Study to Explore the Effect of Secukinumab, Compared to Placebo, on Fat Tissue and Skin in Plaque Psoriasis Patients

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03055494

Acronym

ObePso-S

Enrollment

102

Registered

2017-02-16

Start date

2017-04-18

Completion date

2019-02-26

Last updated

2023-03-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Plaque Psoriasis

Keywords

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

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).

Interventions

BIOLOGICALSecukinumab

Secukinumab 300 mg s.c. at randomization, Weeks 1, 2, 3, and 4 was followed by monthly dosing up to Week 48

BIOLOGICALPlacebo

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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/

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Change in Systolic Blood Pressure From Baseline to Week 12	baseline, Week 12	Vital signs: summary statistics for change from baseline to Week 12
Change in Diastolic Blood Pressure From Baseline to Week 12	baseline, Week 12	Vital signs: summary statistics for change from baseline to Week 12
Change in Body Weight From Baseline to Week 12	baseline, Week 12	Vital signs: summary statistics for change from baseline to Week 12
Change in Glucose Level From Baseline to Week 12	baseline, Week 12	Vital signs: summary statistics for change from baseline to Week 12
Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 52	52 weeks	Response in skin histology/K16 expression to treatment (answered no)
Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 12	baseline, Week 12	Vital signs: summary statistics for change from baseline to Week 12
Change in Homeostatic Model Assessment of Insulin Resistance (UNIT) (HOMA-IR) From Baseline to Week 12	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.
Change in Hemoglobin A1c (HbA1c) Test for Diabetes Score From Baseline to Week 12	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.
Change in Insulin Level From Baseline to Week 12	baseline, Week 12	Vital signs: summary statistics for change from baseline to Week 12
Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 52	52 weeks	Psoriasis Area and Severity Index 90

Countries

United States

Participant flow

Recruitment details

A total of 133 patients were screened for the study, with 82 (61.7%) of these completing the screening phase.

Pre-assignment details

This is The Randomized Set; i.e., all randomized participants

Participants by arm

Arm	Count
Secukinumab 300 mg Participants received secukinumab 300 mg s.c. at randomization	54
Placebo Participants received placebo at randomization	28
Total	82

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Lost to Follow-up	6	0
Overall Study	Non-compliance with study treatment	1	0
Overall Study	Physician Decision	2	0
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Placebo	Total	Secukinumab 300 mg
Age, Continuous	50.4 years STANDARD_DEVIATION 13.1	44.5 years STANDARD_DEVIATION 15.04	41.5 years STANDARD_DEVIATION 15.2
Race/Ethnicity, Customized Asian	3 Participants	6 Participants	3 Participants
Race/Ethnicity, Customized Black	4 Participants	8 Participants	4 Participants
Race/Ethnicity, Customized Caucasian	19 Participants	63 Participants	44 Participants
Race/Ethnicity, Customized Native American	1 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized Other	1 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized Unknown	0 Participants	1 Participants	1 Participants
Sex: Female, Male Female	8 Participants	30 Participants	22 Participants
Sex: Female, Male Male	20 Participants	52 Participants	32 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 54	0 / 28
other Total, other adverse events	39 / 54	25 / 28
serious Total, serious adverse events	1 / 54	1 / 28

Outcome results

Primary

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)

Time frame: 12 weeks

Population: Full Analysis Set (FAS) comprised all patients to assigned study medication. Patients inappropriately randomized (eg, IRT was called in error for randomization of a screen failed patient) were excluded from FAS. Following the intent-to-treat principle, patients were analyzed according to the treatment which they were assigned at randomization.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secukinumab 300 mg	Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 12	43 Participants
Placebo	Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 12	1 Participants

95% CI: [63.3, 88.8]95% confidence interval

Primary

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

Time frame: 12 weeks

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Secukinumab 300 mg	Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12	29 Participants
Placebo	Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12	0 Participants

95% CI: [42.3, 69.3]95% confidence interval

Secondary