Moderate-to-severe psoriasis. Vascular and systemic (splenic) inflammation in psoriasis subjects. MedDRA version: 20.0 Level: LLT Classification code 10050576 Term: Psoriasis vulgaris System Organ Class: 100000004858 MedDRA version: 20.0 Level: LLT Classification code 10003605 Term: Atherosclerosis of aorta System Organ Class: 100000004866 MedDRA version: 20.0 Level: LLT Classification code 10041634 Term: Spleen disorder NOS System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Kyntheum
Pharmaceutical Form: Solution for injection in pre-filled injector
INN or Proposed INN: BRODALUMAB
Other descriptive name: Kyntheum
Concentration unit: mg/ml milligram(s)/millilit
Sponsors
Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained from the subject prior to performing any protocol-related procedures. 2. Age 40 and above. 3. Diagnosis of chronic plaque psoriasis confirmed by a dermatologist 4. Psoriasis area severity index (PASI) = 10 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Non-Danish speaking 2. History of inflammatory bowel disease, arthritis (not including psoriatic arthritis), systemic lupus erythematosus, and active inflammatory skin diseases. 3. A history of malignancies within the past five years (excluding localized non-melanoma skin cancer). 4. Topical corticosteroid treatment (class III or stronger) and/or ultraviolet type B phototherapy within 2 weeks prior to randomization 5. Treatment with psoralen plus ultraviolet type A photochemotherapy, methotrexate, cyclosporine, acitretin, or fumaric acid esters within 4 weeks prior to randomization. 6. Treatment with adalimumab, etanercept, infliximab, cosentyx, or ixekizumab within 12 weeks, ustekinumab within 24 weeks, or other immunosuppressive or anti-inflammatory agents within 5 half-lives of the active substance prior to the FDG-PET/CT, respectively. 7. Scheduled surgery during the trial period (expect minor minimally invasive procedures). 8. Systemic infection or fever within 7 days prior to FDG-PET/CT. 9. Severe obesity (> 150 kg due to a PET/CT scanner limitation). 10. Presence of uncontrolled diabetes mellitus (HbA1c > 75 mmol/mol and/or blood sugar > 11.1 mmol/l and/or clinical judgment). 11. History of coagulation defects (clinical judgment). 12. Active or latent tuberculosis requiring treatment. 13. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb. 14. History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications as determined by medical history and/or subject’s verbal report. 15. No history of varicella zoster infection and negative varicella antibody test (until varicella vaccination is completed). 16. History of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator. 17. History of intravenous drug use. 18. History of attempted suicide or is at significant risk of suicide. 19. Major surgery within the past 3 months. 20. Pregnancy or lactation (Women of childbearing potential must use a highly effective* form of birth control (confirmed by the investigator) throughout the trial and until 12 weeks after discontinuation of treatment with brodalumab. 21. Claustrophobia. 22. Reduced renal function (serum creatinine > 200 µmol/L or cr-EDTA clearance < 30 ml/min) 23. Any disorder, including but not limited to, cardiovascular, lung, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could: o Affect the safety of the subject throughout the trial. o Influence the findings of the trial or their interpretations. o Impede the subject’s ability to complete the entire duration of trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the change in aortic wall inflammation from baseline to week 16 in brodalumab treated psoriasis subjects compared to placebo. ;Secondary Objective: To assess the change in splenic inflammation from baseline to week 16 in brodalumab treated psoriasis subjects compared to placebo. To assess the change in aortic wall subsegment inflammation from baseline to week 16 in brodalumab treated psoriasis subjects compared to placebo. To assess whether changes in skin inflammation is associated with changes in aortic wall inflammation and/or changes in splenic inflammation. Additional: To assess the change in subcutaneous adipose tissue inflammation and whether this change is associated with changes in skin inflammation. To assess the change in soluble inflammatory biomarkers. To assess whether the change in aortic wall inflammation and/or splenic inflammation is associated with psoriasis-specific genotypes. To assess the change in gene expression and cytokine expression in paired lesional and non-lesional psoriatic skin. ;Primary end point(s): Change in the average of maximum Target-to-background (TBR) values (MeanTBRmax) of the entire aorta from baseline to week 16 ;Timepoint(s) of evaluation of this end point: week 0 and week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in the spleen-to-liver ratio (SLR) based on splenic and liver mean standardised uptake values (SUVmean) • Change in the average of maximum TBR values (MeanTBRmax) of the ascending, aortic arch, descending, suprarenal, and infrarenal aorta from baseline to week 16 • Association between change in PASI and change in aortic wall MeanTBRmax • Association between change in PASI and change in SLR Additional secondary endpoints: • Change in the average of maximum SUV values (MeanSUVmax) of the abdomial subcutaneous adipose tissue from baseline to week 16 • Association between change in PASI and change in subcutaneous adipose tissue MeanSUVmax. • Changes in acute phase proteins from baseline to week 16 • Correlation between changes in both aortic meanTBRmax and SLR and prescence of HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39 • Changes in gene expression and cytokine expression in skin samples from baseline to week 16 • Correlation with changes in mean aortic TBRmax and SLR. ;Timepoint(s) of evaluation of this end point: week 0 and week 16 | — |
Countries
Denmark
Contacts
Public ContactSecretary M. Larsen
Aarhus University Hospital
Outcome results
None listed