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Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab (GUSTO)

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ClinicalTrials.gov Identifier: NCT03745586
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : January 17, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

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.


Condition or disease Intervention/treatment Phase
Giant Cell Arteritis Drug: Tocilizumab Drug: Glucocorticoids Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
Actual Study Start Date : December 1, 2018
Estimated Primary Completion Date : November 30, 2020
Estimated Study Completion Date : August 1, 2021


Arm Intervention/treatment
Experimental: All study participants Drug: Tocilizumab
Day 3: Tocilizumab infusion (8mg/kg body-weight) Day 10- week 52: Tocilizumab s.c. injections (162mg) in weekly intervals

Drug: Glucocorticoids
Day0-day2: methylprednisolone 500mg i.v.




Primary Outcome Measures :
  1. Remission [ Time Frame: Week 24 ]
    Proportion of patients achieving remission within 31 days and without relapse until week 24


Secondary Outcome Measures :
  1. Remission [ Time Frame: Week 24 and week 52 ]
    Proportion of patients with complete relapse-free remission of disease at week 24 and at week 52

  2. Time to first relapse [ Time Frame: through study completion, an average of 1 year ]
    Time to first relapse



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745586


Contacts
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Contact: Peter M Villiger, Prof +41 (0)31 632 98 40 peter.villiger@insel.ch

Locations
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Italy
Department of Rheumatology Not yet recruiting
Reggio Emilia, Italy
Contact: Carlo Salvarani, Prof         
Switzerland
University Hospital Bern, Inselspital Recruiting
Bern, Switzerland
Contact: Peter Villiger, Prof         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
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Principal Investigator: Peter Villiger, Prof University of Bern

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT03745586     History of Changes
Other Study ID Numbers: 2018-00845
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: January 17, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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

Additional relevant MeSH terms:
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Connective Tissue Diseases
Arteritis
Giant Cell Arteritis
Polymyalgia Rheumatica
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs