Clinical trial NCT03055494: Study to Explore the Effect of Secukinumab, Compared to Placebo, on Fat Tissue and Skin in Plaque Psoriasis Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Plaque Psoriasis
Keywords: scalp psoriasis
plaque psoriasis
secukinumab
AIN457
biologic
monoclonal antibod
psoriasis
AIN457A
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-02-16
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility 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

Primary outcomes:
measure: Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 12
timeFrame: 12 weeks
measure: Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 52
timeFrame: 52 weeks
measure: Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 52
timeFrame: 52 weeks
measure: Change in Systolic Blood Pressure From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in Diastolic Blood Pressure From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in Body Weight From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in Glucose Level From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in Insulin Level From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in Homeostatic Model Assessment of Insulin Resistance (UNIT) (HOMA-IR) From Baseline to Week 12
timeFrame: baseline, Week 12
measure: Change in Hemoglobin A1c (HbA1c) Test for Diabetes Score From Baseline to Week 12
timeFrame: baseline, week 12
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Ana
country: United States
facility: Novartis Investigative Site
state: California
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: East Windsor
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: West Orange
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Buffalo
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Webster
country: United States
facility: Novartis Investigative Site
state: Texas
city: Murray
country: United States
facility: Novartis Investigative Site
state: Utah
city: Norfolk
country: United States
facility: Novartis Investigative Site
state: Virginia
Study officials:
affiliation: Novartis
name: Study Lead Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: