Clinical trial NCT02474069: Secukinumab Dosage Optimisation in Partial Responders With Moderate to Severe Plaque-type Psoriasis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate to Severe Plaque-type Psoriasis
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-06-17
Enrollment: 772
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With PASI 90 Response at Week 32
timeFrame: at 32 weeks
measure: Number of Participants With PASI 90 Response at Week 32 for PPS
timeFrame: at week 32
Secondary outcomes:
measure: Selection Phase: Number of Participants Achieving (Psoriasis Area and Severity Index Score)PASI 50, 75, 90, 100
timeFrame: at weeks 1, 2, 3, 4, 8, 12 and 16
measure: Comparative Dose Phase: Number of Participants Achieving Psoriasis Area and Severity Index Score (PASI) 90 and 100
timeFrame: at weeks 18, 22, 30, 32
measure: Selection Phase:Summary of PASI Total Score
timeFrame: at weeks 1,2,3,4,8, 12, 16
measure: Comparative Dose Phase: Summary of PASI Total Score
timeFrame: Weeks 18, 22, 26, 30 and 32
measure: Number of Patients Achieving Dermatology Life Quality Index (DLQI) Scores of 0 or 1 by Visits in the CDP
timeFrame: Weeks 4, 16, 18, 22, 26, 30, 32
measure: Number of Patients Achieving DLQI Total Score <= 5 in the CDP
timeFrame: Weeks 4, 16, 18, 22, 26, 30, 32
measure: Selection Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1
timeFrame: Weeks 4, 16
measure: Comparative Dose Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1
timeFrame: Weeks 18, 22, 26, 30, 32
measure: Selection Phase: Summary of IGA Score
timeFrame: Weeks 4, 16
measure: Comparative Dose Phase:Summary of IGA Score
timeFrame: Weeks 18, 22, 26, 30, 32
Other outcomes:
Locations:
city: Bad Bentheim
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Blaubeuren
country: Germany
facility: Novartis Investigative Site
city: Blaustein
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Borna
country: Germany
facility: Novartis Investigative Site
city: Darmstadt
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Duelmen
country: Germany
facility: Novartis Investigative Site
city: Duisburg
country: Germany
facility: Novartis Investigative Site
city: Duren
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Freising
country: Germany
facility: Novartis Investigative Site
city: Friedrichshafen
country: Germany
facility: Novartis Investigative Site
city: Garching
country: Germany
facility: Novartis Investigative Site
city: Germering
country: Germany
facility: Novartis Investigative Site
city: Giessen
country: Germany
facility: Novartis Investigative Site
city: Glückstadt
country: Germany
facility: Novartis Investigative Site
city: Goslar
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Hildesheim
country: Germany
facility: Novartis Investigative Site
city: Ibbenbuehren
country: Germany
facility: Novartis Investigative Site
city: Ibbenbueren
country: Germany
facility: Novartis Investigative Site
city: Itzehoe
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Langenau
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Lingen
country: Germany
facility: Novartis Investigative Site
city: Loehne
country: Germany
facility: Novartis Investigative Site
city: Luedenscheid
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Munchen
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Oberhausen
country: Germany
facility: Novartis Investigative Site
city: Osnabrueck
country: Germany
facility: Novartis Investigative Site
city: Pommelsbrunn
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Quedlinburg
country: Germany
facility: Novartis Investigative Site
city: Remscheid
country: Germany
facility: Novartis Investigative Site
city: Rheinbach
country: Germany
facility: Novartis Investigative Site
city: Schweinfurt
country: Germany
facility: Novartis Investigative Site
city: Soest
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Straubing
country: Germany
facility: Novartis Investigative Site
city: Stuttgart-Weilimdorf
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Weißenfels
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Wolfenbüttel
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
Study officials:
References: