Clinical trial: Abatacept for the Treatment of Giant Cell Arteritis (NCT04474847)

Eligibility criteria:
Inclusion Criteria:

          1. A diagnosis of newly diagnosed or relapsing GCA. Diagnostic criteria for GCA

             A patient will be said to have GCA by meeting 3 of 5 of the following modified ACR
             criteria for the classification of GCA in which 1 of the 3 must consist of criteria 4
             or 5:

               1. Age at disease onset ≥ 50 years.

               2. New onset or new type of localized pain in the head.

               3. ESR of > 40 mm in the first hour by the Westergren method or CRP measurement
                  above the laboratory normal limit.

               4. Temporal artery abnormality (i.e., temporal artery tenderness to palpation or
                  decreased pulsation, unrelated to arteriosclerosis of cervical arteries).

               5. Temporal artery or large vessel biopsy showing vasculitis characterized by a
                  predominance of mononuclear cell infiltration or granulomatous inflammation,
                  usually with multinucleated giant cell or an abnormal temporal artery ultrasound
                  showing features consistent with active giant cell arteritis ("halo sign") or
                  characteristic changes of large vessel stenosis or aneurysm by arteriography.

          2. GCA with evidence of active disease (defined below) present within the past 8 weeks.

          3. They must be willing and able to comply with treatment and follow-up procedures.

          4. Both women and men who are of child-bearing potential must be willing to use an
             effective means of birth control while receiving treatment through this study.
             Effective contraception methods include abstinence, surgical sterilization of either
             partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal
             contraception.

          5. They must be willing and able to provide written informed consent.

        Exclusion Criteria:

          1. Evidence of a recent acute infection defined as:

               -  Any acute infection within 60 days prior to randomization that required
                  hospitalization or treatment with parenteral antibiotics.

               -  Any acute infection within 30 days prior to randomization that required oral
                  antimicrobial or antiviral therapy.

          2. Patients with history of chronic or recurrent bacterial infection (such as chronic
             pyelonephritis, osteomyelitis, and bronchiectasis etc.).

          3. Patients with a history of recurrent herpes zoster (more than 1 episode) or
             disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or
             ophthalmic zoster. Symptoms of herpes zoster or herpes simplex must have resolved more
             than 60 days prior to screening.

          4. Patients with a history of systemic fungal infections (such as histoplasmosis,
             blastomycosis, or coccidiomycosis).

          5. Patients with a history of primary immunodeficiency.

          6. Patients at risk for tuberculosis (TB) defined as follows:

               -  Current clinical, radiographic or laboratory evidence of active TB, even if
                  currently being treated. Chest x-rays (posterior/anterior and lateral) obtained
                  within the 6 months prior to screening and TB testing (IFN-gamma release assay or
                  PPD) performed in the past month prior to screening will be accepted; however, a
                  copy of the reports must be placed in the participant binder.

               -  A history of active TB unless there is documentation that the patient had
                  received prior anti-TB treatment that was appropriate in duration and type
                  according to local health authority guidelines.

               -  Patients with a positive TB screening test indicative of latent TB will not be
                  eligible for the study unless they:

                  i. Have no evidence of current TB based on chest x-ray performed during the
                  screening period and by history and physical exam, and ii. They are currently
                  being treated for latent TB or the site has documentation of successful prior
                  treatment of latent TB. Treatment regimens should be dictated by local guidelines
                  as long as the treatment dose and duration meet or exceed local health authority
                  guidelines. If permitted by local guidelines regarding treatment with biologic
                  medications, patients with latent TB may be randomized prior to completion of
                  treatment as long as they have completed at least 4 weeks of treatment and they
                  have no evidence of current TB on chest x-ray at screening.

          7. Patients who are pregnant or who are nursing infants.

          8. Inability to comply with study guidelines.

          9. Cytopenia: platelet count <80,000/mm3, total White Blood Count (WBC) < 3,000/mm3 (3 x
             109/L) absolute neutrophil <1500/mm3, hematocrit < 20%.

         10. Renal insufficiency defined by a creatinine clearance of less than or equal to 20
             ml/min.

         11. AST or ALT > 3 times above normal laboratory range.

         12. Other severe, progressive, or uncontrolled disease that in the investigator's opinion
             could prevent a patient from fulfilling the study requirements or that would increase
             the risk of study participation.

         13. Patients who have a present malignancy or previous malignancy within the last 5 years
             prior to screening (except documented history of cured non-metastatic squamous or
             basal cell skin carcinoma or cervical carcinoma in situ). Patients who had a screening
             procedure that is suspicious for malignancy, and in whom the possibility of malignancy
             cannot be reasonably excluded following additional clinical, laboratory or other
             diagnostic evaluations.

         14. Receipt of an investigational agent or device within 30 days prior to enrollment.

         15. A live vaccination within 3 months before randomization.

         16. Patients on non-biologic immunosuppressants must discontinue these medications before
             randomization (azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide,
             hydroxychloroquine, cyclosporin, tacrolimus, or other conventional immunosuppressive
             agent).

         17. Patients who had received an alkylating agent such as cyclophosphamide must
             discontinue these medications at least 8 weeks before randomization.

         18. Patients who have been treated within 4 weeks of randomization with etanercept or
             within 8 weeks with adalimumab, certolizumab, golimumab, or infliximab.

         19. Patients who have been treated within 8 weeks of randomization with anti-IL-6 agents
             (e.g., tocilizumab, sirukumab) or a janus kinase inhibitor.

         20. Patients who have been treated within 4 weeks of randomization with anakinra.

         21. Patients who have received prior treatment with rituximab within the past 6 months
             prior to randomization.

         22. Patients who have received prior treatment with abatacept or CTLA4-Ig.

         23. Patients who will require oral or IV glucocorticoid treatment during the trial for
             conditions other than GCA.

         24. Hypersensitivity to abatacept and/or its excipients.

         25. Presence of any of the following disease processes:

               -  Takayasu arteritis

               -  Granulomatosis with polyangiitis

               -  Microscopic polyangiitis

               -  Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

               -  Polyarteritis nodosa

               -  Cogan's syndrome

               -  Behçet's disease

               -  Sarcoidosis

               -  Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics
                  vasculitis

               -  Cryoglobulinemic vasculitis

               -  Systemic lupus erythematosus

               -  Rheumatoid arthritis

               -  Mixed connective tissue disease or any overlap autoimmune syndrome
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.


Patient description (medical language): A 61-year-old man comes to the emergency department complaining of an acute vision disturbance. He had an episode of vision disturbance in the right eye that occurred suddenly and resolved spontaneously in 15 minutes. He also has right jaw pain while chewing.  He also complains of fatigue and hip muscle aches over the last several months.  The patient has a history of mild hyperlipidemia that has been controlled by diet and lifestyle modifications.  On examination, his blood pressure is 130/70 mm Hg and pulse is 66/min.  Neurological examination is unremarkable.  Visual examination is also normal. ESR is 103 mm/h. Temporal artery biopsy shows multinuclear giant cells and internal elastic membrane fragmentation.

Patient description (patient's own words): I’m a 61-year-old man and I came to the ER because I had a sudden episode where I couldn’t see out of my right eye. It only lasted about 15 minutes and went away on its own but it really scared me. I’ve also been having pain in my right jaw when I chew. For the past few months I’ve felt really tired and noticed my hips ache a lot. I have a history of mild cholesterol issues but I’ve been managing that with my diet and lifestyle. When the doctors checked me my blood pressure and pulse were normal and my vision and neurological exams didn’t show anything wrong. However they ran some tests and said my ESR levels were very high and a biopsy of my temporal artery showed some inflammation and damage.

Does the patient match the trial criteria? Entailment