- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03726749
Tocilizumab Plus a Short Prednisone Taper for GCA
Tocilizumab Plus a Short Prednisone Taper for Giant Cell Arteritis (GCA)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a single center, open label study that will assess the efficacy and safety of 52 weeks of tocilizumab (TCZ) in combination with 8-weeks of prednisone in 30 patients with active giant cell arteritis (GCA). Active disease is defined as signs and/or symptoms of GCA plus increased inflammatory markers (e.g., erythrosedimentation rate [ESR] and/or C-reactive protein [CRP]).
The study will enroll subjects with new onset and with relapsing/refractory GCA, and consist of a screening phase (up to 6 weeks), a treatment phase (52 weeks) and a safety follow up phase (4 weeks).
The primary endpoint of the study, sustained remission, will be assessed at week 52.
The definition of sustained remission contains 3 elements:
- Absence of clinical signs and symptoms of active GCA along with the normalization of the ESR (< 40 mm/hour) and CRP (< 10 mg/L).
- Completion of the pre-specified prednisone taper protocol
- Absence of disease flare (relapse) since the induction of remission by week 8.
Disease flare is defined as the re-appearance of unequivocal signs or symptoms of active GCA (with or without elevation of ESR and/or CRP) or the elevation of the ESR and/or CRP that is thought to be due to active GCA and that requires escape therapy.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Ability and willingness to provide written informed consent and to comply with the study protocol
Diagnosis of GCA classified per the following criteria:
• Age 50 years or older
AND at least one of the following:
- Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp tenderness, temporal artery tenderness or decreased pulsation, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication)
- Symptoms of polymyalgia rheumatica (PMR), defined as shoulder and / or hip girdle pain associated with inflammatory morning stiffness
AND at least one of the following:
- Cranial artery biopsy revealing features of GCA (e.g., mononuclear cell infiltration or granulomatous inflammation).
- Evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as Image result for magnetic resonance angiogram (MRA), Computed tomography angiography (CTA) , or Image result for positron emission tomography (PET) and computed tomography (CT) (PET-CT)
- Ultrasound demonstration of features of GCA in a cranial artery.
New-onset or relapsing/refractory active disease defined as follows:
- New onset: diagnosis of GCA within 6 weeks of baseline visit
- Relapsing/refractory: diagnosis of GCA > 6 weeks before baseline visit
AND
• Active GCA within 6 weeks of baseline visit defined as the presence of clinical signs and symptoms [cranial or PMR] and erythrocyte sedimentation rate (ESR) ≥ 30 mm/hour or C-reactive protein (CRP) ≥ 10 mg/L)
Exclusion Criteria:
General exclusion criteria
- Major surgery within 8 weeks prior to screening or planned major surgery within 12 months after randomization
- Transplanted organs (except corneal transplant performed more than 3 months prior to screening)
- Major ischemic event, unrelated to GCA, within 12 weeks of screening
Exclusions related to prior or concomitant therapy*
- Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
- Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to Campath (alemtuzumab), anti-CD4 (cluster of differentiation 4), anti-CD5, anti-CD3, anti-CD19, and anti-CD20
- Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation
- Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to baseline
- Treatment with cyclosporine A, azathioprine, cyclophosphamide or Mycophenolate mofetil (MMF) within 4 weeks of baseline. Patients on methotrexate at screening will require discontinuation of this agent prior to baseline visit.
- Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline
- Patients requiring systemic glucocorticoid therapy for conditions other than GCA, which, in the opinion of the investigator, would interfere with adherence to the fixed glucocorticoid taper regimen and/or to assessment of efficacy in response to TCZ
Inability, in the opinion of the investigator, to withdraw GC treatment through protocol-defined taper regimen due to suspected or established adrenal insufficiency
- Patients treated with TCZ before will be permitted to participate in the trial if they demonstrated treatment efficacy and they did not discontinue TCZ because of an adverse effect.
Exclusions related to general safety
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or to prednisone
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal (GI) disease
- Current liver disease, as determined by the investigator
- History of diverticulitis or active chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds)
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- Active TB requiring treatment within the previous 3 years. Patients treated for TB with no recurrence within 3 years are eligible
- Untreated latent TB infection (LTBI). Patients should be screened for latent TB and, if positive, treated according to local practice guidelines prior to initiating TCZ treatment. Patients treated for LTBI within 3 years are eligible. Patients with current LTBI are eligible for enrollment one month after initiating treatment for LTBI.
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of malignant disease or malignancies diagnosed within the previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that have been excised and cured)
- Females of childbearing potential and females who are breastfeeding
- Males of reproductive potential who are not willing to use an effective method of contraception, such as condom, sterilization, or true abstinence throughout study and for a minimum of 6 months after study drug therapy
- History of alcohol, drug, or chemical abuse within 1 year prior to screening
Laboratory exclusions
- ALT or AST > 1.5 × upper limit of normal (ULN)
- Total bilirubin > ULN
- Platelet count < 100× 109/L (100,000/mm3)
- Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
- White blood cells < 3.0 × 109/L (3000/mm3)
- Absolute neutrophil count < 1.0 × 109/L (1000/mm3)
- Absolute lymphocyte count < 0.5 × 109/L (500/mm3)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Tocilizumab and prednisone
|
Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor
Other Names:
Prednisone is an anti-inflammatory medication
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sustained Remission
Time Frame: 52 weeks
|
Number and percentage of patients in sustained remission by week 52.
Sustained remission was defined as the absence of disease flare between baseline and week 52.
Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
|
52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Flares
Time Frame: 52 Weeks
|
Total number of disease flares by week 52.
Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
|
52 Weeks
|
Cumulative Prednisone Dose
Time Frame: 52 Weeks
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Cumulative prednisone dose (mg) by week 52
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52 Weeks
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Adverse Events
Time Frame: 52 weeks
|
Number and percentage of participants with at least one adverse event by week 52
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52 weeks
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Serious Adverse Events
Time Frame: 52 weeks
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Number and percentage of participants with at least one serious adverse event by week 52
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52 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Ana D Fernandes, MA, Massachusetts General Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Immune System Diseases
- Autoimmune Diseases of the Nervous System
- Autoimmune Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Muscular Diseases
- Vasculitis
- Skin Diseases, Vascular
- Vasculitis, Central Nervous System
- Polymyalgia Rheumatica
- Giant Cell Arteritis
- Arteritis
- Physiological Effects of Drugs
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Prednisone
- Glucocorticoids
Other Study ID Numbers
- ML40859
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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