Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab (GUSTO)
Primary Purpose
Giant Cell Arteritis
Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Tocilizumab
Glucocorticoids
Sponsored by
About this trial
This is an interventional treatment trial for Giant Cell Arteritis
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- History of severe allergic or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of tocilizumab
- 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)
- Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology
- Positive Quantiferon-TB test for latent Tb without subsequent INH prophylaxis
- Patients with active Tb which had to be treated for Tb within 2 years before the screening visit
- Absolute neutrophil count (ANC) < 2.0 x 103/L, white blood cells < 2.5 x 103/L, platelet count < 100,000/L
- Hemoglobin < 8.0 g/dL
- Concentrations of serum IgG and/or IgM below 5.0 mg/mL and 0.40 mg/mL, respectively
- Serum creatinine > 2.0 mg/dL
- Alanine aminotransferase (ALT) or aspartate amino-transferase (AST) > 1.5 times the upper limit of normal (ULN)
- Total bilirubin > 1.5 times the upper limit of normal (ULN)
- Triglycerides > 400 mmol/dL (non-fasted) or > 250 mmol/dL (fasted) at screening
- 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)
- Technical implants such as cardiac pacemakers (for MR-angiogram)
- Claustrophobia (for MR-angiogram)
- Known allergy against the contrast media (Multihance® or Dotarem® as alternative)
Sites / Locations
- University Hospital Bern, Inselspital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All study participants
Arm Description
Outcomes
Primary Outcome Measures
Remission
Proportion of patients achieving remission within 31 days and without relapse until week 24
Secondary Outcome Measures
Remission
Proportion of patients with complete relapse-free remission of disease at week 24 and at week 52
Time to first relapse
Time to first relapse
Full Information
NCT ID
NCT03745586
First Posted
November 6, 2018
Last Updated
June 21, 2021
Sponsor
Insel Gruppe AG, University Hospital Bern
1. Study Identification
Unique Protocol Identification Number
NCT03745586
Brief Title
Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
Acronym
GUSTO
Official Title
Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
December 1, 2018 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
March 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Giant Cell Arteritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All study participants
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Intervention Description
Day 3: Tocilizumab infusion (8mg/kg body-weight) Day 10- week 52: Tocilizumab s.c. injections (162mg) in weekly intervals
Intervention Type
Drug
Intervention Name(s)
Glucocorticoids
Intervention Description
Day0-day2: methylprednisolone 500mg i.v.
Primary Outcome Measure Information:
Title
Remission
Description
Proportion of patients achieving remission within 31 days and without relapse until week 24
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Remission
Description
Proportion of patients with complete relapse-free remission of disease at week 24 and at week 52
Time Frame
Week 24 and week 52
Title
Time to first relapse
Description
Time to first relapse
Time Frame
through study completion, an average of 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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)
History of severe allergic or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of tocilizumab
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)
Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology
Positive Quantiferon-TB test for latent Tb without subsequent INH prophylaxis
Patients with active Tb which had to be treated for Tb within 2 years before the screening visit
Absolute neutrophil count (ANC) < 2.0 x 103/L, white blood cells < 2.5 x 103/L, platelet count < 100,000/L
Hemoglobin < 8.0 g/dL
Concentrations of serum IgG and/or IgM below 5.0 mg/mL and 0.40 mg/mL, respectively
Serum creatinine > 2.0 mg/dL
Alanine aminotransferase (ALT) or aspartate amino-transferase (AST) > 1.5 times the upper limit of normal (ULN)
Total bilirubin > 1.5 times the upper limit of normal (ULN)
Triglycerides > 400 mmol/dL (non-fasted) or > 250 mmol/dL (fasted) at screening
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)
Technical implants such as cardiac pacemakers (for MR-angiogram)
Claustrophobia (for MR-angiogram)
Known allergy against the contrast media (Multihance® or Dotarem® as alternative)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Villiger, Prof
Organizational Affiliation
University of Bern
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Bern, Inselspital
City
Bern
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34117737
Citation
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.
Results Reference
derived
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Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
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