Giant Cell ArteritisPhase 4NCT03726749
Tocilizumab Plus a Short Prednisone Taper for GCA
A Phase 4 study testing Tocilizumab and Prednisone in people with Giant Cell Arteritis, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This is an open-label pilot study of tocilizumab (TCZ) 162 mg weekly administered subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone. 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 Prednisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2018to 29 Dec 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Tocilizumab Plus a Short Prednisone Taper for Giant Cell Arteritis (GCA)
This is an open-label pilot study of tocilizumab (TCZ) 162 mg weekly administered subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone.
Read the 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.
- Conditions
- Giant Cell Arteritis
- Being tested
- Tocilizumab, Prednisone
- Keywords
- GCA, Tocilizumab, Prednisone
- 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
Also called ACTEMRA®
Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor
PrednisoneDrug
Also called Glucocorticoids
Prednisone is an anti-inflammatory medication
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab and prednisone | Experimental | 1. TCZ 162 mg administered by subcutaneous injection weekly for 52 weeks.
2. Prednisone taper over 8 weeks with a starting dose between 20 and 60 mg. Receives: Drug: Tocilizumab; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Remission
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)
Measured: 52 weeks
Secondary outcomes (4)
Disease Flares
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)
Measured: 52 Weeks
Cumulative Prednisone Dose
Cumulative prednisone dose (mg) by week 52
Measured: 52 Weeks
Adverse Events
Number and percentage of participants with at least one adverse event by week 52
Measured: 52 weeks
Serious Adverse Events
Number and percentage of participants with at least one serious adverse event by week 52
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2018
- Study start28 Nov 2018
- Primary completion15 Dec 2021
- Study completion29 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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 Massachusetts General HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Roche-Genentech
- Responsible party
- Principal investigator, Sebastian H Unizony, MD, Massachusetts General Hospital
- Investigators
- Ana D Fernandes, MA, Study chair, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03726749
- Sponsor's protocol ID
- ML40859
- Status last verified
- Nov 2022
- First submitted
- 30 Oct 2018
- Last updated
- 2 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Unizony S, Matza MA, Jarvie A, O'Dea D, Fernandes AD, Stone JH. Treatment for giant cell arteritis with 8 weeks of prednisone in combination with tocilizumab: a single-arm, open-label, proof-of-concept study. Lancet Rheumatol. 2023 Dec;5(12):e736-e742. doi: 10.1016/S2665-9913(23)00265-5. Epub 2023 Nov 2.
PubMed 38251564
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tocilizumab Plus a Short Prednisone Taper for Giant Cell Arteritis (GCA)
- ClinicalTrials.gov ID
- NCT03726749
- Acronym / sponsor ID
- ML40859
- Conditions
- Giant Cell Arteritis
- Keywords
- GCA, Tocilizumab, Prednisone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Roche-Genentech
- Study start
- 28 Nov 2018 (actual)
- Primary completion
- 15 Dec 2021 (actual)
- Study completion
- 29 Dec 2021 (actual)
- First posted
- 31 Oct 2018 (actual)
- Results
- Posted 2 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label pilot study of tocilizumab (TCZ) 162 mg weekly administered subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab and prednisone | Experimental | Drug: Tocilizumab, Drug: Prednisone1. TCZ 162 mg administered by subcutaneous injection weekly for 52 weeks. 2. Prednisone taper over 8 weeks with a starting dose between 20 and 60 mg. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Ability and willingness to provide written informed consent and to comply with the study protocol
- Diagnosis of GCA classified per the following criteria:
- New-onset or relapsing/refractory active disease defined as follows:
- 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)
Key exclusion criteria (36 listed)
- General exclusion criteria
- Exclusions related to prior or concomitant therapy*
- Exclusions related to general safety
- Laboratory exclusions
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 |
|---|---|---|
| TocilizumabAlso: ACTEMRA®Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor | Drug | Tocilizumab and prednisone |
| PrednisoneAlso: GlucocorticoidsPrednisone is an anti-inflammatory medication | Drug | Tocilizumab and prednisone |
Primary outcome
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)
4 secondary outcomes
Disease Flares
Time frame: 52 Weeks
Cumulative Prednisone Dose
Time frame: 52 Weeks
Adverse Events
Time frame: 52 weeks
Serious Adverse Events
Time frame: 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38251564Unizony S, Matza MA, Jarvie A, O'Dea D, Fernandes AD, Stone JH. Treatment for giant cell arteritis with 8 weeks of prednisone in combination with tocilizumab: a single-arm, open-label, proof-of-concept study. Lancet Rheumatol. 2023 Dec;5(12):e736-e742. doi: 10.1016/S2665-9913(23)00265-5. Epub 2023 Nov 2.
- Individual participant dataSharing planned: No
Related trials for Giant Cell Arteritis
Not yet recruitingPhase 3
Aspirin for the Prevention of Ischemic Complications in Giant Cell Arteritis
Giant Cell Arteritis (GCA), Acute Coronary Syndrome (ACS)
RecruitingObservational study
Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
Takayasu's Arteritis, Giant Cell Arteritis
Active, not recruitingObservational study
The Applanation Tonometry in GCA Pilot
Giant Cell Arteritis
RecruitingObservational study
Optic Nerve Sheath Ultrasound in Giant Cell Arteritis
Giant Cell Arteritis, Anterior Ischemic Optic Neuropathy
RecruitingObservational study
Early Temporal Dynamics of Optic Nerve Sheath Diameter After Therapy in GCA
Giant Cell Arteritis, Temporal Arteritis
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.
Ana D Fernandes, MA study chair
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tocilizumab and Prednisone in people with Giant Cell Arteritis, run by Massachusetts General Hospital at 1 site in United States.
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 15 inclusion and 36 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 2 Dec 2022. 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 United States. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Sustained Remission (time frame: 52 weeks). 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 NCT03726749, which also lists 1 linked publication.
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 2 Dec 2022; AzTrials last refreshed its copy on 1 Nov 2026.