Efficacy and Safety of Brodalumab Compared With Guselkumab in the Treatment of Plaque Psoriasis After Inadequate Response to Ustekinumab (COBRA)
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| ClinicalTrials.gov Identifier: NCT04533737 |
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Recruitment Status :
Completed
First Posted : September 1, 2020
Last Update Posted : January 12, 2023
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Sponsor:
LEO Pharma
Information provided by (Responsible Party):
LEO Pharma
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Plaque Psoriasis Psoriasis Vulgaris Psoriasis | Biological: Brodalumab Other: Placebo Biological: Guselkumab | Phase 4 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 113 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes 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. |
| Primary Purpose: | Treatment |
| Official Title: | Efficacy and Safety Comparison of Brodalumab Versus Guselkumab in Adult Subjects With Moderate-to-severe Plaque Psoriasis and Inadequate Response to Ustekinumab |
| Actual Study Start Date : | November 11, 2020 |
| Actual Primary Completion Date : | September 8, 2022 |
| Actual Study Completion Date : | December 1, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm 1 (brodalumab + dummy 1)
Participants receive:
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Biological: Brodalumab
Pre-filled syringe with 210 mg brodalumab in 1.5 ml solution for subcutaneous injection
Other Name: Kyntheum® Other: Placebo The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance |
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Active Comparator: Arm 2 (guselkumab + dummy 2)
Participants receive:
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Other: Placebo
The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance Biological: Guselkumab Pre-filled syringe with 100 mg guselkumab in 1 ml solution for subcutaneous injection
Other Name: Tremfya® |
Primary Outcome Measures :
- Having Psoriasis Area and Severity Index (PASI) 100 response at Week 16 [ Time Frame: 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 Frame: up to 28 weeks ]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 Frame: up to 28 weeks ]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 [ Time Frame: Weeks 4, 8, and 28 ]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.
- Having PASI 90 response, assessed separately at Weeks 4, 8, 16, and 28 [ Time Frame: 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. [ Time Frame: Weeks 16 and 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. [ Time Frame: Weeks 16 and 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04533737
Locations
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Sponsors and Collaborators
LEO Pharma
Investigators
| Study Director: | Medical Expert | LEO Pharma |
| Responsible Party: | LEO Pharma |
| ClinicalTrials.gov Identifier: | NCT04533737 |
| Other Study ID Numbers: |
LP0160-1510 2019-004099-20 ( EudraCT Number ) U1111-1283-7584 ( Other Identifier: World Health Organization (WHO) ) |
| First Posted: | September 1, 2020 Key Record Dates |
| Last Update Posted: | January 12, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | De-identified IPD can be made available to researchers in a closed environment for a specified period of time. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data is available to request after results of the trial are available on leopharmatrials.com |
| Access Criteria: | Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement |
| URL: | http://leopharmatrials.com/for-professionals |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
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Psoriasis Skin Diseases, Papulosquamous Skin Diseases Brodalumab Dermatologic Agents |