| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Rheumatoid Arthritis |
| Revmatoidní artritida |
|
| E.1.1.1 | Medical condition in easily understood language |
| Rheumatoid Arthritis |
| Revmatoidní artritida |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| 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 identify a set of clinical and/or biological markers that allows the identification of the optimal biological mode of action for a given patient with rheumatoid arthritis.
Primary endpoint: Absolute change in the Simplified Disease Activity Index (SDAI) after 24 weeks. |
Cílem studie je identifikovat klinické a biologické markery predikce optimální odpovědi na biologickou léčbu u pacientů s revmatoidní artritidou.
Primárním cílem je absolutní změna aktivity RA hodnocená pomocí Simplified Disease Activity Index (SDAI) po 24 týdnech. |
|
| E.2.2 | Secondary objectives of the trial |
- Relative change in the SDAI after 24 weeks in percent.
- Absolute and relative change in the Clinical Disease Activity Index (CDAI) after 24 weeks in percent.
- Absolute and relative change in the Disease Activity Score 28 (DAS28) after 24 weeks in percent.
- Achieving an SDAI or CDAI response (50%, 70%, 85%)
- Achieving a EULAR response
- Achieving an ACR response (20%, 50%, 70%)
- Change in quality of life (EuroQoL-5D, SF-36) and physical function (HAQ)
- Change in fatigue and sleep
- Proportion achieving a low disease activity state (SDAI ≤11) after 24 weeks
- Proportion achieving a remission state (SDAI ≤3.3) after 24 weeks
- Radiographic progression over 6 months / 12 months |
- Relativní změna SDAI po 24 týdnech (%)
- Absolutní a relativní změna Clinical Disease Activity Index (CDAI) po 24 týdnech (%)
- Absolutní a relativní změna Disease Activity Score 28 (DAS28) po 24 týdnech (%)
- Dosažení odpovědi SDAI nebo CDAI (50%, 70%, 85%)
- Dosažení odpovědi podle EULAR
- Dosažení odpovědi podle ACR response (20%, 50%, 70%)
- Změna kvality života (EuroQoL-5D, SF-36) a fyzické funkce (HAQ)
- Změna, resp. zlepšení únavy a spánku
- Proporce pacientů s nízkou aktivitou nemoci (SDAI ≤ 11) po 24 týdnech
- Radiografická progrese po 6 měsících/ 12 měsících |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Men and women, ≥18 and ≤75 years of age, capable of understanding and signing an informed consent.
2) Classifiable RA according to the 2010 ACR/EULAR criteria or 1987 ARA criteria (present or past)
3) Duration of RA ≤3 years
4) Ongoing conventional DMARD therapy with methotrexate (at least 20 mg/week, or lower if not tolerated in higher doses) or leflunomide (≥ 100mg/week), for ≥6 months, or ≥3 months with documented worsening of disease activity.
5) Clinical Disease Activity Index (CDAI)≥15 corresponding to moderate to severe disease activity. |
1) Muži a ženy ≥18 a ≤75 let věku, schopní porozumění a podpisu informovaného souhlasu.
2) RA klasifikovatelná podle kritérií ACR/EULAR 2010 nebo kritérií ARA 1987 (v současnosti nebo v minulosti)
3) Délka trvání RA ≤3 let
4) Pokračující terapie konvenčními DMARDs - methotrexatem (v dávce alespoň 20mg týdně nebo nižší v případě intolerance vyšších dávek) nebo leflunomidem (≥100mg/ týdně) po dobu ≥6 měsíců nebo ≥3 měsíce s dokumentovaným zhoršením aktivity nemoci
5) Clinical Disease Activity Index (CDAI) ≥15, odpovídající střední nebo vysoce závažné aktivitě nemoci |
|
| E.4 | Principal exclusion criteria |
1) Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
2) Tělesná hmotnost nad 100 kg
3) Užívání glukokortikoidů >10 mg prednisonu denně nebo ekvivalentu
4) Předcházející léčba revmatického onemocnění:
a) intramusculární nebo intraartikulární injekce glukokortikoidů v posledním měsíci
b) monoklonální protilátky nebo jejich fragmenty, registrovanými nebo ve fázi klinického
zkoušení
c) jakékoliv léky ve fázi klinického zkoušení během 5 měsíců nebo po dobu 5 poločasů zkoušeného
léku před screeningem, podle toho, co je delší
d) Azathioprin nebo jiné cytotoxické látky
5) Podávání humánního/ myšího rekombinantního produktu nebo známá alergie na myší produkty v anamnéze.
6) Známá pozitivita viru lidské imunodeficience (HIV) nebo pozitivní antigen HBsAg nebo protilátky proti viru hepatitidy C.
7) Hypergamaglobulinémie před screeningem
8) Anamnéza abúzu alkoholu nebo jiných látek v posledních 6 měsících.
9) Současné nebo minulé
a) serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the
previous 3 months.
b) opportunistic infections (eg, herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis,
histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening.
c) a chronic or recurrent infectious disease (eg, chronic renal infection, chronic chest infection,
COPD, sinusitis, recurrent urinary tract infection, open, draining or infected skin wound or ulcer
etc.).
10) Have undergone any joint replacement surgery.
11) Be men and women of childbearing potential without use of adequate birth control measures
(e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide,
implantable or injectable contraceptives or surgical sterilization), and willingness to continue this
precaution for the duration of the study until 6 months after receiving the last medication.
12) Be considered ineligible according to the tuberculosis (TB) eligibility assessment and screening, or
show a positive test for latent Tbc using Quantiferon assay, unless treatment with INH has been installed for at least 2 weeks prior to starting trial drug.
13) Show evidence of malignancy, or lymphoproliferative disease, or any history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
14) Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
15) Be unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
16) Have presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
17) Have a concomitant diagnosis or history of congestive heart failure (NYHA class III or IV) or diverticulitis.
18) Have a known history of a demyelinating disease, such as multiple sclerosis.
19) Be women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion |
1) Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
2) Tělesná hmotnost nad 100 kg
3) Užívání glukokortikoidů >10 mg prednisonu denně nebo ekvivalentu
4) Předcházející léčba revmatického onemocnění:
a) intramusculární nebo intraartikulární injekce glukokortikoidů v posledním měsíci
b) monoklonální protilátky nebo jejich fragmenty, registrovanými nebo ve fázi klinického
zkoušení
c) jakékoliv léky ve fázi klinického zkoušení během 5 měsíců nebo po dobu 5 poločasů zkoušeného
léku před screeningem, podle toho, co je delší
d) Azathioprin nebo jiné cytotoxické látky
5) Podávání humánního/ myšího rekombinantního produktu nebo známá alergie na myší produkty v anamnéze.
6) Známá pozitivita viru lidské imunodeficience (HIV) nebo pozitivní antigen HBsAg nebo protilátky proti viru hepatitidy C.
7) Hypergamaglobulinémie před screeningem
8) Anamnéza abúzu alkoholu nebo jiných látek v posledních 6 měsících.
9) Současné nebo minulé
a) serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the
previous 3 months.
b) opportunistic infections (eg, herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis,
histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening.
c) a chronic or recurrent infectious disease (eg, chronic renal infection, chronic chest infection,
COPD, sinusitis, recurrent urinary tract infection, open, draining or infected skin wound or ulcer
etc.).
10) Have undergone any joint replacement surgery.
11) Be men and women of childbearing potential without use of adequate birth control measures
(e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide,
implantable or injectable contraceptives or surgical sterilization), and willingness to continue this
precaution for the duration of the study until 6 months after receiving the last medication.
12) Be considered ineligible according to the tuberculosis (TB) eligibility assessment and screening, or
show a positive test for latent Tbc using Quantiferon assay, unless treatment with INH has been installed for at least 2 weeks prior to starting trial drug.
13) Show evidence of malignancy, or lymphoproliferative disease, or any history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
14) Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
15) Be unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
16) Have presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
17) Have a concomitant diagnosis or history of congestive heart failure (NYHA class III or IV) or diverticulitis.
18) Have a known history of a demyelinating disease, such as multiple sclerosis.
19) Be women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Absolute change in the Simplified Disease Activity Index (SDAI) after 24 weeks. |
| Absolutní změna Simplified Disease Activity Index (SDAI) po 24 týdnech |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 24 weeks, 48 weeks |
| 24 týdnů, 48 týdnů |
|
| E.5.2 | Secondary end point(s) |
- Relative change in the SDAI after 24 weeks in percent.
- Absolute and relative change in the Clinical Disease Activity Index (CDAI) after 24 weeks in percent.
- Absolute and relative change in the Disease Activity Score 28 (DAS28) after 24 weeks in percent.
- Achieving an SDAI or CDAI response (50%, 70%, 85%)
- Achieving a EULAR response
- Achieving an ACR response (20%, 50%, 70%)
- Change in quality of life (EuroQoL-5D, SF-36) and physical function (HAQ)
- Change in fatigue and sleep
- Proportion achieving a low disease activity state (SDAI ≤11) after 24 weeks
- Proportion achieving a remission state (SDAI ≤3.3) after 24 weeks
- Radiographic progression over 6 months / 12 months |
- Relativní změna SDAI po 24 týdnech (%)
- Absolutní a relativní změna Clinical Disease Activity Index (CDAI) po 24 týdnech (%)
- Absolutní a relativní změna Disease Activity Score 28 (DAS28) po 24 týdnech (%)
- Dosažení odpovědi SDAI nebo CDAI (50%, 70%, 85%)
- Dosažení odpovědi podle EULAR
- Dosažení odpovědi podle ACR response (20%, 50%, 70%)
- Změna kvality života (EuroQoL-5D, SF-36) a fyzické funkce (HAQ)
- Změna, resp. zlepšení únavy a spánku
- Proporce pacientů s nízkou aktivitou nemoci (SDAI ≤ 11) po 24 týdnech
- Proporce pacientů s remisí (SDAI ≤ 3,3) po 24 týdnech
- Radiografická progrese po 6 měsících/ 12 měsících |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 6 months, 12 Months |
| 6 měsíců, 12 měsíců |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Predictive role of biomarkers for the response to the biological treatment with different mode of action |
| Prediktivní úloha biomarkerů pro odpověď na biologickou léčbu s různým mechanismem účinku |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| 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 | No |
| 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 | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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