A study to assess the effectiveness of Tocilizumab (Actemra) in combination with a short-term prednisone administration for the treatment of newly diagnosed giant cell arteritis.

Italy, Switzerland (ICTRP)

ICTRP Trial ID
NCT03745586 (ICTRP)

Official title (approved by ethics committee)
A proof of concept study to assess the efficacy of Tocilizumab in combination with ultra-short glucocorticoid administration to treat newly diagnosed Giant Cell Arteritis (BASEC)

Academic title
Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab (ICTRP)

Public title
Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab (ICTRP)

Disease under investigation
Giant Cell Arteritis
(ICTRP)

Intervention under investigation
Drug: Tocilizumab
Drug: Glucocorticoids
(ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria

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)
(ICTRP)

not available

Primary and secondary end points
Remission
(ICTRP)

Time to first relapse
Remission
(ICTRP)

Registration date
06.11.2018 (ICTRP)

Incorporation of the first participant
01.12.2018 (ICTRP)

Secondary sponsors
not available

Additional contacts
Peter Villiger, Prof, University of Bern (ICTRP)

Secondary trial IDs
2018-00845 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://trialsearch.who.int/Trial2.aspx?TrialID=NCT03745586 (ICTRP)