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

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)

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).

Study Overview

• Status: Terminated
• Conditions: Plaque Psoriasis; Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Biological: Investigational Arm - secukinumab; Biological: Control Arm - placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Muenchen, Germany, 80377
    • Novartis Investigative Site
  • Potsdam, Germany, 14467
    • Novartis Investigative Site
  • Stuttgart, Germany, 70178
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
• Spain
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Investigational Arm - secukinumab; 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; 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; Other Names: AIN457
Placebo Comparator: Control Arm - placebo; 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; 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; Other Names: AIN457

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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. 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.	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.	12 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Plain Language Trial Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Actual): June 29, 2021
• Study Completion (Actual): July 23, 2021

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: January 20, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: PASI; NAFLD; NASH; non-alcoholic fatty liver disease; plaque psoriasis; secukinumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Skin Diseases, Papulosquamous; Liver Diseases; Fatty Liver; Psoriasis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CAIN457ADE15; 2019-003168-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No