Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
88
Countries
1
Sites
6
Giant cell arteritis
To compare the effectiveness of treatment with etanercept (ETN) versus methotrexate (MTX) in the induction of sustained steroid-free remission in patients with giant cell arteritis (GCA).
Key facts
- Sponsor
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 12 Mar 2025 → ongoing
- Decision date (initial)
- 2024-05-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Agencja Badań Medycznych
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To compare the effectiveness of treatment with etanercept (ETN) versus methotrexate (MTX) in the induction of sustained steroid-free remission in patients with giant cell arteritis (GCA).
Secondary objectives 8
- To compare the effectiveness of treatment with ETN versus MTX in the prevention of deaths in the course of GCA.
- To compare the effectiveness of treatment with ETN versus MTX in the prevention of severe ischemic complications of GCA.
- To compare the effectiveness of treatment with ETN versus MTX in the maintenance of steroid-free remission in patients with GCA.
- To compare the effectiveness of treatment with ETN versus MTX in the induction of GCA remission.
- To assess the steroid-sparing effect of ETN versus MTX in patients with GCA.
- To compare the effectiveness of treatment with ETN versus MTX in the prevention of GCA relapses
- To assess the influence of treatment with ETN versus MTX on the quality of life of GCA patients
- To compare safety of treatment with ETN versus MTX in patients with GCA.
Conditions and MedDRA coding
Giant cell arteritis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10018250 | Giant cell arteritis | 10047065 |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-506623-29-00 | A randomized trial comparing efficacy and safety of etanercept and methotrexate in giant cell arteritis (EFFECTA) | Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Patient’s written informed consent to participate in the study
- Age ≥ 50 years.
- Diagnosis of GCA according to 2022 American College of Rheumatology/EULAR classification criteria for GCA or, in the case of involvement of only extracranial arteries, patients with a diagnosis of GCA based on medium or large-sized arterities that occurred at the age of ≥ 50 years and was confirmed by imaging, i.e. ultrasound, CT, MRI, conventional angiography or PET-CT, at the time of screening or in the past.
- New onset, refractory or relapsing GCA.
- Active GCA, defined as the presence of symptoms or signs attributed to GCA and not related to prior damage and elevated inflammatory markers, i.e. ESR ≥ 30 mm/1 hour or CRP ≥ 10 mg/L attributed to active GCA at screening or within 8 weeks prior to screening.
- Women of child-bearing potential and men who are sexually active with a woman of child-bearing potential must agree to the use of contraception with an adequate level of effectiveness during treatment with methotrexate/etanercept and for at least 6 months after its completion.
Exclusion criteria 24
- Presence of ischemia of organ important for the patient’s survival (e.g. central nervous system, heart, lungs, kidneys, alimentary tract) in the course of GCA.
- Presence or history of other chronic autoimmune rheumatic disease that could interfere with the evaluation of the results of the following study, including: systemic lupus erythematosus, rheumatoid arthritis, or other systemic connective tissue disease, other than GCA systemic vasculitis.
- Oral mucous ulcers.
- Active stomach or duodenal ulcer.
- Presence or history of demyelinating syndrome
- History of major organ transplant (kidneys, lungs, heart, liver).
- Major surgery within 3 months prior to screening or major surgery planned during the study period.
- Hypersensitivity to methotrexate, etanercept or any other excipients of the methotrexate or etanercept.
- Acute, recurrent or chronic infection (e.g. tuberculosis, HIV infection) for which, in the Investigator’s opinion, participating in the study would expose patient to an unacceptable risk.
- Moderate or severe heart failure (New York Heart Association class III or IV), unstable ischemic heart disease, a stroke or myocardial infarction within 6 months prior to screening, or other cardiovascular disease that, in the Investigator’s opinion, would expose the patient to an unacceptable risk in case of participation in the study.
- Severe liver dysfunction
- Severe renal impairment
- Bone marrow hypoplasia
- Other severe disease (including, but not limited to, respiratory, nervous, endocrine, digestive, urinary tract disease) for which, in the Investigator’s opinion, participating in the study would expose patient to an unacceptable risk.
- A malignancy within 5 years prior to screening, except for: a. A completely resected cervical carcinoma in situ with no signs of recurrence within 12 months prior to screening; b. A completely cured basal cell skin carcinoma with no signs of recurrence within 12 months prior to screening.
- The following abnormalities in laboratory tests at screening: a. WBC < 3 G/L; b. NEU < 1 G/L; c. HGB < 9 g/dL; d. PLT < 100 G/L; e. ALT > 2 x ULN; f. AST > 2 x ULN; g. Total bilirubin >1,5 x ULN; h. eGFR < 50ml/min/1,73 m2; i. positive HBsAg; j. positive anti-HBc (total); k. positive anti-HCV; l. positive anti-HIV; m. positive or equivocal Quantiferon-TB Gold test.
- Positive result of a pregnancy test performed in women of child-bearing potential at screening or Visit 1.
- Previous use of the following treatment: a. Within 2 weeks prior to randomization: oral corticosteroids (CS) >60 mg/day prednisone or equivalent, parenteral CS; b. Within 12 weeks prior to randomization: methotrexate, leflunomide, sulfasalazine, chloroquine, hydroxychloroquine, azathioprine, cyclosporine A, mycophenolate mofetil, TNFα inhibitors, anakinra, abatacept, IL-17 blockers; c. Within 6 months prior to randomization: immunoglobulins, plasmapheresis, cyclophosphamide or other alkylating agents; d. Within 12 months prior to randomization: anti-CD20 antibodies; e. Oral or parenteral CS used chronically for reasons other than GCA.
- Abuse or addiction to drugs, alcohol or psychoactive substances.
- Live/attenuated vaccinations within 3 months prior to screening or planned administration of live vaccination during the study period.
- Use of other investigational drugs within 12 weeks or 5 half-lives, whichever is longer, prior to screening.
- Pregnancy or planned pregnancy during the study.
- Breastfeeding or planned breastfeeding during the study.
- Lack of patient cooperation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Percentage of sustained steroid-free GCA remission at week 52 from randomization, defined as lack of symptoms and signs attributable to GCA and not related to prior damage and normalization of inflammatory markers (i.e. ESR < 30 mm/1 hour and CRP < 10 mg/L) with adherence to the protocol-defined prednisone taper regimen.
Secondary endpoints 13
- Mortality rate in the course of GCA at 52 and 104 week from randomization.
- Percentage of severe ischemic complications of GCA at 52 and 104 week, defined as: a. stroke, b. myocardial infarction, c. complete or partial vision loss, d. limb ischemia, e. ischemia of organs important for the patient's survival (i.e. lungs, kidneys, alimentary tract).
- Percentage of sustained steroid-free GCA remission at week 104 from randomization, defined as lack of symptoms and signs attributable to GCA and not related to prior damage and normalization of inflammatory markers (ESR < 30 mm/1 hour and CRP < 10 mg/L) with adherence to the protocol-defined prednisone taper regimen.
- Percentage of GCA remission at 24, 52, 78 and 104 week from randomization, defined as lack of symptoms and signs attributable to GCA and not related to prior damage and normalization of inflammatory markers (i.e. ESR < 30 mm/1 hour and CRP < 10 mg/L).
- Percentage of GCA remission (defined as lack of symptoms and signs attributable to GCA and not related to prior damage and normalization of inflammatory markers, i.e. ESR < 30 mm/1 hour and CRP < 10 mg/L) with concomitant achievement of prednisone dose ≤ 5mg/day at 26, 52, 78 and 104 week from randomization.
- Percentage of GCA remission (defined as lack of symptoms and signs attributable to GCA and not related to prior damage and normalization of inflammatory markers, i.e. ESR < 30 mm/1 hour and CRP < 10 mg/L) with concomitant achievement of prednisone dose ≤ 7,5mg/day at 26, 52, 78 and 104 week from randomization.
- Cumulative dose of prednisone at 26, 52, 78 and 104 week from randomization.
- Time to GCA relapse (after achieving remission).
- Major GCA relapse within 26, 52, 78 and 104 weeks from randomization.
- Minor GCA relapse within 26, 52, 78 and 104 weeks from randomization.
- Change in quality of life measured by SF-36 v.2 questionnaire at 26, 52, 78 and 104 week (compared to the randomization visit).
- Occurrence of serious adverse events within 26, 52, 78 and 104 weeks from randomization.
- Occurrence of non-serious adverse events within 26, 52, 78 and 104 weeks from randomization.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 5
SUB01984MIG · Substance
- Active substance
- Etanercept
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 3900 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
Comparator 4
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 1930 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- off-label use
Auxiliary 8
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 48 mg milligram(s)
- Max total dose
- 2106 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 48 mg milligram(s)
- Max total dose
- 2106 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10020MIG · Substance
- Active substance
- Prednisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 2632 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10020MIG · Substance
- Active substance
- Prednisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 2632 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10020MIG · Substance
- Active substance
- Prednisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 2632 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10020MIG · Substance
- Active substance
- Prednisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 2632 mg milligram(s)
- Max treatment duration
- 26 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07774MIG · Substance
- Active substance
- Folic Acid
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 15 mg milligram(s)
- Max total dose
- 1170 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07774MIG · Substance
- Active substance
- Folic Acid
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 15 mg milligram(s)
- Max total dose
- 1170 mg milligram(s)
- Max treatment duration
- 78 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
- Sponsor organisation
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
- Address
- Ulica Szaserow 128
- City
- Warsaw
- Postcode
- 04-141
- Country
- Poland
Scientific contact point
- Organisation
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
- Contact name
- Centrum Wsparcia Badań Klinicznych
Public contact point
- Organisation
- Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
- Contact name
- Centrum Wsparcia Badań Klinicznych
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Poland | Ongoing, recruiting | 88 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji
Klinika Reumatologii, Chorób Tkanki Łącznej i Chorób Rzadkich, Ul. Woloska 137, 02-507, Warsaw
Samodzielny Publiczny Szpital Kliniczny Nr 1 Im Prof. Tadeusza Sokolowskiego Pomorskiego Uniwersytetu Medycznego W Szczecinie
Klinika Reumatologii, Chorób Wewnętrznych, Geriatrii i Immunologii Klinicznej, Ul. Unii Lubelskiej 1, 71-252, Szczecin
Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
Centrum Wsparcia Badań Klinicznych, Ulica Szaserow 128, 04-141, Warsaw
Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher
Centrum Wsparcia Badań Klinicznych, Ul. Spartanska 1, 02-637, Warsaw
Szpital Specjalistyczny Im.J.Dietla W Krakowie
Klinika Reumatologii i Immunologii, Ul. Skarbowa 4, 31-121, Cracow
Dolnoslaski Szpital Specjalistyczny Im. T.Marciniaka-Centrum Medycyny Ratunkowej
Klinika Reumatologii i Chorób Wewnętrnych, Ul Gen Augusta Emila Fieldorfa 2, 54-049, Wroclaw
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Poland | 2025-03-12 | 2025-03-12 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 21 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol EU CT 2023-506623-29_for publication | 4.0 |
| Protocol (for publication) | D1_Protocol EU CT 2023-506623-29_track_for publication | 5.0 |
| Protocol (for publication) | D1_Protocol EU CT 2023-506623-29-00 for publication | 5.0 |
| Protocol (for publication) | D4_ Patient facingdocuments_Dzienniczek leku_EFFECTA | 1 |
| Protocol (for publication) | D4_ Patient facingdocuments_Karta Indentyfikacyjna Pacjenta | 2.0 |
| Protocol (for publication) | D4_ Patient facingdocuments_Karta Indentyfikacyjna Pacjenta_track | 2.0 |
| Protocol (for publication) | D4_ Patient facingdocuments_kwestionariusz SF-36v2 for publication | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements_Procedura swiadomej zgody | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material_Ogoszenie o badaniu | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_track | 5.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material_Formularz zgody na obserwacje przebiegu ciazy | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material_Formularz zgody na obserwacje przebiegu ciazy_track | 2.0 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material_ICF do przyszych celow naukowych_ABM | 1 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material_Zgoda na biobankowanie i opcjonalne badania genetyczne | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_etanerceptum | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_methotrexatum | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_methotrexatum | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EU CT 2023-506623-29_for publication | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EU CT 2023-506623-29_track_for publication | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis EU CT 2023-506623-29-00 for publication | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-05 | Poland | Acceptable 2024-05-17
|
2024-05-21 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-06-26 | Poland | Acceptable 2024-05-17
|
2025-06-26 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-10-09 | Poland | Acceptable | 2025-11-17 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-12-22 | Poland | Acceptable 2026-02-22
|
2026-02-24 |