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

Sponsor
LEO Pharma (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04533737
Collaborator
(none)
240
Enrollment
55
Locations
2
Arms
40.2
Anticipated Duration (Months)
4.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Brodalumab
  • Other: Placebo
  • Biological: Guselkumab
 Phase 4

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
240 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 :
Nov 11, 2020
Anticipated Primary Completion Date :
Jul 31, 2023
Anticipated Study Completion Date :
Mar 18, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1 (brodalumab + dummy 1)

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
Pre-filled syringe with 210 mg brodalumab in 1.5 ml solution for subcutaneous injection
Other Names:
  • Kyntheum®

    • Other: Placebo
    The placebo solution is similar to the active brodalumab solution except that it does not contain any active substance
    Active Comparator: Arm 2 (guselkumab + dummy 2)

    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
    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 Names:
  • Tremfya®

    		•

    Outcome Measures

    Primary Outcome Measures

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

    1. Time to PASI 100 response [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.

    2. Time to PASI 90 response [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.

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

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

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

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

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

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

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 LEO Pharma Investigational Site Graz Steiermark Austria 8036
    2 LEO Pharma Investigational Site Wien Austria 1090
    3 LEO Pharma Investigational Site Brussels Belgium 1200
    4 LEO Pharma Investigational Site Herstal Belgium B-4040
    5 LEO Pharma Investigational Site Namur Belgium 5000
    6 LEO Pharma Investigational Site Marseille Bouches-du-Rhône France 13285
    7 LEO Pharma Investigational Site Martigues Bouches-du-Rhône France 13500
    8 LEO Pharma Investigational Site Rouen Seine-Maritime 10 France 76031
    9 LEO Pharma Investigational Site Saint-Mandé Val-de-Marne France 94160
    10 LEO Pharma Investigational Site Antony France 92160
    11 LEO Pharma Investigational Site Nice France 06000
    12 LEO Pharma Investigational Site Toulouse France 31000
    13 LEO Pharma Investigational Site Freiburg im Breisgau Baden-Wuerttemberg Germany 79104
    14 LEO Pharma Investigational Site Aachen Germany 52057
    15 LEO Pharma Investigational Site Augsburg Germany 86163
    16 LEO Pharma Investigational Site Bad Bentheim Germany 48455
    17 LEO Pharma Investigational Site Bonn Germany 53127
    18 LEO Pharma Investigational Site Bramsche Germany 49565
    19 LEO Pharma Investigational Site Buxtehude Germany 21614
    20 LEO Pharma Investigational Site Erlangen Germany 91054
    21 LEO Pharma Investigational Site Frankfurt am Main Germany 60590
    22 LEO Pharma Investigational Site Hamburg Germany 20246
    23 LEO Pharma Investigational Site Hamburg Germany 20537
    24 LEO Pharma Investigational Site Kiel Germany 24105
    25 LEO Pharma Investigational Site Mainz Germany 55128
    26 LEO Pharma Investigational Site Mainz Germany 55131
    27 LEO Pharma Investigational Site Memmingen Germany 87700
    28 LEO Pharma Investigational Site Münster Germany 48149
    29 LEO Pharma Investigational Site Selters Germany 56242
    30 LEO Pharma Investigational Site 1 Athens Greece 16121
    31 LEO Pharma Investigational Site 2 Athens Greece 16121
    32 LEO Pharma Investigational Site Nea Efkarpia Greece 56403
    33 LEO Pharma Investigational Site 1 Thessaloníki Greece 54643
    34 LEO Pharma Investigational Site 2 Thessaloníki Greece 54643
    35 LEO Pharma Investigational Site Napoli Italy 80121
    36 LEO Pharma Investigational Site Pisa Italy 56126
    37 LEO Pharma Investigational Site Roma Italy 00133
    38 LEO Pharma Investigational Site Rozzano Italy 20089
    39 LEO Pharma Investigational Site Mieres Asturias Spain 33611
    40 LEO Pharma Investigational Site Bilbao Vizcaya Spain 48013
    41 LEO Pharma Investigational Site Alicante Spain 03010
    42 LEO Pharma Investigational Site Barcelona Spain 08026
    43 LEO Pharma Investigational Site Barcelona Spain 08036
    44 LEO Pharma Investigational Site Granada Spain 18016
    45 LEO Pharma Investigational Site Madrid Spain 28031
    46 LEO Pharma Investigational Site Madrid Spain 28041
    47 LEO Pharma Investigational Site Pontevedra Spain 36003
    48 LEO Pharma Investigational Site Valencia Spain 46026
    49 Pharma Investigational Site Solna Stockholm Sweden 171 76
    50 LEO Pharma Investigational Site Saint Gallen Switzerland 9007
    51 LEO Pharma Investigational Site Zürich Switzerland 8091
    52 LEO Pharma Investigational Site Bath Avon United Kingdom BA1 3NG
    53 LEO Pharma Investigational Site Dudley West Midlands United Kingdom DY1 2HQ
    54 LEO Pharma investigational site Leeds West Yorkshire United Kingdom LS7 4SA
    55 LEO Pharma Investigational Site London United Kingdom SW17 0QT

    Sponsors and Collaborators

    • LEO Pharma

    Investigators

    • Study Director: Medical Expert, LEO Pharma

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    LEO Pharma
    ClinicalTrials.gov Identifier:
    NCT04533737
    Other Study ID Numbers:
    • LP0160-1510
    • 2019-004099-20
    First Posted:
    Sep 1, 2020
    Last Update Posted:
    Jul 13, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:
    Psoriasis
    Brodalumab

    Study Results

    No Results Posted as of Jul 13, 2022