Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab

NCT03745586 | Completed Phase 1 DMC

• 1 other identifier: 2018-00845
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Remission

  Proportion of patients achieving remission within 31 days and without relapse until week 24

  Week 24

Secondary Outcomes (2)

• Remission

  Week 24 and week 52

• Time to first relapse

  through study completion, an average of 1 year

Study Arms (1)

All study participants

EXPERIMENTAL

Drug: Tocilizumab; Drug: Glucocorticoids

Interventions

Tocilizumab DRUG

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

All study participants

Glucocorticoids DRUG

Day0-day2: methylprednisolone 500mg i.v.

All study participants

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• Patient's written informed consent.

You may not qualify if:

• Rheumatic diseases (except for CPPD/chondrocalcinosis) other than GCA or polymyalgia rheumatica (i.e., RA, autoimmune connectivitides, other systemic vasculitides, a.o.)
• Chronic use of systemic CS with inability, in the opinion of the investigator, to withdraw CS treatment at day 4 according to protocol
• 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
• Any condition or general state of health which, in the Investigator's opinion, would preclude participation in the study
• Actual or recent myocardial infarction (within the last 3 months before screening visit)
• 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
• Uncontrolled disease (such as asthma, psoriasis or inflammatory bowel disease) where flares are commonly treated with oral or injectable corticosteroids
• 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
• History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks before screening visit
• Any surgical procedure, including bone/joint surgery within 8 weeks prior before screening visit or planned within the duration of the study
• 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
• Lack of peripheral venous access
• Body weight \> 150 kg or BMI \> 35
• Previous treatment with tocilizumab or any other biological agent within last 6 months before screening visit; Rituximab within 12 months before screening visit
• Treatment with any investigational agent within 28 days of screening visit or 5 half-lives of the investigational drug (whichever is the longer)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

University Hospital Bern, Inselspital

Bern, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 38287611 DERIVED

• 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.

  PMID: 37287970 DERIVED

• 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.

  PMID: 34117737 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

tocilizumab; Glucocorticoids

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Peter Villiger, Prof

  University of Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2018
• First Posted: November 19, 2018
• Study Start: December 1, 2018
• Primary Completion: November 30, 2020
• Study Completion: March 1, 2021
• Last Updated: June 22, 2021

Record last verified: 2021-06

Locations

CH (1)