E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
active psoriatic arthritis |
Aktive Schuppenflechtenarthritis |
|
E.1.1.1 | Medical condition in easily understood language |
active psoriatic arthritis |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 |
• To demonstrate non-inferiority of mean values of DAS28 at week 24 of UST monotherapy compared to add-on to MTX with stratification according to patients on or without MTX before randomization. |
|
E.2.2 | Secondary objectives of the trial |
• To demonstrate non-inferiority of mean DAS28 at week 52
Comparative analysis at all visits as illustrated in Flow Chart of
•DAS28 and change in DAS28 incl. DAS28-ESR remission or low disease of UST +/- MTX treatment
•functional outcome (TJC/SJC assessment)
•ACR 20/50/70 response incl. changes in ACR core set (SJC, TJC, HAQ, patient’s and physician’s global assessment, pain, CRP and ESR)
•PASI, BSA and BASDAI
•treatment adherence measured by withdrawal of therapy and drug accountability
•compliance using compliance questionnaire for rheumatology (CQR5)
•quality of life measured by HAQ, EQ5D, DLQI
•functional outcome (Enthesitis (LEI), Dactylitis assessment)
•mtNAPSI
•US assessment (PsASon22) selected sites)
•safety events (frequency and seriousness) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with active psoriatic arthritis who are naïve to UST will be stratified to either without MTX-therapy or on MTX-treatment for at least 12 weeks prior to screening.
Active PsA is defined as
• TJC ≥4 and SJC ≥4 (66/68 joint count) and
• DAS28 ≥ 3,2
• PsA according to CASPAR criteria
• Presence of chest x-ray without signs of active or latent infection (esp. for tuberculosis) within the last 3 months prior to screening
• Permitted pre-treatment of PsA with up to three biologic-agents, whereupon only one biologic agent must be withdrawn due to inadequate response.
• For MTX naïve patients: Previous use of NSAID
• at least age of 18 years
• Written informed consent obtained prior to the initiation of any protocol-required procedures
• Compliance to study procedures and study protocol
Inclusion criteria related to MTX
• For the group on MTX: Patients must have MTX treatment (dosage ≥15mg/week) for at least 12 weeks prior to screening and stable MTX dosages of 15mg once weekly for at least 4 weeks prior to screening
• Compliance of intake of MTX must be documented
• For the group without MTX therapy: patients must be eligible for MTX treatment (according to SmPC) and have not failed prior MTX treatment for the treatment of PsA
|
|
E.4 | Principal exclusion criteria |
• previous use of UST or any other anti-IL23 agent
Exclusion criteria related to IMP
• according to SmPC
• For the group without MTX: Inadequate Response to prior MTX-treatment for Psoriatic Arthritis
Exclusion criteria related to general health:
• previous B-cell depleting therapy
• Patients with other chronic inflammatory articular disease or systemic autoimmune disease with musculoskeletal symptoms
• Patients with active Tb
• Patients with latent Tb, measured by Interferon gamma release assay, that are not pre-treated for at least 1 months and planned to be treated 9 months in total with INH once a day according to local guidelines
• Any active infection, a history of recurrent clinically significant infection, a history of recurrent bacterial infections with encapsulated organisms
• Primary or secondary immunodeficiency
• History of cancer with curative treatment not longer than 5 years ago except basal-cell carcinoma of the skin that had been excised
• Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient's safety and of the study outcome
• History of a severe psychological illness or condition
• Known hypersensitivity to any component of the product
• Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test
• Males or females of reproductive potential not willing to use effective contraception (e.g. contraceptive pill, IUD, physical barrier)
• Alcohol, drug or chemical abuse
Exclusion criteria related to prior treatments:
• Previous DMARD therapy other than MTX at least for the last 28 days prior to screening due to washout time of different DMARD therapies (including Leflunomide etc.)
• Previous immunosuppressive biologic therapy at least for the last 60 days prior to screening due to washout time of different immunosuppressive biologic therapies (including antiTNF etc.)
• current participation in another interventional clinical trial
Exclusion criteria related to laboratory:
• Haemoglobin < 8.5 g / dl
• Neutrophil counts < 1.500 / μl
• Platelet count < 75.000 / μl
• Lower than 1 x 1000 / μl lymphopenia for more than three months prior to inclusion.
• Serum creatinine > 1.4 mg / dl for women or 1.6 mg / dl for men
• AST or ALT > 2.5 time upper limit of norm
Exclusion criteria related to formal aspects:
• Underage or incapable patients
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of mean DAS28 at week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Assessment of mean DAS28 at week 52
Assessment of
- TJC/SJC (66/68)
- ACR response
- Enthesitis (LEI)
- Dactylitis (number and severity of digits involved)
- HAQ
Other efficacy parameters:
- VAS pain
- BASDAI (due to radiological confirmed axial involvement)
- PASI
- mtNAPSI
- DLQI
- EQ5D
- CRQ5 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 52
week 4, 16, 24, 28, 40 and 52 |
|
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 32 |
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 | Yes |
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
|
time point of study closure of all sites |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |