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Secukinumab Dosage Optimisation in Partial Responders With Moderate to Severe Plaque-type Psoriasis (GAIN)

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ClinicalTrials.gov Identifier: NCT02474069
Recruitment Status : Completed
First Posted : June 17, 2015
Results First Posted : July 4, 2019
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This study is designed to support the optimal use of secukinumab by providing data to refine guidance on dosing flexibility in patients with psoriasis. The purpose of the study is to explore the effects of dosage interval shorteng to achieve PASI 90 at week 32 for patients who had less than almost clear skin at week 16.

Condition or disease Intervention/treatment Phase
Moderate to Severe Plaque-type Psoriasis Drug: Secukinumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 772 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This was a multicenter, double-blind, randomized study in 772 patients with moderate to severe chronic plaque-type psoriasis. Patients were enrolled at 89 study sites in Germany. The study was divided into 3 phases: screening, selection phase (SP), and comparative dosing phase (CDP). In the screening phase, inclusion and exclusion criteria were confirmed. Eligible patients rolled over into a selection phase (SP) where all patients received 300 mg s.c. open-label secukinumab at baseline, Weeks 1, 2, 3, 4, 8, and 12. At Week 16, PASI response was assessed as a basis for further treatment: 300 mg s.c. secukinumab treatment every 4 weeks vesus 300 mg s.c. secukinumab treatment every 2 weeks.

Patients who achieved at least clear or almost clear skin (≥ PASI 90) at Week 16 discontinued the study

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of 16 Weeks Secukinumab Dosage Interval Shortening in Comparison to Continued Standard Treatment (4-weekly 300 mg s.c.) in Patients With Moderate-severe Plaque Type Psoriasis Who Achieved Less Than Almost Clear Skin After 16 Weeks Under the Standard Dose of Secukinumab
Actual Study Start Date : February 8, 2015
Actual Primary Completion Date : September 15, 2016
Actual Study Completion Date : September 15, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis
Drug Information available for: Secukinumab

Arm Intervention/treatment
Active Comparator: Secukinumab Interval Shortening Drug: Secukinumab
Active Comparator: Secukinumab 4-weekly Drug: Secukinumab



Primary Outcome Measures :
  1. Number of Participants With PASI 90 Response at Week 32 [ Time Frame: at 32 weeks ]
    Number of participants with at least 90% improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

  2. Number of Participants With PASI 90 Response at Week 32 for PPS [ Time Frame: at week 32 ]
    Number of participants with at least 90% improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).


Secondary Outcome Measures :
  1. Selection Phase: Number of Participants Achieving (Psoriasis Area and Severity Index Score)PASI 50, 75, 90, 100 [ Time Frame: at weeks 1, 2, 3, 4, 8, 12 and 16 ]
    Number of participants with at least 50, 75, 90 or 100% improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

  2. Comparative Dose Phase: Number of Participants Achieving Psoriasis Area and Severity Index Score (PASI) 90 and 100 [ Time Frame: at weeks 18, 22, 30, 32 ]
    Number of participants with at least 90 or 100% improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

  3. Selection Phase:Summary of PASI Total Score [ Time Frame: at weeks 1,2,3,4,8, 12, 16 ]
    PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

  4. Comparative Dose Phase: Summary of PASI Total Score [ Time Frame: Weeks 18, 22, 26, 30 and 32 ]
    PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

  5. Number of Patients Achieving Dermatology Life Quality Index (DLQI) Scores of 0 or 1 by Visits in the CDP [ Time Frame: Weeks 4, 16, 18, 22, 26, 30, 32 ]

    The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.

    The DLQI was designed to assess health-related quality of life (HRQoL) in adult patients with skin diseases including psoriasis.


  6. Number of Patients Achieving DLQI Total Score <= 5 in the CDP [ Time Frame: Weeks 4, 16, 18, 22, 26, 30, 32 ]
    The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.

  7. Selection Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1 [ Time Frame: Weeks 4, 16 ]
    The IGA scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe.

  8. Comparative Dose Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1 [ Time Frame: Weeks 18, 22, 26, 30, 32 ]
    The IGA scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe.

  9. Selection Phase: Summary of IGA Score [ Time Frame: Weeks 4, 16 ]
    The IGA scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe.

  10. Comparative Dose Phase:Summary of IGA Score [ Time Frame: Weeks 18, 22, 26, 30, 32 ]
    The IGA scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects eligible for inclusion in this study must fulfill all of the following criteria:

  1. Subjects must be able to understand and communicate with the investigator and must give a written, signed and dated informed consent before any study related activity is performed and who are willing and capable to comply with all study procedures.
  2. Men or women at least 18 years of age at time of screening.
  3. Chronic plaque type psoriasis diagnosed for at least 6 months prior to baseline
  4. Moderate to severe plaque type psoriasis at baseline derived from the European consensus (Mrowietz et al., 2011): BSA (Body Surface Area) >10% and PASI>10 and DLQI>10.
  5. Candidates for biologic therapy who failed to respond to, or who had a contraindication to or were intolerant to previous conventional systemic therapies.
  6. According to local guidelines, to exclude chest infection before initiation of a biologic immunomodulating therapy, it is necessary to have obtained an image of the chest (X-ray, computerized tomography or magnetic resonance imaging) within 12 weeks prior to screening and have this evaluated by a qualified physician.

Exclusion Criteria:

  1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttata psoriasis).
  2. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium).
  3. Ongoing use of prohibited psoriasis and non-psoriasis treatments. Washout periods have to be adhered to.
  4. Subjects not willing to limit UV light exposure (e.g., sunbathing and/or the use of tanning devices) during the course of the study.
  5. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  6. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17A or the IL-17A receptor (e.g. brodalumab, ixekizumab).
  7. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
  8. Study personnel or first degree relatives of investigator(s) must not be included in the study.
  9. Women who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index <1**) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche is required with sufficient lead time before inclusion

    *definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post- surgical bilateral oophorectomy with or without hysterectomy

    **examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynakologie und Geburtshilfe:

    • hormonal oral contraception (Combination of estrogen and gestagen, PI=0.1-0.9) hormonal vaginal ring (combination of estrogen and gestagen, PI=0.65 uncorr.; 0.4 corr.)
    • hormonal transdermal patch (combination of estrogen and gestagen, PI= 0.72 uncorr.; 0.9 corr.)
    • Estrogen-free ovulation inhibitors containing desogestrel (PI=0.14)
    • Implanted hormones containing etonogestrel (PI=0-0.08)
    • Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
    • Intra-uterine progestine device (synthetic progestin containing IUDs,PI=0.16)
    • Oral contraceptives without estrogen (e.g. "mini-pills"), nonsynthetic progesterone only IUDs, female condoms, cervical shield, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  10. Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy. Patients with psoriatic arthritis are not excluded.
  11. Underlying condition (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.
  12. Subjects with preexisting or recent-onset central or peripheral nervous system demyelinating disorders at discretion of the investigator.
  13. Significant medical problems, including but not limited to the following: uncontrolled hypertension (≥160 systolic and/or 95 diastolic mmHg), congestive heart failure [New York Heart Association status of class III or IV].
  14. Subjects with a serum creatinine level exceeding 2.0 mg/dl (176.8μmol/l) at screening.
  15. 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.
  16. Active systemic infections during the last two weeks (exception: common cold) prior to screening or any infection that reoccurs on a regular basis.
  17. History of an ongoing, chronic or recurrent infectious disease including recurrent respiratory and/or urinary tract infections or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test at screening. Subjects with a positive or indeterminate QuantiFERON TB-Gold test may participate in the study if further full tuberculosis work up (according to local practice/guidelines) completed at least 12 weeks prior to first study drug administration establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to local country guidelines for at least 4 weeks prior to screening.
  18. Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to screening.
  19. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
  20. Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the subject unsuitable for the trial or puts the subject at increased risk.
  21. Inability or unwillingness to undergo repeated venipuncture (e.g. because of poor tolerability or lack of access to veins).
  22. 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.
  23. History or evidence of ongoing alcohol or drug abuse, within the last six months before screening.
  24. Plans for administration of live vaccines during the study period or 6 weeks prior to screening.

No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible subjects.


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): NCT02474069


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Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02474069     History of Changes
Other Study ID Numbers: CAIN457ADE04
2014-001974-32 ( EudraCT Number )
First Posted: June 17, 2015    Key Record Dates
Results First Posted: July 4, 2019
Last Update Posted: July 4, 2019
Last Verified: April 2019
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


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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 vulgaris
relapsing psoriasis
remitting psoriasis
plaque-type psoriasis
skin condition
skin disease
itching condition
immune-mediated systemic disease
skin lesions, red skin lesions
scaly patches
papules, plaques
itching
auto-immune
plaque
Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs