Secukinumab Dosage Optimisation in Partial Responders With Moderate to Severe Plaque-type Psoriasis
Condition: Moderate to Severe Plaque-type Psoriasis
MeSH terms: Psoriasis
Intervention: Secukinumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 772.0
Sex: All
Healthy volunteers: No
Keywords: skin condition; skin disease; itching condition; psoriasis vulgaris; relapsing psoriasis; remitting psoriasis; immune-mediated systemic disease; skin lesions, red skin lesions; scaly patches; papules, plaques; itching; auto-immune; plaque-type psoriasis; plaque

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.
    

Eligibility 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.