Efficacy and safety of brodalumab compared with guselkumab in the treatment of plaque psoriasis after inadequate response to ustekinumab.

Phase 1

• Conditions: adult subjects with moderate-to-severe plaque psoriasis; MedDRA version: 20.0Level: LLTClassification code 10071117Term: Plaque psoriasisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2019-004099-20-GR
• Lead Sponsor: EO Pharma A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-15
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

- Subject is i:!:18 years of age at the time of screening.
- Subject 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.
- Subject has inadequately controlled plaque psoriasis currently treated
with ustekinumab, and fulfil ALL of the following criteria:
- Ustekinumab administered at least 3 times at or higher than the
approved dose or frequency before randomisation.
- IGA i:!:2 at screening and baseline.
- Absolute PASI >3 at screening and baseline.
- Subject has no evidence of active tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment. Subjects with adequately treated latent tuberculosis, according to local guidelines, are eligible.
a.DA tuberculosis test can be performed at the central laboratory.
b.?If a local laboratory test is performed to confirm this criterium, the local laboratory should be assessed before the local testing is performed.
- Subject who is a woman of childbearing potential* must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
* A woman is defined as being of childbearing potential if she is not postmenopausal (at least 12 months with no menses without an alternative medical cause prior to screening) and not surgically sterile
(hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
- Subject who is a woman of childbearing potential* must use a highly effective** form of birth control throughout the trial and at least for 12 weeks after last administration of IMP.
** A highly effective method of birth control is defined as one which results in a low failure rate (less than 10/o per year) such as bilateral tubal occlusion, intrauterine device, intrauterine hormone-releasing system, combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), sexual abstinence (when this is in line with the preferred and usual life style of the subject), or vasectomised partner (given that the subject is monogamous).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

- Subject 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.
- Subject has clinically important active infections or infestations, chronic, recurrent, or latent infections or infestations, or is immunocompromised (e.g. human immunodeficiency virus).
- Subject 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.
- Subject has a known history of Crohn’s disease.
- Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
- Subject 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.
- Subject has a known history of active tuberculosis.
- Subject 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 (CSSRS) questionnaire at screening or baseline.
- Subject 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.
- Subject has a Patient Health Questionnaire-8 (PHQ-8) score of =10, corresponding to moderate-to-severe depression at screening or baseline.
- -Subject has previously received more than 1 tumour necrosis factor-a (TNF-a) inhibitor. NOTE: This exclusion criterion is not applicable in this version of the protocol. It is kept to avoid re-numbering of the exclusion criteria.
-Subject has previously received more than 1 tumour necrosis factor-a (TNF-a) inhibitor. NOTE: This exclusion criterion is not applicable in this version of the protocol. It is kept to avoid re-numbering of the exclusion criteria.
- Subject has previously been treated with any anti-interleukin (IL)-17A, anti-IL-17 receptor subunit A, or anti-IL-23 besides ustekinumab.
- Subject has known or suspected hypersensitivity to any component(s) of the IMPs.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of brodalumab with guselkumab in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.;Secondary Objective: To evaluate the efficacy of brodalumab compared with guselkumab while ontreatment for up to 28 weeks in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.<br><br>To evaluate the efficacy of brodalumab compared with guselkumab through Week 28 in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.<br><br>To evaluate the safety of brodalumab compared with guselkumab throughout the trial (28 weeks) in adult subjects with moderate-to-severe plaque psoriasis and prior inadequate response to ustekinumab.;Primary end point(s): Primary endpoint:<br>Having PASI 100 response at Week 16.<br>;Timepoint(s) of evaluation of this end point: At week 16

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key secondary endpoint:<br>Time to PASI 100 response<br><br>Secondary endpoints:<br>Time to PASI 90 response<br>Having PASI 100 response, assessed separately at Weeks 4, 8, and 28.<br>Having PASI 90 response, assessed separately at Weeks 4, 8, 16, and 28.<br>Having IGA of 0, assessed separately at Week 16 and Week 28.<br>Having IGA of 0 or 1, assessed separately at Week 16 and Week 28.<br>Having DLQI total score of 0 or 1, assessed separately at Weeks 4, 8, 12, 16, 20, 24, and 28.<br>Change in SF-36v24 score from baseline, assessed separately at Weeks 4, 8, 16, and 28.<br>Occurrence of TEAEs from baseline to Week 28.;Timepoint(s) of evaluation of this end point: Between week 0 and 28, as specified for each endpoint.