Using Tocilizumab with Steroids for Giant Cell Arteritis with Brain Involvement

Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement (ToGiAC)

This study is testing if a combination of tocilizumab and high-dose steroids can help older adults with giant cell arteritis that affects the brain feel better compared to a placebo.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (other)
• Drugs / interventions: tocilizumab, alemtuzumab, infliximab, certolizumab, golimumab, adalimumab, tofacitinib, cyclophosphamide, prednisone
• Locations: 1 site (Paris)
• Trial ID: NCT04888221 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, placebo-controlled trial in France aims to evaluate the efficacy of tocilizumab combined with high-dose steroids in patients over 60 years old suffering from giant cell arteritis (GCA) with neurovascular involvement. The study will enroll 66 participants, assessing their response to treatment over a 24-week period, with regular follow-ups to monitor remission and any adverse effects. Patients will be screened for symptomatic or asymptomatic ischemic events and will receive either the experimental treatment or a placebo, alongside standard stroke treatments as needed.

Who should consider this trial

Good fit: Ideal candidates are individuals over 60 years old diagnosed with giant cell arteritis and neurovascular involvement, either symptomatic or asymptomatic.

Not a fit: Patients with other proven causes of stroke, such as atrial fibrillation or significant carotid stenosis, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve remission rates and reduce the risk of stroke recurrence in patients with giant cell arteritis.

How similar studies have performed: Previous studies have shown the efficacy of tocilizumab as a steroid-sparing agent, indicating potential success for this novel application in GCA.

Eligibility criteria

Inclusion Criteria:

* Age \> 60 years
* Diagnosis of
* GCA (according to ACR criteria or positive temporal artery biopsy) (de novo and/or relapse) And neurovascular involvement:
* Either Ischemic stroke (including TIA) in the vertebro-basilar or carotid territory (symptomatic arterial involvement)
* Either PET uptake of vertebral and/or carotid arteries (extra or intra cranial) and/or angioCT or angioMRI showing arterial involvement consistent with vasculitis (asymptomatic arterial involvement)
* Inclusion should be done
* within 4 weeks after the stroke concerning the "symptomatic" patients
* within 4 weeks after the diagnosis of GCA (or relapse) concerning the patients with asymptomatic neurovascular involvement.
* Within 21 days after starting the corticosteroids
* Signed Informed Consent Form
* Affiliation to social security

Exclusion Criteria:

Exclusion Criteria :

* Other proven cause of stroke: atrial fibrillation, significant atheromatous stenosis of carotid or vertebro-basilar arteries
* Contraindication to and precaution in use of tocilizumab:

  * Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever was longer) of screening
  * Previous treatment with cell-depleting therapies, including investigational agents,including but not limited to Campath (alemtuzumab), anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20
  * Treatment with IV gamma globulin or plasmapheresis within 24 weeks of baseline
  * Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation
  * Previous treatment with TCZ
  * Immunization with a live/attenuated vaccine within 4 weeks prior to baseline or simultaneously with tocilizumab treatment
  * Treatment with hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil (MMF) within 4 weeks of baseline
  * Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab,abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline
  * Previous treatment with tofacitinib
  * Treatment with cyclophosphamide within 24 weeks of baseline
  * 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 disease
  * Current liver disease, as determined by the investigator
  * History of diverticulitis, diverticulosis requiring antibiotic treatment, or 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 and patients treated for latent TB within 3 years were eligible.
  * 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 had been excised and cured)
  * History of alcohol, drug, or chemical abuse within 1 year prior to screening
  * Body weight \>150 kg
  * Serum creatinine \>1.4 mg/dL (124 µmol/L) in female patients and 1.6 mg/dL (141 µmol/L) in male patients
  * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)× 3 Upper limit of normal (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 x109/L (3000/mm3)
  * Absolute neutrophil count \< 2.0 x 109/L (2000/mm3)
  * Absolute lymphocyte count \< 0.5 X 109/L (500/mm3)
  * Positive hepatitis B surface antigen or hepatitis C antibody
  * Contraindication to aspirin, clopidogrel, steroids use, rifampicin and/or isoniazid
  * Major surgery within 8 weeks prior to screening or planned major surgery within 12 months after randomization, except arterial thrombectomy if necessary for ischemic stroke
  * Transplanted organs (except corneal transplant performed more than 3 months prior to screening)
  * Inability to provide informed consent
  * Participation in another interventional research

Where this trial is running

Paris

• Saint Antoine Hospital, Neurology Unit, Assistance Publique-Hôpitaux de Paris — Paris, France (RECRUITING)

Study contacts

• Principal investigator: Sonia ALAMOWITCH, PU-PH — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Sonia ALAMOWITCH, PU-PH

Conditions: Giant Cell Arteritis, Neurovascular Disorder, ischemic complication/ ischemic event, Cerebro-vascular involvement, Steroids, Tocilizumab, Horton's Giant Cell Arteritis, Vascular Diseases