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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 (METABOLYX)

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ClinicalTrials.gov Identifier: NCT03440736
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : October 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

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 or disease Intervention/treatment Phase
Psoriasis Metabolic Syndrome Drug: Secukinumab Behavioral: Life-style intervention Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 760 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study is a randomized, multi-center, open label, parallel group, active comparator-controlled study with a duration of 28 weeks and a 28 week extension phase.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 28, 2018
Estimated Primary Completion Date : September 15, 2020
Estimated Study Completion Date : March 30, 2021


Arm Intervention/treatment
Active Comparator: Secukinumab 300 mg s.c.
Patients in arm A receive therapy with 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)
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)

Experimental: Secukinumab 300 mg s.c. and lifestyle intervention
Arm B: Patients in arm B receive therapy with 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). In addition they participate in a lifestyle intervention program.
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




Primary Outcome Measures :
  1. PASI 90 [ Time Frame: week 28 ]

    To demonstrate that the combination of Secukinumab (300 mg, 4-weekly s.c.) with lifestyle intervention results in higher psoriasis treatment efficacy than Secukinumab alone in psoriasis patients with concomitant metabolic syndrome.

    Percentage of patients achieving PASI90 at week 28 in both randomized treatment arms, Secukinumab alone and Secukinumab combined with lifestyle intervention



Secondary Outcome Measures :
  1. PASI 75 [ Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    PASI75 in both treatment arms at week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28

  2. hsCRP [ Time Frame: weeks 2, 4, 8, 12, 16, 20, 24 and 28 ]
    hsCRP in both treatment arms throughout the duration of the core study

  3. HbA1c [ Time Frame: weeks 8, 16 and 28 ]
    HbA1c in both treatment arms throughout the duration of the core study

  4. Total cholesterol [ Time Frame: weeks 8, 16 and 28 ]
    Total cholesterol in both treatment arms throughout the duration of the core study

  5. Waist circumference [ Time Frame: week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    Waist circumference in both treatment arms throughout the duration of the core study

  6. Systolic and diastolic blood pressure [ Time Frame: week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    Systolic and diastolic blood pressure in both treatment arms throughout the duration of the core study

  7. Absolute DLQI [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Absolute DLQI in both treatment arms throughout the duration of the core study

    DLQI ranges from 0 to 30, with higher scores indicating greater health related quality of life impairment.


  8. PASI 90 [ Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    PASI 90 in both treatment arms at week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28

  9. PASI 100 [ Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    PASI 100 in both treatment arms at week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28

  10. Absolute PASI [ Time Frame: weeks 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    Absolute PASI scores in both treatment arms at week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28

  11. Fructosamine [ Time Frame: weeks 8, 16 and 28 ]
    Fructosamine in both treatment arms throughout the duration of the core study

  12. Fasting plasma glucose [ Time Frame: weeks 8, 16 and 28 ]
    Fasting plasma glucose in both treatment arms throughout the duration of the core study

  13. LDL [ Time Frame: weeks 8, 16 and 28 ]
    LDL in both treatment arms throughout the duration of the core study

  14. HDL [ Time Frame: weeks 8, 16 and 28 ]
    HDL in both treatment arms throughout the duration of the core study

  15. Triglycerides [ Time Frame: weeks 8, 16 and 28 ]
    Triglycerides in both treatment arms throughout the duration of the core study

  16. Relative change of DLQI [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Relative change of DLQI in both treatment arms throughout the duration of the core study.

    DLQI ranges from 0 to 30, with higher scores indicating greater health related quality of life impairment.


  17. Proportion of patients with DLQI 0/1 [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Proportion of patients with DLQI 0/1 in both treatment arms throughout the duration of the core study.

    DLQI ranges from 0 to 30, with higher scores indicating greater health related quality of life impairment.


  18. Absolute WHO-5 [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Absolute WHO-5 in both treatment arms throughout the duration of the core study.

    The 5-tem World Health Organization Well-Being Index (WHO-5) ranges from 0 % indicating the worst to 100 % indicating the best wellbeing.


  19. Relative change in WHO-5 [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Relative change in WHO-5 in both treatment arms throughout the duration of the core study.

    The 5-tem World Health Organization Well-Being Index (WHO-5) ranges from 0 % indicating the worst to 100 % indicating the best wellbeing.


  20. Absolute self-assessed itch [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Absolute self-assessed itch in both treatment arms throughout the duration of the core study

    A self-administered, 11-point numeric rating scale (NRS, 0-10) where 0 represents no itching and 10 represents itching as bad as it could be.


  21. Absolute self-assessed pain [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Absolute self-assessed pain in both treatment arms throughout the duration of the core study

    A self-administered, 11-point numeric rating scale (NRS, 0-10) where 0 represents no pain and 10 represents pain as bad as it could be.


  22. Absolute self-assessed scaling [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Absolute self-assessed scaling in both treatment arms throughout the duration of the core study

    A self-administered, 11-point numeric rating scale (NRS, 0-10) where 0 represents no scaling and 10 represents scaling as bad as it could be.


  23. Relative change in self-assessed itch [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Relative change in self-assessed itch in both treatment arms throughout the duration of the core study.

    A self-administered, 11-point numeric rating scale (NRS, 0-10) where 0 represents no itching and 10 represents itching as bad as it could be.


  24. Relative change in self-assessed pain [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Relative change in self-assessed pain in both treatment arms throughout the duration of the core study.

    A self-administered, 11-point numeric rating scale (NRS, 0-10) where 0 represents no pain and 10 represents pain as bad as it could be.


  25. Relative change in self-assessed scaling [ Time Frame: week 4, 8, 12, 16, 20, 24, 28 ]

    Relative change in self-assessed scaling in both treatment arms throughout the duration of the core study.

    A self-administered, 11-point numeric rating scale (NRS, 0-10) where 0 represents no scaling and 10 represents scaling as bad as it could be.


  26. Body weight [ Time Frame: week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    Body weight in both treatment arms throughout the duration of the core study

  27. BMI [ Time Frame: week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 ]
    BMI in both treatment arms throughout the duration of the core study. Body weight and height will be combined to report BMI in kg/m^2



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Men or women of at least 18 years of age at the time of screening.
  3. Patients must be able to understand and communicate with the investigator and must be willing and able to comply with all study procedures.
  4. 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%
  5. 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].
  6. 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.

  1. Forms of psoriasis other than chronic plaque-type (e.g. pustular, erythrodermic and guttate psoriasis) at screening.
  2. Previous exposure to Secukinumab or any other biologic drug directly targeting IL17A or the IL17A receptor (e.g. Brodalumab, Ixekizumab).
  3. Exposure to anti-TNF treatment during 1 year prior to baseline.
  4. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at screening.
  5. 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.
  6. History of latex hypersensitivity.
  7. Ongoing participation (including safety follow-up period) in other interventional or non-interventional studies in any dermatological indication
  8. 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.
  9. Diagnosis of type 1 diabetes.
  10. 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
  11. 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.
  12. 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.
  13. 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.
  14. Active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis (PsA) that might confound the evaluation of the benefit of Secukinumab therapy.
  15. 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.
  16. 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)
  17. Medical history of myocardial infarction or angina pectoris
  18. 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.
  19. Serum creatinine level exceeding 2.0 mg/dl (176.8 μmol/L) at screening
  20. 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.
  21. 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.
  22. 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.
  23. Past medical history record or current infection with HIV, hepatitis B or hepatitis C prior to baseline (visit 2).
  24. 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).
  25. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins).
  26. History or evidence of ongoing alcohol or drug abuse, within the last six months before baseline (visit 2).
  27. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03440736


Contacts
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

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Sponsors and Collaborators
Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03440736     History of Changes
Other Study ID Numbers: CAIN457ADE08
First Posted: February 21, 2018    Key Record Dates
Last Update Posted: October 9, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Psoriasis
Metabolic syndrome
Diabetes
Obesity
Life-style
Life-style intervention
Secukinumab
CAIN457A
CAIN457ADE08
AIN457A
Skin condition
skin disease
itching condition
psoriasis vulgaris
relapsing/remitting psoriasis
immune-mediated systemic disease
skin lesions
red skin lesions
scaly patches
papules
plaques
itching

Additional relevant MeSH terms:
Syndrome
Psoriasis
Metabolic Syndrome X
Disease
Pathologic Processes
Skin Diseases, Papulosquamous
Skin Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs