Tocilizumab Discontinuation Versus Dose Reduction for Patients With Well-Controlled Giant Cell Arteritis

NCT07108387 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT AGA01
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 7

Brief 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. 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:

1. 1.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
2. 2.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
3. 3.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

Conditions

Giant Cell Arteritis (GCA)

Keywords

Tocilizumab; Giant Cell Arteritis; ACTEMRA(R)

Outcome Measures

Primary Outcomes (1)

• 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

  Through Month 18

Secondary Outcomes (12)

• Time to disease relapse

  Through Month 30

• Number of disease relapses

  At Months 18 and 30

• Annualized relapse rate

  At Months 18 and 30

• Cumulative prednisone (or equivalent) dose

  At Months 18 and 30

• Cumulative Glucocorticoid Toxicity Index (GTI) excluding the bone density domain

  At Months 18 and 30

Study Arms (2)

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

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.

Drug: Discontinue Tocilizumab

Interventions

Tocilizumab DRUG

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

Also known as: ACTEMRA

Tocilizumab Step-Down Dosing Arm

Discontinue Tocilizumab DRUG

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.

Also known as: ACTEMRA

Tocilizumab Withdrawal Arm

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. AND at least one of the following:
• i. 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)
• ii. Symptoms of polymyalgia rheumatica (PMR), defined as shoulder and / or hip girdle pain associated with inflammatory morning stiffness
• b. AND at least one of the following:
• i. Artery biopsy revealing features of GCA (e.g., mononuclear cell infiltration or granulomatous inflammation)
• ii. 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)
• iii. 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

You may not qualify if:

• 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 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

Emory University School of Medicine: Division of Rheumatology

Atlanta, Georgia, 30307, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Johns Hopkins Hospital: Division of Rheumatology Vasculitis Center

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases

Boston, Massachusetts, 02114, United States

RECRUITING

Northwell Health: Division of Rheumatology and Allergy-Clinical Immunology

Great Neck, New York, 11021, United States

RECRUITING

Hospital for Special Surgery, New York: Division of Rheumatology

New York, New York, 10021, United States

NOT YET RECRUITING

University of Pittsburgh Medical Center: Division of Rheumatology and Clinical Immunology

Pittsburgh, Pennsylvania, 15217, United States

RECRUITING

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Sebastian H Unizony, M.D.

  Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2025
• First Posted: August 7, 2025
• Study Start: December 11, 2025
• Primary Completion (Estimated): June 11, 2027
• Study Completion (Estimated): January 11, 2030
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access

Locations

US (7)