| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Plaque Type Psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objectives of the study are
• to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic treatment-naïve subjects with moderate to severe plaque-type psoriasis
• to assess the safety and tolerability of guselkumab in systemic treatment-naïve subjects with moderate to severe plaque-type psoriasis.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are
- in Study Parts I and II: to compare improvement of health-related quality of life (QOL) and other patient-reported outcomes (PRO) when systemic treatment-naïve subjects with moderate to severe plaque-type psoriasis are treated with guselkumab compared to FAE.
- in Study Part II: to compare sustainability of response to treatment when systemic treatment-naïve subjects with moderate to severe plaque-type psoriasis are treated with guselkumab compared to FAE.
- in Study Part III (guselkumab withdrawal): to investigate the maintenance of response in subjects withdrawn from study treatment, and to explore prediction parameters of disease modification. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female and ≥18 years of age
2. Have a diagnosis of plaque-type psoriasis for at least 6 months before the first administration of study drug
3. Have a PASI >10 or BSA >10 at screening and at baseline
4. Have a DLQI >10 at screening and at baseline
5. Be a candidate for systemic treatment for psoriasis
6. Topical psoriasis therapy is considered to be inadequate by the investigator due to
- inadequate response to, intolerance to or contraindication against topical therapy in the subject’s medical history (documented or reported by the subject)
- and/or disease severity at screening and at baseline
7. Must be eligible for Fumaderm® treatment according to the SmPC
8. Fumaderm® is considered, in the opinion of the investigator, to be an appropriate treatment option
9. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies
10. A woman of childbearing potential must have a negative urine pregnancy test at screening and at Week 0
11. A woman must agree not to donate eggs for the purpose of assisted reproduction during the study and for a period of at least 12 weeks after receiving the last administration of study treatment
12. During the study and for a minimum of 1 spermatogenesis cycle after receiving the last dose of study drug, in addition to the highly effective method of contraception, a man
• who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception during the study and for at least 12 weeks after receiving the last study treatment.
• who is sexually active with a woman who is pregnant must use a condom, during the study and for at least 12 weeks after receiving the last administration of study treatment.
• must agree not to donate sperm during the study and for at least 12 weeks after receiving the last administration of study treatment.
13. Considered eligible according to the following tuberculosis screening criteria
• Have no history of latent or active TB before screening. An exception is made for subjects who have a history of latent TB and are currently receiving treatment for latent TB, will initiate treatment for latent TB before the first administration of study drug, or have documentation of having completed appropriate treatment for latent TB within 5 years before the first administration of study drug. It is the responsibility of the investigator to verify the adequacy of previous anti-tuberculosis treatment and provide appropriate documentation.
• Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination
• Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB before first administration of study drug
• Within 2 months before the first administration of study drug, have a negative QuantiFERON®-TB Gold Plus test result or have a newly identified positive QuantiFERON®-TB Gold Plus test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated before the first administration of study drug.
14. Have a chest radiograph taken within 3 months before the first administration of study drug and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB
15. Agree not to receive a live virus or live bacterial vaccination during the study, or within 3 months after the last administration of study drug; for information on Bacille Calmette-Guérin (BCG) vaccination
16. Agree not to receive a BCG vaccination during the study, or within 12 months after the last administration of study drug
17. Have screening laboratory test results within the following parameters, if one or more of the laboratory parameters is out of range, a single retest of laboratory values is permitted:
• Hematology panel within normal limits
• Serum creatinine ≤1 × upper limit of normal
• Aspartate aminotransferase, alanine aminotransferase, gamma-GT, total bilirubin and alkaline phosphatase levels must be ≤2 × ULN
18. No dipstick detection of proteins or glucose in urine. If there are signs of proteins and/or glucose on urine test strip, the urine sample must be analyzed centrally. Here, protein and glucose levels must not exceed trace levels, eg, </=(+); one re-test (central urine analysis) is allowed.
19. Agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet (UV) light sources during study
20. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol
21. Sign an informed consent form indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. |
|
| E.4 | Principal exclusion criteria |
1. Has received prior systemic treatment of psoriasis including but not limited to
- conventional systemic therapy (eg, methotrexate, cyclosporine, fumaric acid esters and acitretine)
- apremilast and tofacitinib
- drugs targeted for reducing TNF (including but not limited to infliximab, adalimumab or etanercept)
- drugs targeted for reducing IL-12, IL-17, or IL-23 (including but not limited to ustekinumab, tildrakizumab [MK3222], secukinumab [AIN457], ixekizumab [LY2439821], or brodalumab [AMG827])
- alpha-4 integrin antagonists (including but not limited to natalizumab)
2. Has a history or current signs or symptoms of severe, progressive, or uncontrolled liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
3. Has a history of malignancy within 5 years before screening (with the exception of a non-melanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3months before the first study drug administration, or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before first study drug administration)
4. Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal gammopathy of undetermined significance (MGUS); or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly
5. Has a transplanted organ (with exception of a corneal transplant >3 months before the first administration of study drug)
6. Has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced
7. Has or has had a serious infection (eg, sepsis, pneumonia or pyelonephritis), or has been hospitalized or received IV antibiotics for an infection during the 2 months before screening
8. Has or has had herpes zoster within the 2 months before screening
9. Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium)
10. Has a non-plaque form of psoriasis (eg, erythrodermic, guttate, or pustular)
11. Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic non-remitting cystitis), fungal infection (mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers
12. Known allergies, hypersensitivity, or intolerance to guselkumab or its excipients
13. Contraindications to the use of Fumaderm® initial/ Fumaderm® per local prescribing information
14. Has received phototherapy (including, but not limited to, PUVA, narrow-band UVB, balneophototherapy) within 4 weeks of the first administration of study drug
15. Has used topical medications/ treatments that could affect psoriasis (including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, pimecrolimus, tacrolimus, or topical traditional Taiwanese, Korean, or Chinese medicines) within 2 weeks of the first administration of study drug
16. Has received, or is expected to receive, any live virus or bacterial vaccination within 3 months before the first administration of study drug; for BCG vaccine
17. Has had a BCG vaccination within 12 months of screening
18. Has known intolerance or hypersensitivity to any biologic medication, or known allergies or clinically significant reactions to murine, chimeric, or human proteins, mABs, or antibody fragments
19. Has a history of active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening
20. Has a chest radiograph within 3 months before the first administration of study drug that shows an abnormality suggestive of a malignancy or current active infection, including TB
21. Has ever had a non-tuberculous mycobacterial infection or opportunistic infection
22. Has persistently indeterminate (indeterminate on repeat sampling) IGRA, eg, QuantiFERON®-TB Gold Plus test results
23. Is infected with human immunodeficiency virus
24. Tests positive for hepatitis B virus (HBV) infection or seropositive for antibodies to hepatitis C virus (HCV) at screening
25. Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 3 months before the planned first dose of study drug or is currently enrolled in an investigational study
26. Is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 12 weeks after the last dose of study drug
27. Plans to attempt to have a child while enrolled in this study or within 12 weeks after the last dose of study drug |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the proportion of subjects achieving at least a 90% improvement of their psoriasis according to the Psoriasis Area and Severity Index (PASI 90 response) at Week 24. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The major secondary endpoints are:
• The proportion of subjects achieving at least a 75% improvement of their psoriasis according to the PASI (PASI 75 response) at Week 24
• The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24.
Other secondary endpoints are:
• The proportion of subjects achieving a 100% improvement of their psoriasis according to the PASI (PASI 100 response) at Week 24
• The change from baseline in the signs and symptoms aggregate scores of the PSSD at Week 24
• The change from baseline in the individual scale scores for itch, pain and scaling of PSSD components at Week 24
• The proportion of subjects achieving an absolute PASI score ≤1 at Week 24
• The proportion of subjects achieving an IGA score of cleared (0) at Week 24
• The change from baseline of body surface area (BSA) psoriatic involvement at Week 24
• The change from baseline in DLQI score at Week 24
• The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 24 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline
• The change from baseline in the physical and mental component summary scores of SF-36 at Week 24
• Maintenance of response. Proportion of subjects with a
- PASI 75 response at Week 32 who maintain response at Week 56
- PASI 90 response at Week 32 who maintain response at Week 56
- DLQI score 0 or 1 at Week 32 who maintain response at Week 56
- Proportion of subjects with a
- PASI 75 response (compared to baseline) at Week 56
- PASI 90 response (compared to baseline) at Week 56
- PASI 100 response (compared to baseline) at Week 56
- DLQI score 0 or 1 at Week 56
- Proportion of subjects with a
- PASI 75 response (compared to baseline) at Week 32
- PASI 90 response (compared to baseline) at Week 32
- PASI 100 response (compared to baseline) at Week 32
- DLQI score 0 or 1 at Week 32
- Maintenance of response after guselkumab withdrawal. Proportion of subjects of the guselkumab group (GUS-GUS and FAE-GUS) with a
- PASI 90 response at Week 56 who maintain response at Week 100
- Time to loss of response from Week 56 after guselkumab withdrawal at Week 100
• Safety and tolerability data will be summarized using descriptive statistics.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Week 24, Week 32 and Week 56 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Untersucher-verblindet |
| efficacy evaluator blinded |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 38 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
Print
