A Study of Secukinumab Treatment in Patients With Plaque Psoriasis and Coexisting Non-alcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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The aim of this study is to assess the therapeutic efficacy of secukinumab on the psoriatic skin and to explore the anti-inflammatory (reduction of hepatic inflammation and cell damage), anti-steatotic (reduction of hepatic triglyceride content) and anti-fibrotic (reduction of hepatic fibrosis) effects of secukinumab in patients with psoriasis and coexisting non-alcoholic fatty liver disease (NAFLD).

Official Title
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A Randomized, Double-blind, Multicenter, 24-week Study of Subcutaneous Secukinumab to Assess Anti-interleukin-17A Treatment in Plaque Psoriasis Patients With Coexisting Non-alcoholic Fatty Liver Disease (pINPOINt)

Conditions
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Plaque Psoriasis, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Biological: Investigational Arm - secukinumab
* Biological: Control Arm - placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female patients, 18 years or older Moderate to severe plaque-type psoriasis, candidate for systemic therapy Diagnosis of NAFLD by either ultrasound at Screening or liver histology within 6 months before Baseline BMI > 25 kg/ m 2 ALT 1.2 to 3.0 × ULN MRI confirmed Liver fat ≥ 8% at Screening Exclusion Criteria: Forms of psoriasis other than chronic plaque-type Psoriasis Drug induced psoriasis Pregnant or nursing (lactating) women Women of child bearing potential unless they are using effective methods of contraception Ongoing use of prohibited treatments Previous treatment with biological drug targeting IL-17 or the IL-17 receptor Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to Screening Unstable weight over the last 6 months prior to Screening. Type I diabetes, or uncontrolled diabetes (Type I or Type II) defined as HbAlc ≥ 10% at screening. Evidence of hepatic decompensation or severe liver impairment or cirrhosis History of liver transplantation or planned liver transplant or biliary diversion. Presence or history of other liver disease Current, or history of, significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening Prior or planned bariatric surgery Inability or unwillingness to undergo MRI of the abdomen Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The primary objective of this study is to demonstrate superiority of secukinumab compared to placebo in patients with moderate to severe chronic plaque-type psoriasis and non-alcoholic fatty liver disease (NAFLD) with respect to psoriasis area and severity index (PASI) 90 response at Week 12.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Arm - secukinumab<br>secukinumab 300mg s.c. weekly in first 4 weeks, followed by q4w up to Week 20; and placebo 300mg s.c. at weeks 13, 14 and 15 to maintain the blind | Biological: Investigational Arm - secukinumab<br>* secukinumab 300mg s.c. weekly in first 4 weeks, followed by q4w up to Week 20; and placebo 300mg s.c. at weeks 13, 14 and 15 to maintain the blind<br>* Other names: AIN457;|
| Placebo Comparator: Control Arm - placebo<br>placebo 300 mg s.c. weekly in first 4 weeks, followed by q4w up to Week 8; and secukinumab 300 mg s.c. weekly for 4 weeks starting at Week 12, followed by q4w up to Week 20 | Biological: Control Arm - placebo<br>* placebo 300 mg s.c. weekly in first 4 weeks, followed by q4w up to Week 8; and secukinumab 300 mg s.c. weekly for 4 weeks starting at Week 12, followed by q4w up to Week 20<br>* Other names: AIN457;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving ≥ 90% improvement (reduction) in PASI score compared to Baseline | Psoriasis Area and Severity Index (PASI) 90 response is defined as ≥ 90% improvement (reduction) in PASI score compared to Baseline | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Alanine Aminotransferase (ALT) level | ALT is an enzyme that the liver releases when it becomes inflamed or damaged. ALT level measures liver function Parameter. | 12 weeks | 
| Percentage of patients achieving DLQI 0/1 at week 12 | Dermatology Life Quality Index (DLQI) is calculated by summing the score of each domain resulting in a maximum of 30 and a minimum of 0. The higher the score, the more Quality of Life was impaired. Meaning of DLQI Scores: 0-1 = no effect at all on patient's life, 2-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20= very large effect on patient's life, 21-30 = extremely large effect on patient's life. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plaque psoriasis, NAFLD, NASH, PASI, secukinumab, non-alcoholic fatty liver disease