Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated With Secukinumab (CARIMA)

April 19, 2017 updated by: Novartis Pharmaceuticals

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).

The purpose of this study was 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 were assessed to evaluate the influence of secukinumab on cardiovascular risk. Magnetic resonance imaging (MRI) was performed in a sub-population to assess the treatment effect on arterial vessel wall morphometry in atherosclerosis prone vascular beds.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
151

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Augsburg, Germany, 86179
        • Novartis Investigative Site
      • Berlin, Germany, 10789
        • Novartis Investigative Site
      • Berlin, Germany, 13187
        • Novartis Investigative Site
      • Bielefeld, Germany, 33647
        • Novartis Investigative Site
      • Bochum, Germany, 44791
        • Novartis Investigative Site
      • Bonn, Germany, 53105
        • Novartis Investigative Site
      • Darmstadt, Germany, 64283
        • Novartis Investigative Site
      • Dresden, Germany, 01307
        • Novartis Investigative Site
      • Duisburg, Germany, 47166
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Frankfurt, Germany, 60590
        • Novartis Investigative Site
      • Freiburg, Germany, 79104
        • Novartis Investigative Site
      • Gera, Germany, 07548
        • Novartis Investigative Site
      • Hamburg, Germany, 20354
        • Novartis Investigative Site
      • Heidelberg, Germany, 69120
        • Novartis Investigative Site
      • Homburg, Germany, 66421
        • Novartis Investigative Site
      • Langenau, Germany, 89129
        • Novartis Investigative Site
      • Lubeck, Germany, 23538
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Muenster, Germany, 48149
        • Novartis Investigative Site
      • München, Germany, 81675
        • Novartis Investigative Site
      • Stade, Germany, 21682
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Chronic moderate to severe plaque type psoriasis for at least 6 months prior to randomization with a Psoriasis Area and Severity Index (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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 300 mg secukinumab
300 mg secukinumab every week for 4 weeks followed by 300 mg secukinumab every 4 weeks until week 48 (last injection)
Drug: Secukinumab
300 mg secukinumab
Other Names:
  • AIN457
Drug: Secukinumab
150 mg secukinumab
Other Names:
  • AIN457
Experimental: 150 mg secukinumab
150 mg secukinumab every week for 4 weeks followed by 150 mg secukinumab every 4 weeks until week 48 (last injection)
Drug: Secukinumab
300 mg secukinumab
Other Names:
  • AIN457
Drug: Secukinumab
150 mg secukinumab
Other Names:
  • AIN457
Other: Placebo followed by 300 mg secukinumab
Placebo until week 12 followed by 300 mg secukinumab every week for 4 weeks followed by 300 mg secukinumab every 4 weeks until week 48 (last injection)
Other: Placebo
Placebo followed by 300 mg secukinumab
Other: Placebo
Placebo followed by 150 mg secukinumab
Other: Placebo followed by 150 mg secukinumab
Placebo until week 12 followed by 150 mg secukinumab every week for 4 weeks followed by 150 mg secukinumab every 4 weeks until week 48 (last injection)
Other: Placebo
Placebo followed by 300 mg secukinumab
Other: Placebo
Placebo followed by 150 mg secukinumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Flow Mediated Dilation (FMD) at Week 12 Followed by Secukinumab 300 mg vs Pooled Placebo Treatment
Time Frame: Week 12
Flow Mediated Dilation (FMD) is non-invasive method evaluated by Doppler Ultrasound test, to assess endothelial function. FMD was calculated as the percent maximal deviation from the baseline arterial diameter (D):FMD = 100*[(D maximum - D baseline) / D baseline]. Here, arterial diameter (brachial artery) was measured at rest (1 minute), during inflation of the distal cuff to 100 millimeter of mercury (mmHg) for 4.5 minutes and for 4.5 minutes following deflation.
Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Flow Mediated Dilation (FMD) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
FMD is non-invasive method evaluated by Doppler Ultrasound test, to assess endothelial function. FMD was calculated as the percent maximal deviation from the baseline arterial diameter (D):FMD = 100*[(D maximum - D baseline) / D baseline]. Here, arterial diameter (brachial artery) was measured at rest (1 minute), during inflation of the distal cuff to 100 mmHg for 4.5 minutes and for 4.5 minutes following deflation. A positive change in FMD constitutes an improvement in endothelial function.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Aortic Augmentation Index at Heart Rate of 75 (AIx-75) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Pulse wave analysis was 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. The waveform derivation employs a validated generalized transfer function to convert a brachial waveform to a central waveform and has been shown to produce measurement results corresponding to measurements using intra-arterial pressure catheters. The augmentation index is derived from the waveform by determining the percentage of the central pulse pressure during systole due to wave reflection. AIx was heart-rate corrected to calculate the AIx at a heart rate of 75 bpm, i.e. AIx-75.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Pulse Wave Velocity (PWV) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Regional arterial pulse wave velocity (PWV) was directly related to arterial stiffness and was 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]). The foot of the arterial pulse wave was 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 was the time interval used in the PWV calculation.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Average Wall Area Assessed as a Measure of Total Plaque Burden at Week 12
Time Frame: Baseline, Week 12
Magnetic resonance imaging (MRI) was used to evaluate vessel wall morphometry to determine plaque burden. As a measure of plaque burden, average wall area was computed by subtracting vessel lumen area from total vessel area. Exploratory 3.0 Tesla MRI technique was applied to assess structure and function of the carotid and the aorta. A 2D axial dark blood T1, T2, proton density weighted spin echo based images and time of flight images were acquired from the bilateral carotid arteries as well as the descending aorta.
Baseline, Week 12
Change From Baseline in Average Wall Area Assessed as a Measure of Total Plaque Burden at Week 52
Time Frame: Baseline, Week 52
Magnetic resonance imaging (MRI) was used to evaluate vessel wall morphometry to determine plaque burden. As a measure of plaque burden, average wall area was computed by subtracting vessel lumen area from total vessel area. Exploratory 3.0 Tesla MRI technique was applied to assess structure and function of the carotid and the aorta. A 2D axial dark blood T1, T2, proton density weighted spin echo based images and time of flight images were acquired from the bilateral carotid arteries as well as the descending aorta.
Baseline, Week 52
Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
High sensitivity C-reactive protein (hsCRP), a soluble biomarker of systemic inflammation was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in S-100 Protein B (Total) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
S100 calcium-binding protein B (S100B-protein), a soluble biomarker of systemic inflammation was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Chemokine (C-c Motif) Ligand 5 (CCL5), Monocyte Chemoattractant Protein 1 (MCP-1) and Macrophage Inflammatory Proteins (MIP) 1 Alpha and 1 Beta at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Chemokine (c-c motif) ligand 5 (CCL5), Monocyte chemoattractant protein 1 (MCP-1) and Macrophage inflammatory proteins (MIP) 1 alpha (1A) and 1 beta (1B), soluble biomarkers of systemic inflammation were determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Fasting plasma glucose (FPG), a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Fasting Insulin at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Fasting Insulin, a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Homeostatic Model Assessment (HOMA) Beta-cell Function at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Homeostatic Model Assessment (HOMA) beta-cell function, a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Homeostatic Model Assessment (HOMA) Insulin Resistance at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
HOMA insulin resistance, a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Hemoglobin A1c (Glycated Hemoglobin) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Hemoglobin A1c (glycated hemoglobin), a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Sex Hormone-binding Globulin (SHBG) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Sex hormone-binding globulin (SHBG), a soluble biomarker of Dysglycemia was determined in fasting blood samples to evaluate the effect of secukinumab on Dysglycemia.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Triglycerides, Total Cholesterol, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Apolipoprotein A-1 (ApoA-1) and Apolipoprotein B (ApoB) at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Triglycerides, Total cholesterol, Low density lipoprotein (LDL), High density lipoprotein (HDL), Apolipoprotein A-1 (ApoA-1) and Apolipoprotein B (ApoB), soluble biomarkers of impaired lipid metabolism were determined in fasting blood samples to evaluate the effect of secukinumab on impaired lipid metabolism.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Adiponectin at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Adiponectin, a soluble biomarker of impaired lipid metabolism was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Baseline, Week 4, 12, 24 and 52
Change From Baseline in Leptin at Week 4, 12, 24 and 52
Time Frame: Baseline, Week 4, 12, 24 and 52
Leptin, a soluble biomarker of impaired lipid metabolism was determined in fasting blood samples to evaluate the effect of secukinumab on systemic inflammation.
Baseline, Week 4, 12, 24 and 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 24, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAIN457ADE02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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