E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe plaque psoriasis |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071117 |
E.1.2 | Term | Plaque psoriasis |
E.1.2 | System Organ Class | 100000004858 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate efficacy of brodalumab treatment 210 mg every
two weeks (Q2W) in subjects with moderate to severe plaque psoriasis in whom the
treatment response to TNF-alpha inhibitors (standard of care) is insufficient, measured as
proportion of subjects achieving PASI <3 after 12 weeks of treatment (brodalumab arm vs
TNF/brodalumab arm). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the clinical treatment effect of brodalumab treatment 210 mg Q2W in subjects with moderate to severe plaque psoriasis who are insufficient responders to TNF-alpha inhibitor treatment (standard of care) and the subjects’ quality of life, assessed by PASI, DLQI, Montgomery-Åsberg Depression Rating Scale (MADRS), Hospital Anxiety and Depression Scale (HADS), Patient Global Assessment (PaGA) and Visual Analogue Scale (VAS) (pruritus / itch). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed and dated informed consent has been obtained
2) Men or women ≥18 years of age at the time of screening
3) Subjects with moderate to severe plaque psoriasis diagnosed ≥6 months before
randomisation
4) Subjects on TNF-alpha inhibitors, either Adalimumab or Etanercept, for at least 24 weeks (Etanercept) or 16 weeks (Adalimumab), with at time of inclusion an absolute PASI score >7 or PASI 3-7 + DLQI >5 + BSA >3.
5) Subject has no known history of active tuberculosis
6) A female subject of childbearing potential* is eligible to participate if she is not pregnant.
*Female subjects are considered of childbearing potential unless they have undergone
hysterectomy, bilateral salpingectomy or bilateral oophorectomy, or have been post-menopausal for at least one year prior to first visit.
7) Using effective contraceptive measures:
Women of childbearing potential should use an effective method of contraception during
treatment and for at least 12 weeks after treatment.
Male subject with a female partner of childbearing potential who is willing to use effective contraceptive methods*. Male subjects should not donate sperm for at least 12 weeks following last dose of investigational product.
*Effective contraceptive methods as required by local regulation or practice for at least 12 weeks following last dose of investigational product.
8) Subject and/or subject’s designee is/are capable of administering subcutaneous
injections |
|
E.4 | Principal exclusion criteria |
1) Subject has an active infection as follows: any active infection for which systemic anti-infectives were used within 28 days prior to first dose of IMP, a serious infection defined
as requiring hospitalisation or intravenous anti-infectives within 8 weeks prior to the first
dose of IMP, recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject.
2) 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.
3) Subjects with active or known history of inflammatory bowel disease (IBD) including Crohn’s disease.
4) Previous treatment with IL-17 inhibitors (Secukinumab and/or Ixekizumab)
5) Planned surgery, which in the opinion of the investigator would influence planned
treatment with IMP.
6) Subjects with a history of suicidal behaviour.
7) Known or suspected hypersensitivity to any components of the IMP.
8) Current participation in any other interventional clinical study, ending another
interventional clinical study less than 4 weeks prior to screening visit, or receiving other
investigational agents (based on interview of the subject).
9) Subjects who have received treatment with any non-marketed drug substance (i.e. an
agent which has not yet been made available for clinical use following registration) within
the last 4 weeks prior to screening visit.
10) Previously enrolled in this clinical study.
11) In the opinion of the (sub)investigator, the subject is unlikely to comply with the clinical study protocol (e.g. due to alcoholism, drug addiction or psychotic state).
12) Subjects in close affiliation with the study personnel (e.g. immediate family member or subordinate), subjects who are a member of the clinical study personnel, or an employee of the sponsor or a CRO involved in the study.
13) Subjects under guardianship, hospitalised in a public or private institution, for a reason other than research, or subjects deprived of freedom.
14) Female subjects who are pregnant or breastfeeding.
15) Subject has any concurrent medical condition that, in the opinion of the investigator,
could cause this study to be detrimental to the subject. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving PASI <3 after 12 weeks of treatment (brodalumab
arm vs TNF/brodalumab arm) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
PASI at weeks 0,4,8 and 12 for brodalumab arm and at weeks 0,8,12,16,20 and 24 for TNF/brodalumab arm |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints
-The proportion of subjects with ≥75%, ≥90%, 100% improvements in PASI score
(PASI 75, PASI 90, PASI 100) at week 12 (brodalumab arm) and weeks 12 and 24
(TNF/brodalumab arm)
-Change from baseline in PASI score at week 12 (brodalumab arm) and weeks 12 and
24 (TNF/brodalumab arm)
-PASI improvement (%) from baseline at week 12 (brodalumab arm) and weeks 12
and 24 (TNF/brodalumab arm)
-Change from baseline in DLQI total score at week 12 (brodalumab arm) and
weeks 12 and 24 (TNF/brodalumab arm)
-Proportion of subjects with DLQI total score of 0 or 1 at week 12 (brodalumab arm)
and weeks 12 and 24 (TNF/brodalumab arm)
-Change in MADRS at week 12 (brodalumab arm) and weeks 12 and 24
(TNF/brodalumab arm)
-Change in HADS at week 12 (brodalumab arm) and weeks 12 and 24
(TNF/brodalumab arm)
-Change from baseline in PaGA score at week 12 (brodalumab arm) and weeks 12
and 24 (TNF/brodalumab arm)
-PaGA improvement (%) from baseline at week 12 (brodalumab arm) and weeks 12
and 24 (TNF/brodalumab arm)
-Change in VAS pruritus / itch at week 12 (brodalumab arm) and weeks 12 and 24
(TNF/brodalumab arm)
Exploratory Efficacy Endpoints
-Change from baseline (day 0) in serum pro-inflammatory psoriasis cytokines (to be
detailed later) at week 12 (brodalumab arm) and change from baseline (day 0)
compared to weeks 12 and 24 (TNF/brodalumab arm)
-Change from baseline (day 0) in s-calcium, serum vitamin D levels (free and bound
25OHD), and parathyroid hormone (PTH) at week 12 (brodalumab arm) and change
from baseline (day 0) compared to weeks 12 and 24 (TNF/brodalumab arm)
-Changes from baseline (day 0) in gut microbiome and inflammatory markers in serum
and stool samples (serum and faecal calprotectin as well as serum serotonin) at week
12 (brodalumab arm) and change from baseline (day 0) compared to weeks 12 and
24 (TNF/brodalumab arm) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
-PASI, DLQI, MADRS, HADS, PaGA and VAS at weeks 0,4,8 and 12 for brodalumab arm and at weeks 0,8,12,16,20 and 24 for TNF/brodalumab arm.
-s-cytokines, s-calcium, s-vitamin d, parathyroid hormone (PTH), s- and f-calpro and s-serotonin at weeks 0 and 12 for brodalumab arm and at weeks 0,12 and 24 for TNF/brodalumab arm. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |