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

• ClinicalTrials.gov Identifier: NCT03055494
• Recruitment Status: Completed
• First Posted: February 16, 2017
• Results First Posted: March 10, 2020
• Last Update Posted: October 7, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Biological: Secukinumab; Biological: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 18, 2017
• Actual Primary Completion Date: April 25, 2018
• Actual Study Completion Date: February 26, 2019

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 52 [ Time Frame: 52 weeks ]
   Response in skin histology/K16 expression to treatment (answered no)
2. Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 52 [ Time Frame: 52 weeks ]
   Psoriasis Area and Severity Index 90
3. Change in Systolic Blood Pressure From Baseline to Week 12 [ Time Frame: baseline, Week 12 ]
   Vital signs: summary statistics for change from baseline to Week 12
4. Change in Diastolic Blood Pressure From Baseline to Week 12 [ Time Frame: baseline, Week 12 ]
   Vital signs: summary statistics for change from baseline to Week 12
5. Change in Body Weight From Baseline to Week 12 [ Time Frame: baseline, Week 12 ]
   Vital signs: summary statistics for change from baseline to Week 12
6. Change in Glucose Level From Baseline to Week 12 [ Time Frame: baseline, Week 12 ]
   Vital signs: summary statistics for change from baseline to Week 12
7. Change in Insulin Level From Baseline to Week 12 [ Time Frame: baseline, Week 12 ]
   Vital signs: summary statistics for change from baseline to Week 12
8. Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 12 [ Time Frame: baseline, Week 12 ]
   Vital signs: summary statistics for change from baseline to Week 12
9. Change in Homeostatic Model Assessment of Insulin Resistance (UNIT) (HOMA-IR) From Baseline to Week 12 [ Time Frame: baseline, 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.

10. Change in Hemoglobin A1c (HbA1c) Test for Diabetes Score From Baseline to Week 12 [ Time Frame: baseline, 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arkansas

Novartis Investigative Site

Hot Springs, Arkansas, United States, 71913

United States, California

Novartis Investigative Site

Los Angeles, California, United States, 90033

Novartis Investigative Site

Santa Ana, California, United States, 92701

United States, Georgia

Novartis Investigative Site

Atlanta, Georgia, United States, 30342

United States, Indiana

Novartis Investigative Site

Indianapolis, Indiana, United States, 46256

United States, New Jersey

Novartis Investigative Site

East Windsor, New Jersey, United States, 08520

Novartis Investigative Site

West Orange, New Jersey, United States, 07052

United States, New York

Novartis Investigative Site

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

United States, Oregon

Novartis Investigative Site

Portland, Oregon, United States, 97223

United States, Pennsylvania

Novartis Investigative Site

Pittsburgh, Pennsylvania, United States, 15213-3403

United States, Texas

Novartis Investigative Site

Webster, Texas, United States, 77004

United States, Utah

Novartis Investigative Site

Murray, Utah, United States, 84107

United States, Virginia

Novartis Investigative Site

Norfolk, Virginia, United States, 23507

United States, Wisconsin

Novartis Investigative Site

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Study Lead Novartis Pharmaceuticals; Novartis

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] February 23, 2018

Statistical Analysis Plan  [PDF] May 9, 2019

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03055494
• Other Study ID Numbers: CAIN457AUS07
• First Posted: February 16, 2017
• Results First Posted: March 10, 2020
• Last Update Posted: October 7, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

scalp psoriasis; plaque psoriasis; secukinumab; AIN457; biologic; monoclonal antibod; psoriasis; AIN457A

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases