Primary objectiveTo compare the efficacy of brodalumab with guselkumab in adult subjects with moderate to severe plaque psoriasis and prior inadequate response to ustekinumab. Secondary objectives:To evaluate the efficacy of brodalumab compared with…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Having PASI (psoriasis area severity index) 100 response at Week 16.
Secondary outcome
Key secondary endpoint:
• Time to PASI 100 response.
Additional Secondary endpoints:
Time to PASI 90 response.
• 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 IGA (Investigator Global Assessment) of 0, assessed separately at Week
16 and Week 28.
• Having IGA of 0 or 1, assessed separately at Week 16 and Week 28.
• Having Dermatology Life Quality Index (DLQI) total score of 0 or 1, assessed
separately at Weeks 4, 8, 12, 16, 20, 24, and 28.
• Change in Short Form Health Survey version 2 (SF-36v2) score from baseline,
assessed separately at Weeks 4, 8, 16, and 28.
Occurrence of treatment-emergent adverse event(TEAEs)from baseline to Week 28.
Background summary
Psoriasis is a chronic immune-mediated inflammatory disease characterised by
patches of red, dry, itchy, and scaly skin, occurring in approximately 2% of
the population worldwide. Plaque psoriasis is the most common type of
psoriasis, corresponding to approximately 90% of all types.
Current data revealed that the main pathophysiological driver is the
interleukin 23 (IL 23)/T helper (Th) 17 cell axis. Th17 cells are activated by
IL 23, thereby producing vast amounts of proinflammatory cytokines (e.g. IL
17A, tumour necrosis factor α [TNF α], IL 22, and IL 17F). IL 17A and IL 17F
bind to the IL 17 receptor subunit A (IL 17RA), which generates the
inflammatory response that causes keratinocytes to proliferate, leading to the
formation of psoriatic plaques.
Within the last decades, biologic therapies targeting different steps of the
pathway have been introduced. This led to a revolution in the treatment
paradigm of moderate to severe plaque psoriasis and made complete clearance of
the skin a realistic treatment goal.
Despite the improved treatment options, it is well recognised that patients may
have an inadequate response to biologics due to a variety of reasons, including
initial lack of efficacy (primary failures), loss of efficacy over time
(secondary failures), and the advent of adverse events (AEs) or
contraindications to the therapy. Hence, comparisons between therapies after a
biologic failure could provide more data which can facilitate the physicians*
decisions.
(chapter 5.1)
Study objective
Primary 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 objectives:
To evaluate the efficacy of brodalumab compared with guselkumab while on
treatment for up to 28 weeks in adult subjects with moderate to severe plaque
psoriasis and prior inadequate response to ustekinumab.
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.
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.
Study design
This trial is a phase 4, randomised, blinded (subject and assessor),
parallel-group, multi-site, clinical trial. The trial is designed to evaluate
the efficacy and safety of standard administration of brodalumab compared with
standard administration of guselkumab for the treatment of moderate to severe
plaque psoriasis in adult subjects with inadequate response to ustekinumab.
The total duration of the trial will be approximately 32 weeks and includes 3
periods:
• Screening: Week -4/-2 to Week 0.
• Induction: Week 0 to Week 16.
• Maintenance: Week 16 to Week 28.
Screening period (Week -4/-2 to Week 0)
A screening visit will take place a maximum of 4 weeks and minimum of 2 weeks
prior to the treatment period. The objective of the screening period is to
enroll eligible and informed subjects. This entails wash-out of specified
prohibited medication and specified laboratory testing.
Before any trial-related procedure is started, the subjects will receive the
necessary written and verbal information and instructions, including the
written subject information sheet and the informed consent form (ICF). Each
subject will receive a unique subject number and the subject*s eligibility will
be determined by clinical examination and confirmation of the eligibility
criteria.
Induction period (Week 0 to Week 16)
The start of the treatment period is defined as Week 0 (baseline; Day 1). At
this visit, eligibility will be confirmed by re-checking the eligibility
criteria in subjects who were eligible based on previous examinations, review
of sufficient wash-out of prohibited medication, and review of central
laboratory results from the screening visit. If still eligible, the subject
will continue in the trial and be randomised to either brodalumab or guselkumab
treatment regimen as described below.
Arm 1 (brodalumab + dummy 1):
• Brodalumab 210 mg (1.5 ml) subcutaneously at Weeks 0, 1, 2, and then Q2W
until the end of trial (last administration of brodalumab at Week 26).
• Dummy 1 (placebo 1.0 ml) subcutaneously at Weeks 0, 4, and then every 8 weeks
(Q8W) until the end of trial (last administration of dummy 1 at Week 20).
Arm 2 (guselkumab + dummy 2):
• Guselkumab 100 mg (1.0 ml) subcutaneously at Weeks 0, 4, and then Q8W until
the end of trial (last administration of guselkumab at Week 20).
• Dummy 2 (placebo 1.5 ml) subcutaneously at Weeks 0, 1, 2, and then Q2W until
the end of trial (last administration of dummy 2 at Week 26).
The primary endpoint will be assessed at Week 16.
Maintenance period (Week 16 to Week 28)
The subjects will follow the treatment regimen described above. Last injections
(brodalumab in Arm 1 and dummy 2 injection in Arm 2) will be given at Week 26.
The subjects and assessors will be blinded throughout the trial.
Intervention
Kyntheum® (brodalumab)is a recombinant fully human monoclonal immunoglobulin
IgG2-antibody that binds with high affinity to human interleukin (IL)-17
receptor A (IL-17RA), thereby blocking the IL-17 pathway. Brodalumab is
approved in EU, Canada, Japan, Taiwan, Thailand, and the USA for the treatment
of moderate-to-severe plaque psoriasis in adult patients who are candidates for
systemic therapy.
Kyntheum® (brodalumab): Solution for subcutaneous injection, Brodalumab
formulated at a nominal concentration of 140 mg/mL including the
following excipients: Proline, Glutamate, Polysorbate 20, Water for injections
. Pre-filled syringe with 210 mg brodalumab in 1.5 mL solution.
Tremfya® (guselkumab) Guselkumab is a fully human immunoglobulin G1 lambda
(IgG1*) monoclonal antibody to the p19 subunit of IL-23 (IL 23p19).
Tremfya® (guselkumab) Solution for subcutaneous injection, Guselkumab
formulated at a nominal concentration of 100 mg/mL including the following
excipients:
• Histidine
• Histidine monohydrochloride monohydrate
• Polysorbate 80
• Sucrose
Water for injection
Pre-filled syringe with 100 mg guselkumab in 1 ml solution
Placebo; Solution for subcutaneous injection, The placebo solution is similar
to the active brodalumab solution except that it does not contain any active
substance. Pre-filled syringe with 1.0 or 1.5 mL solution.
Study burden and risks
Brodalumab and guselkumab are approved treatments for adult patients with
moderate to severe plaque psoriasis who are candidates for systemic therapy.
Data from this trial will provide more information on the efficacy and safety
of the treatments to support the choice of treatment after inadequate response
to ustekinumab.
The risk to subjects in this trial will be minimised by fulfilment of all
eligibility criteria and by close clinical monitoring. To ensure the safety and
well-being of subjects participating in this trial, there will be ongoing
monitoring of the subjects, reporting of any AEs, and well defined IMP
discontinuation criteria).
The subjects in this trial will be blinded by additional (dummy) injections due
to differences in the volume and administration frequency between brodalumab
and guselkumab. Additional (dummy) injections are not expected to increase the
low risk normally associated with injections. Similarly, the blood sampling
procedure poses the same low risk as normally associated with this procedure.
Altogether, the risks associated with participating in this trial are
considered low and are expected to be outweighed by the benefit of providing
additional information for psoriasis patients and clinicians.
Industriparken 55
Ballerup 2750
DK
Industriparken 55
Ballerup 2750
DK
Listed location countries
Age
Inclusion criteria
- Signed and dated informed consent has been obtained prior to any
protocol-related procedures.
- Age >=18 years of age at the time of screening.
- Diagnosed with plaque psoriasis for at least 6 months before the first
administration of IMP as
determined by the investigator.
- 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.
- Investigator's Global Assessment (IGA) >=2 at screening and baseline.
- Absolute PASI >3 at screening and baseline.
- No current evidence of active tuberculosis test).according to local standard
of care for patients requiring initiation of a biologic treatment..
Exclusion criteria
• 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 the investigational
medicinal product (IMP) on plaque psoriasis.
• Clinically important active infections or infestations, chronic, recurrent or
latent infections or infestations, or is immunocompromised (e.g., human
immunodeficiency virus) or known history of eg hepatitis B, C, HIV
• Any systemic disease (including, but not limited to, renal failure, heart
failure, liver disease, diabetes, and anemia) considered by the investigator to
be clinical significant and uncontrolled and/or placing the subject at undue
risk of intercurrent diseases
• Known history of Crohn*s disease.
• Myocardial infarction or stroke, or unstable angina pectoris within the past
12 months.
• Any active malignancy.
• History of malignancy within 5 years, except for treated and considered cured
cutaneous quamous or basal cell carcinoma, in situ cervical cancer, or in situ
breast ductal carcinoma.
• History of suicidal behavior (i.e., *actual suicide attempt*, *interrupted
attempt*, *aborted attempt*, or *preparatory acts or behavior*) based on the
Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at screening or
at baseline.
• Any suicidal ideation of category 4 or 5 (*active suicidal ideation with some
intent to act, without specific plan* or * active suicidal ideation with
specific plan and intent*) based on the C-SSRS questionnaire at screening or at
baseline.
• A Patient Health Questionnaire (PHQ)-8 score of >=10 corresponding to
moderate-to-severe depression at screening or at baseline.
History of depressive disorder with severe episode(s) within the last 2 years
Known or suspected hypersensitivity to any component(s) of the IMPs.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004099-20-NL |
| ClinicalTrials.gov | NCT04533737 |
| CCMO | NL74156.056.20 |