Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated With Secukinumab

Psoriasis Clinical Trial

— CARIMA  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter, Exploratory Evaluation of Surrogate Markers of Cardiovascular Risk in Patients With Active Chronic Plaque-type Psoriasis Treated for up to 52 Weeks With Subcutaneous (s.c.) Secukinumab (300 mg or 150 mg).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02559622
• Other study ID #: CAIN457ADE02
• Status: Completed
• Phase: Phase 3
• First received: August 4, 2015
• Last updated: September 6, 2016
• Start date: April 2014
• Est. completion date: April 2016

Study information

• Verified date: September 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to explore the effect of treatment with 300 mg or with 150 mg secukinumab (administered weekly for 4 weeks followed by four-weekly administration) on endothelial dysfunction and arterial stiffness after 12 weeks and for up to 52 weeks in subjects with chronic plaque-type psoriasis. Furthermore soluble biomarkers will be assessed to evaluate the influence of secukinumab on cardiovascular risk. Magnetic resonance imaging (MRI) will be performed in a subpopulation to assess the treatment effect on arterial vessel wall morphometry in atherosclerosis prone vascular beds.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Chronic moderate to severe plaque type psoriasis for at least 6 months prior to randomization with a PASI score = 10 at randomization.

• Inadequate response, intolerance or contraindication to cyclosporine, methotrexate and psoralen plus ultraviolet A light treatment (PUVA) as documented in the patient's medical history or reported by the patient or determined by the investigator at screening. Relative contraindications such as interference of patient's lifestyle with the treatment are accepted.

Key Exclusion Criteria:

• Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttata psoriasis) at screening or randomization.

• Ongoing use of prohibited psoriasis and non-psoriasis treatments. Washout periods have to be adhered to.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Secukinumab
300 mg secukinumab

Other:
• Placebo
Placebo followed by 300 mg secukinumab
• Placebo
Placebo followed by 150 mg secukinumab

Drug:
• Secukinumab
150 mg secukinumab

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Langenau
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Psoriasis Area and Severity Index	The head, trunk, upper limbs and lower limbs are assessed separately for erythema, thickening (plaque elevation, induration), and scaling (desquamation). The average degree of severity of each sign in each of the four body regions is assigned a score of 0-4. The area covered by lesions on each body region is estimated as a percentage of the total area of that particular body region. Further practical details help the assessment: The PASI score is calculated using the formula: PASI = 0.1(EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL; PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a theoretic maximum of 72.0. The following definition is used in this study: PASI 50 (75, 90, 100): subjects achieving = 50% (75%, 90%, 100%) improvement (reduction) in PASI score compared to baseline (visit 2) are defined having achieved PASI 50 (75, 90, 100).	at weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 52 and for patients entering the extension phase at weeks 60, 68, 76, 84, 92, 100, and 104.	No
Other	Investigators Global Assessment mod 2011	IGA mod 2011 will be conducted for overall psoriatic disease 0: Clear. No signs of psoriasis. Post-inflammatory hyperpigmentation may be present.; Almost clear. Normal to pink coloration of lesions; no thickening; no to minimal focal scaling.; Mild. Pink to light red coloration; just detectable to mild thickening; predominantly fine scaling.; Moderate. Dull bright red, clearly distinguishable erythema; clearly distinguishable to moderate thickening; moderate scaling.; Severe: Bright to deep dark red coloration; severe thickening with hard edges; severe / coarse scaling covering almost all or all lesions.; Based on this scale, a subject will be considered as an IGA 0 or 1 responder if they achieve a score of 0 or 1, respectively and improve by at least 2 points on the IGA scale at a given time point compared to their score at randomization (baseline).	at weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 52 and for patients entering the extension phase at weeks 60, 68, 76, 84, 92, 100, and 104.
Primary	Flow Mediated Dilation	Brachial artery diameter is measured at rest (1 minute), during inflation of the distal cuff to 100 mmHg for 4.5 min and for 4.5 minutes following deflation. FMD is measured as the % maximal increase in diameter following deflation of the cuff.; This is an exploratory, hypothesis-generating study; therefore all endpoints are of non-confirmatory nature. Whether or not Secukinumab has a substantial impact on the cardiovascular system therefore cannot be determined by the primary endpoint alone, but instead will be explored by assessing the complete set of cardiovascular endpoints. No predefined statistical hypothesis will be tested. The justification for this is the difficulty in estimating the effect size due to lack of adequate precedent. For regulatory reasons only, primary and secondary endpoints are identified.	Week 12	No
Secondary	Flow Mediated Dilation	Brachial artery diameter is measured by doppler ultrasound at rest (1 minute), during inflation of a distal cuff to 100 mmHg for 4.5 min and for 4.5 minutes following deflation. FMD is measured as the % maximal increase in diameter following deflation of the cuff.	at weeks 4, 12, 24 and 52
Secondary	Pulse Wave Analysis	Pulse wave analysis is performed on the central aortic pressure waveform as derived by SphygmoCor XCEL from the brachial pressure waveform recorded in a partially-inflated blood pressure cuff around the upper arm.; Parameters determined in pulse wave analysis include central aortic blood pressure (systolic, diastolic, mean, and pulse pressure), augmentation pressure (AP - the added pressure during systole due to wave reflection), and augmentation index (AIx - the percentage of the central pulse pressure due to wave reflection).	at weeks 4, 12, 24 and 52	No
Secondary	Pulse Wave Velocity	Regional arterial pulse wave velocity is directly related to arterial stiffness and is defined as the time it takes for the blood pressure wave to travel from a proximal site to a distal site (relative to the heart) divided by the distance (PWV = ?distance/?time [m/s]). To this end, the foot of the arterial pulse wave is being recorded by using the SphygmoCor XCEL device. XCEL simultaneously measures the pressure waveform at the femoral site (using a partially inflated custom blood pressure cuff) and the carotid site (using hand-held applanation tonometry). The foot-to-foot time between the two pressure waveforms is the time interval used in the PWV calculation.	at weeks 4, 12, 24, and 52	No
Secondary	Biomarkers	Markers of systemic inflammation High sensitivity C-reactive protein (hsCRP) Tumor necrosis factor alpha (TNF alpha) S-100 protein (total) Chemokine (c-c motif) ligand 5 (CCL5) Interferon gamma Interleukins (IL) 1 beta, 2, 4, 5, 6, 8, 9, 10, 12 p70, 13, 17A, and 22 Monocyte chemoattractant protein 1 (MCP-1) Macrophage inflammatory proteins (MIP) 1 alpha, and 1 beta; Markers of dysglycemia Fasting plasma glucose (FPG) Fasting Insulin Homeostatic Model Assessment (HOMA): beta-cell function, insulin resistance Hemoglobin A1c (glycated hemoglobin) Sex hormone-binding globulin (SHBG); Markers of impaired lipid metabolism Triglycerides Total cholesterol Low density lipoprotein (LDL) High density lipoprotein (HDL) Apolipoprotein A-1 (ApoA-1) Apolipoprotein B (ApoB) Adiponectin Leptin	at weeks 4, 12, 24 and 52
Secondary	total plaque burden in the carotid artery and aorta as well as plaque composition in the carotid artery	2D axial dark blood T1, T2, proton density weighted spin echo based images and time of flight images will be acquired from the bilateral carotid arteries as well as the descending aorta. Measures of plaque burden such as wall area, total vessel area, wall thickness and a normalized wall index (NWI) will then be computed. Additionally, and only in the carotids, plaque composition will be evaluated if a subject is found to have a complex atherosclerotic lesion.	at weeks 12 and 52	No