Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab

NCT ID: NCT03745586

Last Updated: 2021-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2021-03-01

Brief Summary

Two recent RCTs showed the ability of tocilizumab to induce and maintain remission of giant cell arteritis. Both studies used the dosing schemes for Rheumatoid Arthritis (i.e. 8mg/kg bodyweight i.v. in 4-weekly intervals and 162mg weekly s.c., respectively). In both trials glucocorticoids (GC) were initially administrated at medium to high doses with subsequent rapid reduction and discontinuation over 24 weeks. In case of relapse, GC doses were re-increased.

The results of both studies suggest that GC could be reduced more rapidly. This would further reduce GC-induced adverse effects.

Thus, the investigators propose to perform an open label single arm study to assess the efficacy of ultra-short co-medication with GC, using Simon's minimax two-stage design.

Conditions

Giant Cell Arteritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All study participants

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Day 3: Tocilizumab infusion (8mg/kg body-weight) Day 10- week 52: Tocilizumab s.c. injections (162mg) in weekly intervals

Glucocorticoids

Intervention Type: DRUG

Day0-day2: methylprednisolone 500mg i.v.

Interventions

Tocilizumab

Day 3: Tocilizumab infusion (8mg/kg body-weight) Day 10- week 52: Tocilizumab s.c. injections (162mg) in weekly intervals

Intervention Type: DRUG

Glucocorticoids

Day0-day2: methylprednisolone 500mg i.v.

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Villiger, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Bern

Locations

University Hospital Bern, Inselspital

Bern, , Switzerland

Countries

Switzerland

References

Christ L, Seitz L, Scholz G, Sarbu AC, Amsler J, Butikofer L, Tappeiner C, Kollert F, Reichenbach S, Villiger PM. Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-label, proof-of-concept study. Lancet Rheumatol. 2021 Sep;3(9):e619-e626. doi: 10.1016/S2665-9913(21)00152-1. Epub 2021 Jul 2.

Reference Type: DERIVED

PMID: 38287611 (View on PubMed)

Christ L, Gloor AD, Kollert F, Gaber T, Buttgereit F, Reichenbach S, Villiger PM. Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial). Front Immunol. 2023 May 23;14:1165758. doi: 10.3389/fimmu.2023.1165758. eCollection 2023.

Reference Type: DERIVED

PMID: 37287970 (View on PubMed)

Seitz L, Christ L, Lotscher F, Scholz G, Sarbu AC, Butikofer L, Kollert F, Schmidt WA, Reichenbach S, Villiger PM. Quantitative ultrasound to monitor the vascular response to tocilizumab in giant cell arteritis. Rheumatology (Oxford). 2021 Nov 3;60(11):5052-5059. doi: 10.1093/rheumatology/keab484.

Reference Type: DERIVED

PMID: 34117737 (View on PubMed)

Other Identifiers

2018-00845

Identifier Type: -

Identifier Source: org_study_id