Giant Cell Arteritis (GCA)Phase 2NCT07108387
Tocilizumab Discontinuation Versus Dose Reduction for Patients With Well-Controlled Giant Cell Arteritis
A Phase 2 study testing Tocilizumab and Discontinue Tocilizumab in people with Giant Cell Arteritis (GCA), run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial summary
This is a multi-center, randomized, open label study that will assess the efficacy and safety of ACTEMRA(R) or one of its FDA-approved biosimilars Tocilizumab (TCZ) maintenance versus withdrawal in Giant cell arteritis (GCA) patients who are in remission after at least 12 months of high dose TCZ treatment. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Giant Cell Arteritis (GCA)
- What is being tested?
- Tocilizumab and Discontinue Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 7 sitesUnited States
- Study dates
- 5 Jan 2026to 11 Jan 2030
- Phase
- Phase 2
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 Giant cell arteritis (GCA) classified according to the following criteria:
- AND at least one of the following:
- Cranial signs or 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:
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- 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 ultrasound (US), Magnetic resonance angiography (MRA), computerized tomography angiography (CTA), or Positron emission tomography-computerized tomography (PET-CT)
- Ultrasound (US) or Magnetic resonance imaging (MRI) or PET/CT demonstration of features of GCA in a cranial artery
- Glucocorticoid-free remission on Tacrolimus (TCZ) therapy according to the following criteria:
- Ongoing treatment with TCZ (ACTEMRA(R) or one of its FDA-approved biosimilars) administered at 6-8 mg/kg IV every 4 weeks OR 162 mg subcutaneous (SC) weekly for at least 12 months prior to randomization. Participants cannot have missed more than one SC dose or any Intravenously (IV) doses in the 2 months prior to randomization
- Disease remission for at least 12 months prior to randomization defined as the absence of clinical signs or symptoms of active GCA and Polymyalgia rheumatica (PMR) along with normal values of C-reactive protein (CRP) (< 10 mg/L) at screening
- Absence of oral, IV, intramuscular (IM), or SC glucocorticoid treatment for at least 3 months prior to randomization
Who cannot join
- An autoimmune disease or other condition, other than Giant cell arteritis (GCA), that requires/is anticipated to require chronic or recurrent oral or parenteral glucocorticoids or other immunomodulatory therapy. (Topical, intra-articular, and inhaled therapies are acceptable)
- Hospitalization within 8 weeks prior to randomization
- Suspected or established adrenal insufficiency
- Treatment with any investigational agent within 12 months of randomization
- Concomitant treatment with another biologic immunosuppressant (e.g., etanercept, adalimumab, infliximab, certolizumab, golimumab, sarilumab, abatacept, rituximab, or secukinumab) within 12 months prior to randomization. Concomitant treatment with non-biologic immunosuppressants (e.g.
- JAK inhibitors, Methotrexate (MTX)) within 3 months prior to randomization. An exception is hydroxychloroquine, which is permitted as long as the dose has been stable for the 8 weeks preceding randomization
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- Immunization with a live/attenuated vaccine within <= 4 weeks prior to randomization
- History of severe allergic or anaphylactic reactions to Tocilizumab (TCZ) or to prednisone (or equivalent)
- 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
- Serologic evidence of chronic hepatitis infection at time of TCZ initiation or at screening if not previously assessed:
- Evidence of current or prior infection with hepatitis B, as indicated by a positive test for the hepatitis B surface antigen or an isolated positive test for the hepatitis B core antibody. If a participant has an isolated positive hepatitis B core antibody, clearance after consultation with infectious disease specialist or gastroenterologist/hepatologist must be obtained
- Evidence of current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response >= 12 weeks. If a participant has a positive or indeterminate hepatitis C antibody, viral load testing (e.g., reflex testing) is required. Clearance after consultation with infectious disease specialist or gastroenterologist/hepatologist must be obtained
- Positive interferon gamma release assay (IGRA) (e.g., QuantiFERON Gold or equivalent) at time of TCZ initiation or at screening if not previously assessed
- If the participant has had the BCG vaccine or has some other condition complicating the interpretation of tuberculosis (TB) testing, clearance after consultation with infectious disease specialist or pulmonologist must be obtained
- Participants diagnosed with latent TB are eligible but must have initiated appropriate prophylaxis for at least 30 days prior to initiation of study treatment
- Indeterminate IGRA must be repeated (with same or other IGRA per local policy) and shown to be negative. Alternatively, if the IGRA remains indeterminate, a participant must have a negative tuberculin purified protein derivative skin test (PPD) or clearance after consultation with infectious disease specialist or pulmonologist.
- Known active bacterial, viral, fungal, mycobacterial, or other infections except fungal infections of the nail beds and superficial cutaneous infection treated topically
- Participant is pregnant or breastfeeding or planning a pregnancy while enrolled in the study
- Any infection requiring treatment with IV antibiotics within 4 weeks of randomization or oral antibiotics within 2 weeks of randomization
- Active treatment for malignancy at the time of randomization, with exception of prophylactic hormonal therapy (e.g. prostate cancer, breast cancer, etc.)
- History of alcohol, drug, or chemical abuse within 12 months prior to randomization
- History of chronic or recurrent infection (excluding simple cystitis, viral respiratory infection, sinusitis, dermatophyte (tinea) infection) within 12 months prior to randomization
- History of opportunistic infection within 12 months prior to randomization unless evaluated and cleared by an infectious disease or pulmonary specialist
- Any of the following laboratory values during screening:
- Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) > 1.5 × upper limit of normal (ULN)
- Platelet count < 100 × 10^9/L (100,000/mm^3)
- Hemoglobin (Hb) < 90 g/L (9 g/dL; 5.6 mmol/L)
- White blood cells < 3.0 × 10^9/L (3000/mm^3)
- Absolute neutrophil count (ANC) < 1.0 × 10^9/L (1000/mm^3)
- Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Emory University School of Medicine: Division of Rheumatology
Atlanta, Georgia, 30307
Chris Chin, 404-712-2874, chris.chi.chin@emory.edu
Athanasios Tiliakos, DO
- Recruiting
Johns Hopkins Hospital: Division of Rheumatology Vasculitis Center
Baltimore, Maryland, 21287
Hannah Smith, 410-550-2044, Hsmith97@jh.edu
Brendan Antiochos
- Recruiting
Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
Boston, Massachusetts, 02114
Joseph Sadok, 617-724-8048, jsadok@mgh.harvard.edu
Sebastian Unizony, MD
- Recruiting
Northwestern University
Chicago, Illinois, 60611
John Seagrist, 312-503-0565, john.seagrist@northwestern.edu
Anisha Dua, MD
- Recruiting
Northwell Health: Division of Rheumatology and Allergy-Clinical Immunology
Great Neck, New York, 11021
Mohini Doobay, 516-708-2546, MDoobay1@northwell.edu
Lara El Khoury, MD
- Recruiting
Hospital for Special Surgery, New York: Division of Rheumatology
New York, New York, 10021
Janvi Bhatia, 212-774-2123, bhatiaj@hss.edu
Lindsay Lally, MD
- Recruiting
University of Pittsburgh Medical Center: Division of Rheumatology and Clinical Immunology
Pittsburgh, Pennsylvania, 15217
Emily Matone, 412-465-0242, emm518@pitt.edu
Robyn E. Domsic, MD
About this study
Official title: A Randomized Study of Tocilizumab Discontinuation for Patients With Giant Cell Arteritis in Remission (AGA01)
This is a multi-center, randomized, open label study that will assess the efficacy and safety of ACTEMRA(R) or one of its FDA-approved biosimilars Tocilizumab (TCZ) maintenance versus withdrawal in Giant cell arteritis (GCA) patients who are in remission after at least 12 months of high dose TCZ treatment. Eligible participants will also have discontinued glucocorticoids (e.g., prednisone (or equivalent)) entirely at least three months before randomization. High dose TCZ treatment includes 6-8 mg/kg intravenously (IV) monthly or 162 mg subcutaneously (SC) weekly, which are two forms of administration that are commonly used in clinical practice and are equally efficacious in controlling GCA
This research study has three parts:
Read more
- The screening phase (up to 42 days) consists of collecting information about your health and your GCA, a physical exam, and blood tests to see If you qualify to enroll in the study
- The study treatment phase (withdrawal/step down dosing phase study months 0 - 18) consists of you either completely stopping or decreasing your current dose of tocilizumab while collecting information about your health and your GCA as well as blood samples every two months at clinic visits
- The safety follow-up phase (months 19-30) consists of collecting information about your health and your GCA as well as blood samples every three months
The primary objective is to determine the rate of disease relapse at 18 months in participants with GCA who receive low-dose TCZ compared to those who discontinue TCZ
- Conditions
- Giant Cell Arteritis (GCA)
- Being tested
- Tocilizumab, Discontinue Tocilizumab
- Keywords
- Tocilizumab, Giant Cell Arteritis, ACTEMRA(R)
- 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
Participants will continue Tocilizumab (TCZ) at a lower dose of either 4 mg/kg IV monthly or 162 mg SC every 2 weeks
Participants randomized to the stepped-down treatment arm will receive TCZ on their current route of administration. The route of administration may change if needed during study participation at the discretion of the investigator
Discontinue TocilizumabDrug
Also called ACTEMRA
Participants will discontinue Tocilizumab and will have visits at Week 2, Month 1 and 2, and then every 2 months during the TCZ Withdrawal Phase until the Month 18 Visit.
Participants who remain in remission will enter the Follow-Up Phase for an additional 12 months at Month 18 and will continue withdrawal at that time.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab Step-Down Dosing Arm | Experimental | Randomization will be performed within strata defined by gender, whether the participant has a history of Giant cell arteritis (GCA) relapse, and whether the participant has a history of polymyalgia rheumatica (PMR) symptoms.
Patients in remission of high dose Tocilizumab (TCZ) >=12months and discontinued glucocorticoids (e.g. prednisone) >=3 months will receive 162mg subcutaneously (SC) every 2 weeks or 4mg/Kg intravenously (IV) monthly for 18 months
Participants who remain in remission will enter the Follow-Up Phase for an additional 12 months at Month 18 and will discontinue TCZ at that time Receives: Drug: Tocilizumab |
| Tocilizumab Withdrawal Arm | Other | Randomization will be performed within strata defined by gender, whether the participant has a history of Giant cell arteritis (GCA) relapse, and whether the participant has a history of PMR symptoms.
Patients in remission of high dose Tocilizumab (TCZ) >=12months and discontinued glucocorticoids (e.g. prednisone) >=3 months will discontinue Tocilizumab and will have visits at Week 2, Month 1 and 2, and then every 2 months during the TCZ Withdrawal Phase until the Month 18 Visit.
Participants who remain in remission will enter the Follow-Up Phase for an additional 12 months at Month 18 and will continue withdrawal at that time. Receives: Drug: Discontinue Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients in sustained remission
Sustained remission and clinical relapse will be determined by the investigator based on clinical signs and symptoms of active Giant cell arteritis (GCA) and PMR regardless of the values of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The absence of clinical signs and symptoms of active GCA and PMR over the TCZ Withdrawal/Step-Down Dosing and Follow-Up Phases will define sustained remission through Months 18 and 30, respectively. Clinical relapse will be based on recurrent signs or symptoms attributed to GCA regardless of the values of ESR and CRP. To fulfill the definition of a disease relapse, the investigator must make the decision to intensify the participants GCA treatment
Measured: Through Month 18
Secondary outcomes (12)
Time to disease relapse
Measured: Through Month 30
Number of disease relapses
Measured: At Months 18 and 30
Annualized relapse rate
Measured: At Months 18 and 30
Cumulative prednisone (or equivalent) dose
Measured: At Months 18 and 30
Cumulative Glucocorticoid Toxicity Index (GTI) excluding the bone density domain
calculated as the cumulative worsening score (CWS) and aggregate improvement score (AIS)
Measured: At Months 18 and 30
Clinical features of disease relapse
Sustained remission and clinical relapse will be determined by the investigator based on clinical signs and symptoms of active Giant cell arteritis (GCA) and PMR regardless of the values of ESR and CRP. The absence of clinical signs and symptoms of active GCA and PMR over the TCZ Withdrawal/Step-Down Dosing and Follow-Up Phases will define sustained remission through Months 18 and 30, respectively. Clinical relapse will be based on recurrent signs or symptoms attributed to GCA regardless of the values of ESR and CRP. To fulfill the definition of a disease relapse, the investigator must make the decision to intensify the participants GCA treatment
Measured: Through Month 30
The number of Adverse Events (AEs)
Measured: At Months 18 and 30
The nature of Adverse Events (AEs)
Measured: At Months 18 and 30
The severity of Adverse Events (AEs)
Measured: At Months 18 and 30
The number of Serious Adverse Events (SAEs)
Measured: At Months 18 and 30
The nature of Serious Adverse Events (SAEs)
Measured: At Months 18 and 30
Proportion of patients in sustained remission
Measured: Through Month 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2025
- Study start5 Jan 2026
- Primary completion11 Jun 2027 (estimated)
- Study completion11 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Giant Cell Arteritis (GCA)Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sebastian H Unizony, M.D., Study chair, Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07108387
- Sponsor's protocol ID
- DAIT AGA01
- Status last verified
- Aug 2026
- First submitted
- 18 Jul 2025
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.