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NCT03745586 | SNCTP000003059

Eine Studie zur Beurteilung der Wirksamkeit von Tocilizumab (Actemra) in Kombination mit einer kurzzeitigen Prednison-Verabreichung zur Behandlung von neu diagnostizierter Riesenzellarteriitis.

Data source: BASEC (Imported from 10.12.2019), WHO (Imported from 01.12.2019)
Changed: 03.12.2019
Disease category: Haut- und Bindegewebekrankheiten (nicht Krebs), Arterielle und venöse Erkrankungen, inkl. tiefe Venenthrombose und Lungenembolie

Brief description of trial (Source of data: BASEC)

Die Riesenzellarteriitis (RZA, engl. Giant Cell Arteritis: GCA) ist eine Erkrankung, die durch Wandentzündung mittelgroßer und großer Arterien gekennzeichnet ist und Menschen über 50 Jahre betrifft. Das jährliche Auftreten schwankt zwischen 6 und 32 Fällen pro 100 000 Personen weltweit. Die GCA ist die häufigste Gefässentzündung der älteren Bevölkerung in Europa. Sie kann zu plötzlicher Erblindung oder zur Ruptur der Aorta (Hauptschlagader) mit tödlichem Ausgang führen.
Die Behandlung mit Kortisonpräparaten (=Glucocorticoide GC) verändert die Symptome und den Verlauf der GCA dramatisch und reduziert die Wahrscheinlichkeit von Gefäß-komplikationen. Krankheitsrückfälle treten jedoch häufig auf, wenn die GC-Dosierung reduziert wird. Dies führt zu häufigen Wiederbehandlungen mit hohen GC-Dosen und schweren Nebenwirkungen (z.B. Zuckerkrankheit, Infektionen, erhöhtes Herzgefäss-Risiko, Knochenbrüche, Muskelverlust, grauer und grüner Star, etc).
In zwei Studien wurde kürzlich gezeigt, dass Actemra - ein bekanntes Medikament zur Behandlung der Rheumatoiden Arthritis - die Krankheitsaktivität der GCA kontrolliert. Basierend auf den vorliegenden Daten ist es wahrscheinlich, dass die Dauer der GC-Therapie erheblich verkürzt werden kann, was zu einer Verminderung der Nebenwirkungen der GC und der Risiken der Kombinationsbehandlung führen wird.

Health conditions investigated (Source of data: BASEC)

neu diagnostizierte Riesenzellarteritis

Health conditions (Source of data: WHO)

Giant Cell Arteritis

Rare disease (Source of data: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

Es wird getested ob eine sehr kurze (3 tägige) Behandlung mit Glucocorticoiden in Kombination mit wöchentlichen Verabreichung Actemra reicht, eine Remission zu erzielen und die Remission über 52 Wochen zu halten

Interventions (Source of data: WHO)

Drug: Tocilizumab;Drug: Glucocorticoids

Criteria for participation in trial (Source of data: BASEC)

klinische Diagnose einer Riesenzellarteritis (Arteritis temporalis oder Polymyalgia rheumatica)
Alter >50 Jahre
Entzündung im Blut, gemessen mittels CRP>25mg/L
mikroskopischer Nachweis einer Gefässentzündung und/oder
Nachweis einer Gefässwandentzündung mit Kernspinuntersuchung (MRI)
Einwilligungserklärung unterschrieben

Exclusion criteria (Source of data: BASEC)

Infektionen oder Infektionsneigung
bestehende Riesenzellarteritis seit mehr als 4 Wochen oder Rückfall einer Riesenzellarteritis
Divertikelentzündung im Dickdarm (sogenannte Diverticulitis) mit Komplikationen, d.h. Darmdurchbruch oder Notwendigkeit einer Antibiotikabehandlung
medikamentöse Therapie mit einem anderen biologischen Wirkstoff in den letzten 6 Monaten

Inclusion/Exclusion Criteria (Source of data: WHO)


Inclusion Criteria:

1. Patients with newly onset Giant Cell Arteritis (GCA) with diagnosis of GCA within 4
weeks before screening visit, satisfying ACR criteria and a CRP > 25 mg/L AND biopsy
proven GCA (according to ACR criteria) OR a large vessel vasculitis assessed by MR
Angiography (MRA) or PET/CT (PET).

2. Previous treatment with GC for a maximum of 10 days since diagnosis of GCA at a
maximal dose of 60 mg/day of prednisone or equivalent.

3. Patient's written informed consent.

Exclusion Criteria:

1. Rheumatic diseases (except for CPPD/chondrocalcinosis) other than GCA or polymyalgia
rheumatica (i.e., RA, autoimmune connectivitides, other systemic vasculitides, a.o.)

2. Chronic use of systemic CS with inability, in the opinion of the investigator, to
withdraw CS treatment at day 4 according to protocol

3. Evidence of significant and/or uncontrolled concomitant disease such as, but not
limited to, cardiovascular disease, nervous system, pulmonary, renal, hepatic,
endocrine (in particular diabetes mellitus) or gastrointestinal disorders (including
previous complicated diverticulitis) which, in the investigator's opinion, would
preclude patient participation or impact the benefit-risk ratio

4. Any condition or general state of health which, in the Investigator's opinion, would
preclude participation in the study

5. Actual or recent myocardial infarction (within the last 3 months before screening
visit)

6. Significant cardiac disease (NYHA Class III and IV), known severe chronic obstructive
pulmonary disease (COPD) (FEV1 < 50% predicted or Functional dyspnea > Grade 3 on the
MRC Dyspnea Scale) or other significant pulmonary disease

7. Uncontrolled disease (such as asthma, psoriasis or inflammatory bowel disease) where
flares are commonly treated with oral or injectable corticosteroids

8. Known active infection of any kind, or any major episode of infection requiring
hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or
completion of oral anti-infectives within 2 weeks before screening visit

9. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within
52 weeks before screening visit

10. Any surgical procedure, including bone/joint surgery within 8 weeks prior before
screening visit or planned within the duration of the study

11. History of serious recurrent or chronic infection (for screening for a chest infection
a chest radiograph will be performed at screening if not performed within 12 weeks
before screening visit

12. Lack of peripheral venous access

13. Body weight > 150 kg or BMI > 35

14. Previous treatment with tocilizumab or any other biological agent within last 6 months
before screening visit; Rituximab within 12 months before screening visit

15. Treatment with any investigational agent within 28 days of screening visit or 5
half-lives of the investigational drug (whichever is the longer)

16. History of severe allergic or anaphylactic reaction to any biologic agent or known
hypersensitivity to any component of tocilizumab

17. Receipt of any vaccine within 28 days prior to screening visit (a patient's
vaccination record and need for immunization prior to receiving tocilizumab/placebo
must be carefully investigated)

18. Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology

19. Positive Quantiferon-TB test for latent Tb without subsequent INH prophylaxis

20. Patients with active Tb which had to be treated for Tb within 2 years before the
screening visit

21. Absolute neutrophil count (ANC) < 2.0 x 103/L, white blood cells < 2.5 x 103/L,
platelet count < 100,000/L

22. Hemoglobin < 8.0 g/dL

23. Concentrations of serum IgG and/or IgM below 5.0 mg/mL and 0.40 mg/mL, respectively

24. Serum creatinine > 2.0 mg/dL

25. Alanine aminotransferase (ALT) or aspartate amino-transferase (AST) > 1.5 times the
upper limit of normal (ULN)

26. Total bilirubin > 1.5 times the upper limit of normal (ULN)

27. Triglycerides > 400 mmol/dL (non-fasted) or > 250 mmol/dL (fasted) at screening

28. Premenopausal status and nursing (definition of postmenopausal status: Female
participants who are surgically sterilised / hysterectomised or post-menopausal for
longer than 2 years are not considered as being of child-bearing potential)

29. Technical implants such as cardiac pacemakers (for MR-angiogram)

30. Claustrophobia (for MR-angiogram)

31. Known allergy against the contrast media (Multihance® or Dotarem® as alternative)

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03745586

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03745586

Further information on trial

Date trial registered

06.11.2018

Incorporation of the first participant

01.12.2018

Recruitment status

Recruiting

Academic title (Source of data: WHO)

Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Source of data: WHO)

Phase 1/Phase 2

Primary end point (Source of data: WHO)

Remission

Secundary end point (Source of data: WHO)

Time to first relapse;Remission

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Bern, Italien, Reggio Emilia, Universitätsspital Bern
Universitätsspital Azienda

Countries (Source of data: WHO)

Italy, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Peter Villiger
+41 31 632 8015
peter.villiger@insel.ch

Contact for general information (Source of data: WHO)

Peter Villiger, Prof;Peter M Villiger, Prof
University of Bern
+41 (0)31 632 98 40
peter.villiger@insel.ch

Contact for scientific information (Source of data: WHO)

Peter Villiger, Prof;Peter M Villiger, Prof
University of Bern
+41 (0)31 632 98 40
peter.villiger@insel.ch

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

University Hospital Inselspital, Berne

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2018-00845

Secondary ID (Source of data: WHO)

2018-00845