Site

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

LEO Pharma Investigational Site

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

LEO Pharma Investigational Site

City

Herstal

ZIP/Postal Code

B-4040

Country

Belgium

Facility Name

LEO Pharma Investigational Site

City

Namur

ZIP/Postal Code

5000

Country

Belgium

Facility Name

LEO Pharma Investigational Site

City

Marseille

State/Province

Bouches-du-Rhône

ZIP/Postal Code

13285

Country

France

Facility Name

LEO Pharma Investigational Site

City

Martigues

State/Province

Bouches-du-Rhône

ZIP/Postal Code

13500

Country

France

Facility Name

LEO Pharma Investigational Site

City

Rouen

State/Province

Seine-Maritime 10

ZIP/Postal Code

76031

Country

France

Facility Name

LEO Pharma Investigational Site

City

Saint-Mandé

State/Province

Val-de-Marne

ZIP/Postal Code

94160

Country

France

Facility Name

LEO Pharma Investigational Site

City

Nice

ZIP/Postal Code

06000

Country

France

Facility Name

LEO Pharma Investigational Site

City

Toulouse

ZIP/Postal Code

31000

Country

France

Facility Name

LEO Pharma Investigational Site

City

Freiburg im Breisgau

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

79104

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Aachen

ZIP/Postal Code

52057

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Augsburg

ZIP/Postal Code

86163

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Bad Bentheim

ZIP/Postal Code

48455

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Bonn

ZIP/Postal Code

53127

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Bramsche

ZIP/Postal Code

49565

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Buxtehude

ZIP/Postal Code

21614

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Frankfurt am Main

ZIP/Postal Code

60590

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Hamburg

ZIP/Postal Code

20537

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Mainz

ZIP/Postal Code

55128

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Memmingen

ZIP/Postal Code

87700

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

LEO Pharma Investigational Site

City

Selters

ZIP/Postal Code

56242

Country

Germany

Facility Name

LEO Pharma Investigational Site 1

City

Athens

ZIP/Postal Code

16121

Country

Greece

Facility Name

LEO Pharma Investigational Site 2

City

Athens

ZIP/Postal Code

16121

Country

Greece

Facility Name

LEO Pharma Investigational Site

City

Nea Efkarpía

ZIP/Postal Code

56403

Country

Greece

Facility Name

LEO Pharma Investigational Site 1

City

Thessaloníki

ZIP/Postal Code

54643

Country

Greece

Facility Name

LEO Pharma Investigational Site 2

City

Thessaloníki

ZIP/Postal Code

54643

Country

Greece

Facility Name

LEO Pharma Investigational Site

City

Napoli

ZIP/Postal Code

80121

Country

Italy

Facility Name

LEO Pharma Investigational Site

City

Pisa

ZIP/Postal Code

56126

Country

Italy

Facility Name

LEO Pharma Investigational Site

City

Roma

ZIP/Postal Code

00133

Country

Italy

Facility Name

LEO Pharma Investigational Site

City

Rozzano

ZIP/Postal Code

20089

Country

Italy

Facility Name

LEO Pharma Investigational Site

City

Mieres

State/Province

Asturias

ZIP/Postal Code

33611

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Bilbao

State/Province

Vizcaya

ZIP/Postal Code

48013

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Alicante

ZIP/Postal Code

03010

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Barcelona

ZIP/Postal Code

08026

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Granada

ZIP/Postal Code

18016

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Madrid

ZIP/Postal Code

28031

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Pontevedra

ZIP/Postal Code

36003

Country

Spain

Facility Name

LEO Pharma Investigational Site

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Pharma Investigational Site

City

Solna

State/Province

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

LEO Pharma Investigational Site

City

Saint Gallen

ZIP/Postal Code

9007

Country

Switzerland

Facility Name

LEO Pharma Investigational Site

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

Facility Name

LEO Pharma Investigational Site

City

Bath

State/Province

Avon

ZIP/Postal Code

BA1 3NG

Country

United Kingdom

Facility Name

LEO Pharma Investigational Site

City

Dudley

State/Province

West Midlands

ZIP/Postal Code

DY1 2HQ

Country

United Kingdom

Facility Name

LEO Pharma investigational site

City

Leeds

State/Province

West Yorkshire

ZIP/Postal Code

LS7 4SA

Country

United Kingdom

Facility Name

LEO Pharma Investigational Site

City

London

ZIP/Postal Code

SW17 0QT

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified IPD can be made available to researchers in a closed environment for a specified period of time.

IPD Sharing Time Frame

Data is available to request after results of the trial are available on leopharmatrials.com

IPD Sharing Access Criteria

Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement

IPD Sharing URL

http://leopharmatrials.com/for-professionals

Learn more about this trial

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

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

Plaque Psoriasis, Psoriasis Vulgaris, Psoriasis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial