Clinical trial NCT04237116: A Study of Secukinumab Treatment in Patients With Plaque Psoriasis and Coexisting Non-alcoholic Fatty Liver Disease (NAFLD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Plaque Psoriasis
Non-alcoholic Fatty Liver Disease
Keywords: plaque psoriasis
NAFLD
NASH
PASI
secukinumab
non-alcoholic fatty liver disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-01-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The primary objective of this study was 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.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean and SD Change From Baseline of PASI Score up to Week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Serum Alanine Aminotransferase (ALT) Level
timeFrame: 12 weeks
measure: Mean and SD of DLQI at Week 12
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
Study officials:
References: