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

Phase 3TerminatedNCT04237116

Novartis Pharmaceuticals10 enrolled

Overview

The aim of this study was 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).

Primary outcome measure is 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 score compared to Baseline. It is a composite score where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. Score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Primary analysis was planned to be performed comparing treatments with respect to the primary efficacy variable in a logistic regression model. It was planned to present the Odds Ratio and its 95%-confidence interval and p-value. Planned null hypothesis to be rejected was that the Odds Ratio of a PASI90 response for patients with secukinumab vs. patients with placebo is ≥1 after 12 weeks. Due to premature termination and limited number of treated patients with available data (7 in the secukinumab group and 3 in the placebo group), the extent of the originally planned statistical analyses of efficacy data was limited to descriptive summaries (absolute values per visit and changes from baseline; presented as mean and SD) for the score.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Plaque Psoriasis Non-alcoholic Fatty Liver Disease

Interventions

Investigational Arm - secukinumabBIOLOGICAL

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

Control Arm - placeboBIOLOGICAL

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Novartis Investigative Site

Erlangen, Germany

Novartis Investigative Site

Frankfurt, Germany

Novartis Investigative Site

München, Germany

Novartis Investigative Site

Potsdam, Germany

Outcomes

Primary Outcomes

Mean and SD Change From Baseline of PASI Score up to Week 12

Psoriasis Area and Severity Index (PASI) 90 response is defined as ≥ 90% improvement (reduction) in score compared to Baseline. It is a composite score where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. Score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Primary analysis was planned to be performed comparing treatments with respect to the primary efficacy variable in a logistic regression model.

Time frame: 12 weeks

Secondary Outcomes

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. Normal range of values for ALT is about 7 to 56 units per liter (U/L). Higher levels of ALT in the blood indicate more liver problems. Due to the premature study termination and the limited number of treated patients with available data (7 patients in the secukinumab group and 3 patients in the placebo group), the extent of the originally planned statistical analyses of efficacy data was limited to descriptive summaries (absolute values per visit and changes from baseline; presented as mean and standard deviation) for the ALT score.

Time frame: 12 weeks

Mean and SD of DLQI 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. Due to the premature study termination and the limited number of treated patients with available data (7 patients in the secukinumab group and 3 patients in the placebo group), the extent of the originally planned statistical analyses of efficacy data was limited to descriptive summaries (absolute values per visit and changes from baseline; presented as mean and standard deviation) for DLQI scores.

Data from ClinicalTrials.gov

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