Study to Explore the Effect of Secukinumab, Compared to Placebo, on Fat Tissue and Skin in Plaque Psoriasis Patients (ObePso-S)

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Explore Changes in Subcutaneous Adipose Tissue and Modulation of Skin Inflammation After 12 Weeks of Treatment With Secukinumab, Compared to Placebo, and up to 52 Weeks of Treatment With Secukinumab in Adult Patients With Moderate to Severe Plaque Psoriasis

This study provided a comparison of secukinumab to placebo with respect to skin inflammation as measured by skin exams in comparison to skin biopsies, adipose tissue and blood sample analyses.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Biological: Secukinumab; Biological: Placebo

Detailed Description

This was a randomized, double-blind, placebo-controlled, multicenter design. Patients with moderate to severe plaque psoriasis received secukinumab 300 mg or placebo, with randomization stratified by body weight (< 90 kg, ≥ 90 kg). There were 5 periods to the study: Screening (1 to 4 weeks), Double-blind Treatment Period (12 weeks), Double-blind Induction Period (4 weeks), Open-label Treatment Period (36 weeks), and Follow-up Period (1 week).

During the Double-blind Treatment Period, all patients attended study visits at Baseline, Weeks 1, 2, 3, 4, 8, and 12, and all doses of study treatment were self-administered at the study site. Patients underwent lesional (LS) and non-lesional (NL) skin biopsies at Baseline and Week 12. Assessments for the primary efficacy variable were performed at Week 12 before patients received their Week 12 dose. During the Double-blind Induction Period, patients randomized to placebo were switched to secukinumab 300 mg for the remainder of the study.

K16 and skin histology/biomarkers were assessed from skin biopsies. The Psoriasis Assessment and Severity Index (PASI) and the Investigator's Global Assessment modified 2011 scale (IGA mod 2011) were performed at specified study visits. Safety was monitored by vital signs, weight, waist circumference, body mass index (BMI), and clinical laboratory tests (serum chemistry, hematology, highsensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), homeostatic assessment of insulin resistance (HOMA-IR), viral serology, serum and urine pregnancy).

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90033
      • Novartis Investigative Site
    • Santa Ana, California, United States, 92701
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Novartis Investigative Site
    • West Orange, New Jersey, United States, 07052
      • Novartis Investigative Site
  • New York
    • Buffalo, New York, United States, 14203
      • Novartis Investigative Site
    • New York, New York, United States, 10025 1737
      • Novartis Investigative Site
    • New York, New York, United States, 10065
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97223
      • Novartis Investigative Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-3403
      • Novartis Investigative Site
  • Texas
    • Webster, Texas, United States, 77004
      • Novartis Investigative Site
  • Utah
    • Murray, Utah, United States, 84107
      • Novartis Investigative Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed
• Clinical diagnosis of chronic plaque-type psoriasis at least 6 months prior to randomization

• Moderate to severe plaque psoriasis as defined at baseline by:

  • ≥10% Body Surface Area (BSA) involvement and
  • PASI total score of ≥12 and
  • IGA mod 2011 score of ≥3 (based on a scale of 0-4)

Exclusion Criteria:

• Forms of diagnosed psoriasis other than chronic plaque psoriasis
• Medication-induced or medication exacerbated psoriasis
• Previous exposure to secukinumab or any other biologic drug directly targeting IL-17A or IL-17RA receptors
• Ongoing use of prohibited treatments
• Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Secukinumab; Eligible patients received secukinumab 300 mg s.c. at randomization, Weeks 1, 2, 3 and 4 followed by monthly dosing up to Week 48	Biological: Secukinumab; Secukinumab 300 mg s.c. at randomization, Weeks 1, 2, 3, and 4 was followed by monthly dosing up to Week 48; Other Names: AIN457
Placebo Comparator: Placebo; Eligible patients received placebo at randomization, Weeks 1, 2, 3, 4, and 8. At Week 12, patients were switched to treatment with secukinumab 300 mg s.c. at Weeks 12, 13, 14, 15, and 16 followed by monthly dosing up to Week 48	Biological: Placebo; Placebo s.c. at randomization, Weeks 1, 2, 3, 4, and 8; secukinumab 300 mg s.c. at Weeks 12, 13, 14, 15, and 16 followed by monthly dosing up to Week 48

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 12	Response in skin histology/K16 expression to treatment (answered no)	12 weeks
Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12	Psoriasis Area and Severity Index 90	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 52	Response in skin histology/K16 expression to treatment (answered no)	52 weeks
Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 52	Psoriasis Area and Severity Index 90	52 weeks
Change in Systolic Blood Pressure From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12	baseline, Week 12
Change in Diastolic Blood Pressure From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12	baseline, Week 12
Change in Body Weight From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12	baseline, Week 12
Change in Glucose Level From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12	baseline, Week 12
Change in Insulin Level From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12	baseline, Week 12
Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12	baseline, Week 12
Change in Homeostatic Model Assessment of Insulin Resistance (UNIT) (HOMA-IR) From Baseline to Week 12	Vital signs: summary statistics for change from baseline to Week 12 Healthy Range: 1.0 (0.5-1.4) Less than 1.0 means you are insulin-sensitive which is optimal. Above 1.9 indicates early insulin resistance. Above 2.9 indicates significant insulin resistance.	baseline, Week 12
Change in Hemoglobin A1c (HbA1c) Test for Diabetes Score From Baseline to Week 12	Vital signs: summary statistics for change from baseline to week 12 For people without diabetes, the normal range for the hemoglobin A1c level is between 4% and 5.6%. Hemoglobin A1c levels between 5.7% and 6.4% mean you have a higher chance of getting diabetes. Levels of 6.5% or higher mean you have diabetes.	baseline, week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Actual): April 25, 2018
• Study Completion (Actual): February 26, 2019

Study Registration Dates

• First Submitted: February 14, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 16, 2017

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: psoriasis; AIN457; biologic; plaque psoriasis; secukinumab; scalp psoriasis; AIN457A; monoclonal antibod
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: CAIN457AUS07

Plan for Individual participant data (IPD)

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

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect 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: Yes
• Studies a U.S. FDA-regulated device product: No