Giant Cell ArteritisPhase 1/2GUSTONCT03745586
Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
A Phase 1/2 study testing Tocilizumab and Glucocorticoids in people with Giant Cell Arteritis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Giant Cell Arteritis
- What is being tested?
- Tocilizumab and Glucocorticoids
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Dec 2018to 1 Mar 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Tocilizumab, Glucocorticoids
- Medical subject headings
- Giant Cell Arteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Day 3: Tocilizumab infusion (8mg/kg body-weight) Day 10- week 52: Tocilizumab s.c. injections (162mg) in weekly intervals
GlucocorticoidsDrug
Day0-day2: methylprednisolone 500mg i.v.
| Study group | Role | What they receive |
|---|---|---|
| All study participants | Experimental | Not described Receives: Drug: Tocilizumab; Drug: Glucocorticoids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission
Proportion of patients achieving remission within 31 days and without relapse until week 24
Measured: Week 24
Secondary outcomes (2)
Remission
Proportion of patients with complete relapse-free remission of disease at week 24 and at week 52
Measured: Week 24 and week 52
Time to first relapse
Time to first relapse
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start1 Dec 2018
- Primary completion30 Nov 2020
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Giant Cell ArteritisStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Villiger, Prof, Principal investigator, University of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03745586
- Sponsor's protocol ID
- 2018-00845
- Other IDs
- 2018
- Acronym
- GUSTO
- Status last verified
- Jun 2021
- First submitted
- 6 Nov 2018
- Last updated
- 22 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38287611Christ 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.
PubMed 37287970Seitz 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.
PubMed 34117737
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
- ClinicalTrials.gov ID
- NCT03745586
- Acronym / sponsor ID
- GUSTO / 2018-00845
- Conditions
- Giant Cell Arteritis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All study participants | Experimental | Drug: Tocilizumab, Drug: Glucocorticoids |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (31 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabDay 3: Tocilizumab infusion (8mg/kg body-weight) Day 10- week 52: Tocilizumab s.c. injections (162mg) in weekly intervals | Drug | All study participants |
| GlucocorticoidsDay0-day2: methylprednisolone 500mg i.v. | Drug | All study participants |
Primary outcome
Remission
Time frame: Week 24
Proportion of patients achieving remission within 31 days and without relapse until week 24
2 secondary outcomes
Remission
Time frame: Week 24 and week 52
Time to first relapse
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- Derived from this study: PubMed 38287611Christ 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.
- Derived from this study: PubMed 37287970Christ 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.
- Derived from this study: PubMed 34117737Seitz 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Villiger, Prof principal investigator
University of Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tocilizumab and Glucocorticoids in people with Giant Cell Arteritis, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03745586, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.