Effect of Brodalumab Compared to Placebo on Vascular Inflammation in Moderate-to-severe Psoriasis

A randomised, double-blind, placebo-controlled, trial to evaluate the efficacy of brodalumab monotherapy on vascular and systemic inflammation by 18F-FDG-PET/CT in subjects with moderate-to-severe plaque-type psoriasis who are candidates for systemic therapy

Study Overview

• Status: Unknown
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Brodalumab; Drug: Placebos

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anne Bregnhøj, MD, PhD; Phone Number: +45 2183 5720; Email: annebreg@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Anne Bregnhøj, PhD; Email: annebreg@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. PASI ≥ 10

Exclusion Criteria:

1. Non-Danish speaking
2. Known or suspected allergy or reaction to any component of the IMP formulation.
3. History of inflammatory bowel disease, arthritis (not including psoriatic arthritis), systemic lupus erythematosus, and active inflammatory skin diseases.
4. A history of malignancies within the past five years (excluding localized non-melanoma skin cancer).
5. Topical corticosteroid treatment (class III or stronger) and/or ultraviolet type B phototherapy within 2 weeks prior to randomization
6. Treatment with psoralen plus ultraviolet type A photochemotherapy, methotrexate, cyclosporine, acitretin, or fumaric acid esters within 4 weeks prior to randomization.
7. 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.
8. Scheduled surgery during the trial period (expect minor minimally invasive procedures).
9. Systemic infection or fever within 7 days prior to FDG-PET/CT.
10. Severe obesity (> 150 kg due to a PET/CT scanner limitation).
11. Presence of uncontrolled diabetes mellitus (HbA1c > 75 mmol/mol and/or blood sugar > 11.1 mmol/l and/or clinical judgment).
12. History of coagulation defects (clinical judgment).
13. Active or latent tuberculosis requiring treatment.
14. 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.
15. 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.
16. No history of varicella zoster infection and negative varicella antibody test (until varicella vaccination is completed).
17. 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.
18. History of intravenous drug use.
19. History of attempted suicide or is at significant risk of suicide.
20. Major surgery within the past 3 months.
21. 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.
22. Claustrophobia.
23. Reduced renal function (serum creatinine > 200 μmol/L or cr-EDTA clearance < 30 ml/min)

24. 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:

    • Affect the safety of the subject throughout the trial.
    • Influence the findings of the trial or their interpretations.

    • Impede the subject's ability to complete the entire duration of trial.

      • A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year) such as bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), combined (estrogen 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), vasectomised partner (given that the subject is monogamous). The subjects must have used the contraceptive method continuously for at least 1 month prior to the pregnancy test. A female is defined as not being of child bearing potential if she is postmenopausal (at least 12 months with no menses without an alternative medical cause prior to screening), or surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Brodalumab; Subjects will receive 210 mg of Kyntheum administered by subcutaneous injection at Weeks 0, 1 and 2 followed by 210 mg every other week (EOW) thereafter.	Drug: Brodalumab; Subjects with moderate-to-severe psoriasis are enrolled consecutively and randomly assigned to either active treatment with brodalumab or placebo during the treatment period; Other Names: Kyntheum
Placebo Comparator: Placebo; Subjects will receive placebo doses administered by subcutaneous injection at Weeks 0, 1 and 2 followed by placebo EOW thereafter.	Drug: Placebos; Subjects with moderate-to-severe psoriasis are enrolled consecutively and randomly assigned to either active treatment with brodalumab or placebo during the treatment period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The aortic wall inflammation at baseline and at week 16 in brodalumab treated psoriasis subjects compared to placebo.	The average of maximum TBR values (MeanTBRmax) of the entire aorta at baseline and at week 16	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The splenic inflammation at baseline and at week 16 in brodalumab treated psoriasis subjects compared to placebo.	The spleen-to-liver ratio (SLR) based on splenic and liver mean standardised uptake values (SUVmean)	16 weeks
The aortic wall subsegment inflammation at baseline and at week 16 in brodalumab treated psoriasis subjects compared to placebo.	The average of maximum TBR values (MeanTBRmax) of the ascending, aortic arch, descending, suprarenal, and infrarenal aorta at baseline and at week 16	16 weeks
The skin inflammation at baseline and at week 16 in brodalumab treated psoriasis subjects compared to placebo.	Severity of psoriasis measured by PASI score at baseline and at week 16	16 weeks

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: LEO Pharma

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2018
• Primary Completion (Anticipated): March 15, 2020
• Study Completion (Anticipated): March 15, 2020

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Skin Diseases, Papulosquamous; Inflammation; Psoriasis; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: PsoPET2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No