Comparison of Secukinumab 300 mg Combined With a Lifestyle Intervention to Secukinumab Alone for the Treatment of Moderate to Severe Psoriasis Patients With Concomitant Metabolic Syndrome

A Randomized, Multicenter 28 Week Study to Compare the Efficacy and Safety of Combining Cosentyx (Secukinumab) (4-weekly, 300 mg s.c.) With a Lifestyle Intervention to Cosentyx Therapy Alone in Adult Patients With Moderate to Severe Plaque-type Psoriasis and Concomitant Metabolic Syndrome, Followed by a 28 Week Extension Period

ClinicalTrials.gov Identifier: NCT03440736

Novartis Reference Number: CAIN457ADE08

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

Around 40% of moderate to severe psoriasis patients are affected by concomitant metabolic syndrome, making it one of the clinically most relevant comorbidities. Psoriasis as well as the metabolic syndrome are both characterized by a state of low-grade systemic inflammation (e.g. in the skin, joints, adipose tissue, liver or vascular endothelium). This shared pathophysiology makes systemic inflammation an attractive target for the treatment of both diseases. Secukinumab as well as lifestyle intervention are able to reduce systemic inflammation.

This trial is designed to answer the question whether the combination of Secukinumab with lifestyle intervention can primarily improve skin symptoms and secondly cardiometabolic status more than Secukinumab alone in psoriasis patients with concomitant metabolic syndrome by targeting the shared pathophysiology behind both diseases, which is systemic inflammation.

Condition 
Psoriasis
Metabolic Syndrome
Phase 
Phase 4
Overall status 
Recruiting
Enrollment count 
760 participants
Start date 
Feb 28, 2018
Completion date 
May 09, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Secukinumab
Secukinumab 300 mg s.c., which consists of two injections with 150 mg prefilled syringes at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 24 (last injection is performed at week 24)
Behavioral
Life-style intervention
A structured program to guide weight loss and increased physical activity

Eligibility Criteria

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed.
Men or women of at least 18 years of age at the time of screening.
Patients must be able to understand and communicate with the investigator and must be willing and able to comply with all study procedures.

Patients with moderate to severe plaque-type psoriasis who are candidates for systemic therapy, diagnosed at least 6 month before randomization and baseline value of

PASI > 10 and
DLQI > 10 and
Body Surface Area (BSA) affected by plaque-type psoriasis ≥ 10%

Fulfillment of Metabolic Syndrome definition (Alberti et al., 2009), which means fulfillment of ≥3 of the following criteria at screening visit:

Fasting (8 hours) plasma glucose ≥ 100 mg/dl or ongoing antidiabetic drug treatment (defined as: metformin, DPP4 inhibitors, GLP1 analogues, SGLT2 inhibitors)
Abdominal obesity defined by elevated waist circumference (measured as defined in section 6.4.5): Male: ≥94 cm, female: ≥80 cm (except for patients of Asian, South or Central American ethnicity, for whom the cut off values are: Male: ≥90 cm, female: ≥80 cm)
Fasting (8 hours) triglycerides ≥ 150 mg/dl or ongoing drug treatment for elevated triglycerides (defined as: fibrates or nicotinic acid).
Fasting (8 hours) HDL-C < 40 mg/dl in men or < 50 mg/dl in women or ongoing drug treatment for reduced HDL-C (defined as: fibrates, nicotinic acid or statins).
Resting blood pressure: Systolic blood pressure ≥ 130 and/ or diastolic blood pressure ≥ 85 mmHg (measured as defined in section 6.4.6) or ongoing antihypertensive drug treatment [defined as: ACE inhibitors, beta blockers, angiotensin receptor antagonists (e.g. Valsartan), aldosterone receptor antagonists, diuretics, nitrates, calcium channel blockers (e.g. Verapamil, Nifedipin), Aliskiren, Clonidin, alpha1 receptor antagonists (e.g. Doxazosin), Dihydralazin, Minoxidil, Moxonidin or Methyldopa].
Willingness and motivation to actively participate in a lifestyle intervention, which means patients need to be willing to increase physical activity and to change dietary habits.

Exclusion Criteria:

Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.

Forms of psoriasis other than chronic plaque-type (e.g. pustular, erythrodermic and guttate psoriasis) at screening.
Previous exposure to Secukinumab or any other biologic drug directly targeting IL17A or the IL17A receptor (e.g. Brodalumab, Ixekizumab).
Exposure to anti-TNF treatment during 1 year prior to baseline.
Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at screening.
History of hypersensitivity to Secukinumab, trehalose-dihydrate, L-histidine, L-histidinhydrochloride-monohydrate, L-methionine, polysorbate 80, water for injection, or to substances of similar chemical classes.
History of latex hypersensitivity.
Ongoing participation (including safety follow-up period) in other interventional or non-interventional studies in any dermatological indication
Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to be adhered to (Table 5-1). Note: Administration of live vaccines 6 weeks prior to baseline (visit 2) or during the study period is also prohibited.
Diagnosis of type 1 diabetes.

Patients with diagnosed type 2 diabetes, if they fulfill one or more of the following conditions:

uncontrolled type 2 diabetes, meaning HbA1c > 8.0%,
pharmacological therapy with one or more of the following agents: Insulin, sulfonylurea agents/analogues, thiazolidinediones/glitazones
Insufficiently controlled, severe arterial hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 95 mmHg) with urgent need for therapy initiation or foreseeable need for medication change during the duration of the core study.
Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
Active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis (PsA) that might confound the evaluation of the benefit of Secukinumab therapy.
Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
Significant, progressive or uncontrolled medical problems at baseline which according to the opinion of the Investigator render the subject unsuitable for the trial - also in regard to participation in the lifestyle intervention - or put the subject at increased risk when participating in the trial (e.g. broken leg, congestive heart failure NYHA III/IV, uncontrolled hypertension with systolic ≥ 160 mmHg and/or diastolic ≥ 95 mmHg, severe uncontrolled asthma)
Medical history of myocardial infarction or angina pectoris
Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
Serum creatinine level exceeding 2.0 mg/dl (176.8 μmol/L) at screening
Total white blood cell (WBC) count < 2,500/μl, or platelets < 100,000/μl or neutrophils < 1,500/μl or hemoglobin < 8.5 g/dl at screening.
Active systemic infections during the last two weeks (exception: common cold) prior to baseline (visit 2) or any infection that reoccurs on a regular basis.
History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test (QFT) at screening. Subjects with a positive or indeterminate QFT test may participate in the study if full tuberculosis work up (according to local practice/guidelines) was completed within 12 weeks prior to visit 2 and establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then appropriate treatment must have been initiated at least 4 weeks prior to baseline (visit 2) and maintained according to local guidelines.
Past medical history record or current infection with HIV, hepatitis B or hepatitis C prior to baseline (visit 2).
History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (except for Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks prior to baseline (visit 2); carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins).
History or evidence of ongoing alcohol or drug abuse, within the last six months before baseline (visit 2).

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of investigational drug for at least 20 weeks after the end of Secukinumab treatment. Basic contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 m prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps).
Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS)
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Study Locations

Germany
Novartis Investigative Site
Withdrawn
Mannheim, 68305
Baden-Wuerttemberg
Germany
Novartis Investigative Site
Recruiting
Regensburg, 93053
Bavaria
Germany
Novartis Investigative Site
Recruiting
Magdeburg, 39120
Sachen Anhalt
Germany
Novartis Investigative Site
Recruiting
Andernach, 56626
-
Germany
Novartis Investigative Site
Recruiting
Augsburg, 86179
-
Germany
Novartis Investigative Site
Recruiting
Bad Soden, 65812
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 10117
-
Germany
Novartis Investigative Site
Completed
Berlin, 10247
-
Germany
Novartis Investigative Site
Completed
Berlin, 10783
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 10789
-
Germany
Novartis Investigative Site
Withdrawn
Berlin, 12459
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13055
-
Germany
Novartis Investigative Site
Completed
Berlin, 13086
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13088
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13125
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13187
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13507
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13597
-
Germany
Novartis Investigative Site
Recruiting
Bielefeld, 33647
-
Germany
Novartis Investigative Site
Recruiting
Bochum, 44791
-
Germany
Novartis Investigative Site
Recruiting
Bochum, 44793
-
Germany
Novartis Investigative Site
Recruiting
Bonn, 53105
-
Germany
Novartis Investigative Site
Recruiting
Bramsche, 49565
-
Germany
Novartis Investigative Site
Recruiting
Braunschweig, 38100
-
Germany
Novartis Investigative Site
Completed
Darmstadt, 64283
-
Germany
Novartis Investigative Site
Recruiting
Darmstadt, 64283
-
Germany
Novartis Investigative Site
Completed
Detmold, 32756
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01097
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
-
Germany
Novartis Investigative Site
Recruiting
Duesseldorf, 40212
-
Germany
Novartis Investigative Site
Recruiting
Duesseldorf, 40225
-
Germany
Novartis Investigative Site
Recruiting
Erlangen, 91054
-
Germany
Novartis Investigative Site
Recruiting
Falkensee, 14612
-
Germany
Novartis Investigative Site
Recruiting
Frankfurt, 60590
-
Germany
Novartis Investigative Site
Recruiting
Freiburg, 79098
-
Germany
Novartis Investigative Site
Recruiting
Friedrichshafen, 88045
-
Germany
Novartis Investigative Site
Recruiting
Gera, 07548
-
Germany
Novartis Investigative Site
Recruiting
Gottingen, 37075
-
Germany
Novartis Investigative Site
Recruiting
Greifswald, 17475
-
Germany
Novartis Investigative Site
Recruiting
Hagen, 58095
-
Germany
Novartis Investigative Site
Recruiting
Halle (Saale), 06108
-
Germany
Novartis Investigative Site
Withdrawn
Hamburg, 20354
-
Germany
Novartis Investigative Site
Recruiting
Hamburg, 22303
-
Germany
Novartis Investigative Site
Recruiting
Hamburg, 22391
-
Germany
Novartis Investigative Site
Recruiting
Hanau, 63450
-
Germany
Novartis Investigative Site
Recruiting
Hannover, 30625
-
Germany
Novartis Investigative Site
Completed
Ibbenbueren, 49477
-
Germany
Novartis Investigative Site
Recruiting
Kiel, 24105
-
Germany
Novartis Investigative Site
Withdrawn
Koeln, 50674
-
Germany
Novartis Investigative Site
Recruiting
Koeln, 50937
-
Germany
Novartis Investigative Site
Recruiting
Langenau, 89129
-
Germany
Novartis Investigative Site
Recruiting
Leipzig, 04103
-
Germany
Novartis Investigative Site
Recruiting
Leipzig, 04105
-
Germany
Novartis Investigative Site
Recruiting
Lingen, 49809
-
Germany
Novartis Investigative Site
Recruiting
Loehne, 32584
-
Germany
Novartis Investigative Site
Recruiting
Luedenscheid, 58515
-
Germany
Novartis Investigative Site
Recruiting
Magdeburg, 39104
-
Germany
Novartis Investigative Site
Completed
Mainz, 55128
-
Germany
Novartis Investigative Site
Recruiting
Mainz, 55131
-
Germany
Novartis Investigative Site
Recruiting
Memmingen, 87700
-
Germany
Novartis Investigative Site
Recruiting
Moenchengladbach, 41061
-
Germany
Novartis Investigative Site
Recruiting
Muenchen, 81377
-
Germany
Novartis Investigative Site
Recruiting
Muenchen, 81675
-
Germany
Novartis Investigative Site
Recruiting
Muenster, 48149
-
Germany
Novartis Investigative Site
Recruiting
München, 80469
-
Germany
Novartis Investigative Site
Withdrawn
Neu-Ulm, 89231
-
Germany
Novartis Investigative Site
Recruiting
Oberhausen, 46147
-
Germany
Novartis Investigative Site
Recruiting
Oldenburg, 26133
-
Germany
Novartis Investigative Site
Recruiting
Osnabrueck, 49074
-
Germany
Novartis Investigative Site
Withdrawn
Osnabrueck, 49078
-
Germany
Novartis Investigative Site
Completed
Plauen, 08529
-
Germany
Novartis Investigative Site
Recruiting
Pommelsbrunn, 91224
-
Germany
Novartis Investigative Site
Recruiting
Potsdam, 14467
-
Germany
Novartis Investigative Site
Recruiting
Quedlinburg, 06484
-
Germany
Novartis Investigative Site
Recruiting
Remscheid, 42897
-
Germany
Novartis Investigative Site
Recruiting
Seligenstadt, 63500
-
Germany
Novartis Investigative Site
Recruiting
Selters, 56242
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Germany
Novartis Investigative Site
Recruiting
Simmern, 55469
-
Germany
Novartis Investigative Site
Recruiting
Soest, 59494
-
Germany
Novartis Investigative Site
Completed
Stade, 21682
-
Germany
Novartis Investigative Site
Recruiting
Stuttgart, 70178
-
Germany
Novartis Investigative Site
Recruiting
Ulm, 89081
-
Germany
Novartis Investigative Site
Recruiting
Vechta, 49377
-
Germany
Novartis Investigative Site
Withdrawn
Wiesbaden, 65199
-
Germany
Novartis Investigative Site
Recruiting
Wuppertal, 42105
-
Germany
Novartis Investigative Site
Recruiting
Wuppertal, 42349
-
Germany

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
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Phone: 
Email: 

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