Stopping versus reducing tocilizumab for people with well-controlled giant cell arteritis

A Randomized Study of Tocilizumab Discontinuation for Patients With Giant Cell Arteritis in Remission (AGA01)

This trial will test whether stopping tocilizumab or reducing its dose better maintains remission in people with giant cell arteritis who have been on high-dose tocilizumab for at least 12 months and off steroids for at least three months.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Drugs / interventions: adalimumab, infliximab, certolizumab, golimumab, sarilumab, rituximab, secukinumab, Tocilizumab, Methotrexate, prednisone
• Locations: 7 sites (Atlanta, Georgia and 6 other locations)
• Trial ID: NCT07108387 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, open-label Phase 2 trial comparing continued/step-down dosing versus withdrawal of tocilizumab (ACTEMRA or an FDA-approved biosimilar) in patients with giant cell arteritis who are in remission after at least 12 months of high-dose therapy. Eligible participants must have stopped glucocorticoids at least three months before randomization. The trial includes a screening phase (up to 42 days) followed by the treatment phase during which participants will be assigned to either discontinue or receive reduced/maintained tocilizumab (given as monthly IV 6–8 mg/kg or weekly 162 mg SC per local practice). Outcomes will focus on safety and the duration of maintained remission after dose change or withdrawal.

Who should consider this trial

Good fit: Adults with giant cell arteritis who have been in remission for at least 12 months on high-dose tocilizumab and have been off glucocorticoids for at least three months are ideal candidates.

Not a fit: Patients with active or recently relapsing GCA, those who have not completed at least 12 months of high-dose tocilizumab, those still on glucocorticoids within three months, or people with contraindications to tocilizumab are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the trial could show that some patients can safely stop or reduce tocilizumab, lowering medication burden, cost, and potential adverse effects while keeping disease under control.

How similar studies have performed: Previous trials have shown tocilizumab is effective for inducing and maintaining remission and sparing steroids in GCA, but the best duration and stopping strategy remains unclear, so this approach is supported by prior efficacy data but not yet settled.

Eligibility criteria

Inclusion Criteria:

1. Ability and willingness to provide written informed consent and to comply with the study protocol
2. 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
3. Glucocorticoid-free remission on Tacrolimus (TCZ) therapy according to the following criteria:

   1. 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
   2. 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
   3. Absence of oral, IV, intramuscular (IM), or SC glucocorticoid treatment for at least 3 months prior to randomization

Exclusion Criteria:

1. 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)
2. Hospitalization within 8 weeks prior to randomization
3. Suspected or established adrenal insufficiency
4. Treatment with any investigational agent within 12 months of randomization
5. 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
6. Immunization with a live/attenuated vaccine within \<= 4 weeks prior to randomization
7. History of severe allergic or anaphylactic reactions to Tocilizumab (TCZ) or to prednisone (or equivalent)
8. 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
9. Serologic evidence of chronic hepatitis infection at time of TCZ initiation or at screening if not previously assessed:

   1. 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
   2. 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
10. Positive interferon gamma release assay (IGRA) (e.g., QuantiFERON Gold or equivalent) at time of TCZ initiation or at screening if not previously assessed

    1. 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
    2. Participants diagnosed with latent TB are eligible but must have initiated appropriate prophylaxis for at least 30 days prior to initiation of study treatment
    3. 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.
11. Known active bacterial, viral, fungal, mycobacterial, or other infections except fungal infections of the nail beds and superficial cutaneous infection treated topically
12. Participant is pregnant or breastfeeding or planning a pregnancy while enrolled in the study
13. Any infection requiring treatment with IV antibiotics within 4 weeks of randomization or oral antibiotics within 2 weeks of randomization
14. Active treatment for malignancy at the time of randomization, with exception of prophylactic hormonal therapy (e.g. prostate cancer, breast cancer, etc.)
15. History of alcohol, drug, or chemical abuse within 12 months prior to randomization
16. History of chronic or recurrent infection (excluding simple cystitis, viral respiratory infection, sinusitis, dermatophyte (tinea) infection) within 12 months prior to randomization
17. History of opportunistic infection within 12 months prior to randomization unless evaluated and cleared by an infectious disease or pulmonary specialist
18. Any of the following laboratory values during screening:

    1. Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) \> 1.5 × upper limit of normal (ULN)
    2. Platelet count \< 100 × 10\^9/L (100,000/mm\^3)
    3. Hemoglobin (Hb) \< 90 g/L (9 g/dL; 5.6 mmol/L)
    4. White blood cells \< 3.0 × 10\^9/L (3000/mm\^3)
    5. Absolute neutrophil count (ANC) \< 1.0 × 10\^9/L (1000/mm\^3)
19. 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

Where this trial is running

Atlanta, Georgia and 6 other locations

• Emory University School of Medicine: Division of Rheumatology — Atlanta, Georgia, United States (Recruiting)
• Northwestern University — Chicago, Illinois, United States (Not_yet_recruiting)
• Johns Hopkins Hospital: Division of Rheumatology Vasculitis Center — Baltimore, Maryland, United States (Recruiting)
• Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases — Boston, Massachusetts, United States (Recruiting)
• Northwell Health: Division of Rheumatology and Allergy-Clinical Immunology — Great Neck, New York, United States (Recruiting)
• Hospital for Special Surgery, New York: Division of Rheumatology — New York, New York, United States (Not_yet_recruiting)
• University of Pittsburgh Medical Center: Division of Rheumatology and Clinical Immunology — Pittsburgh, Pennsylvania, United States (Recruiting)

Conditions Giant Cell Arteritis; Tocilizumab; ACTEMRA