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

Moderate to Severe Plaque-type Psoriasis Clinical Trial

— GAIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02474069
• Other study ID #: CAIN457ADE04
• Secondary ID: 2014-001974-32
• Status: Completed
• Phase: Phase 3
• Start date: February 8, 2015
• Est. completion date: September 15, 2016

Study information

• Verified date: April 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 772
• Est. completion date: September 15, 2016
• Est. primary completion date: September 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Moderate to Severe Plaque-type Psoriasis
• Psoriasis

Intervention

Drug:
• Secukinumab

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Blaubeuren
Germany	Novartis Investigative Site	Blaustein
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Borna
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duelmen
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Duren
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Freising
Germany	Novartis Investigative Site	Friedrichshafen
Germany	Novartis Investigative Site	Garching
Germany	Novartis Investigative Site	Germering
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Glückstadt
Germany	Novartis Investigative Site	Goslar
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Hildesheim
Germany	Novartis Investigative Site	Ibbenbuehren
Germany	Novartis Investigative Site	Ibbenbueren
Germany	Novartis Investigative Site	Itzehoe
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Langenau
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lingen
Germany	Novartis Investigative Site	Loehne
Germany	Novartis Investigative Site	Luedenscheid
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Munchen
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Oberhausen
Germany	Novartis Investigative Site	Osnabrueck
Germany	Novartis Investigative Site	Pommelsbrunn
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Quedlinburg
Germany	Novartis Investigative Site	Remscheid
Germany	Novartis Investigative Site	Rheinbach
Germany	Novartis Investigative Site	Schweinfurt
Germany	Novartis Investigative Site	Soest
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Straubing
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Stuttgart-Weilimdorf
Germany	Novartis Investigative Site	Tübingen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Weißenfels
Germany	Novartis Investigative Site	Wiesbaden
Germany	Novartis Investigative Site	Wolfenbüttel
Germany	Novartis Investigative Site	Wuerzburg
Germany	Novartis Investigative Site	Wuppertal
Germany	Novartis Investigative Site	Wuppertal
Germany	Novartis Investigative Site	Wuppertal

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With PASI 90 Response 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).	at 32 weeks
Primary	Number of Participants With PASI 90 Response at Week 32 for PPS	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).	at week 32
Secondary	Selection Phase: Number of Participants Achieving (Psoriasis Area and Severity Index Score)PASI 50, 75, 90, 100	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).	at weeks 1, 2, 3, 4, 8, 12 and 16
Secondary	Comparative Dose Phase: Number of Participants Achieving Psoriasis Area and Severity Index Score (PASI) 90 and 100	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).	at weeks 18, 22, 30, 32
Secondary	Selection Phase:Summary of PASI Total Score	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).	at weeks 1,2,3,4,8, 12, 16
Secondary	Comparative Dose Phase: Summary of PASI Total Score	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).	Weeks 18, 22, 26, 30 and 32
Secondary	Number of Patients Achieving Dermatology Life Quality Index (DLQI) Scores of 0 or 1 by Visits in the CDP	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.	Weeks 4, 16, 18, 22, 26, 30, 32
Secondary	Number of Patients Achieving DLQI Total Score <= 5 in the CDP	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.	Weeks 4, 16, 18, 22, 26, 30, 32
Secondary	Selection Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1	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.	Weeks 4, 16
Secondary	Comparative Dose Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1	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.	Weeks 18, 22, 26, 30, 32
Secondary	Selection Phase: Summary of IGA Score	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.	Weeks 4, 16
Secondary	Comparative Dose Phase:Summary of IGA Score	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.	Weeks 18, 22, 26, 30, 32