Inefficacy

The purpose of this study is to determine whether ustekinumab is effective in the treatment of Giant Cell Arteritis (GCA)

The objective of this study is to evaluate the efficacy and safety of ustekinumab, an interleukin (IL)-12/23 inhibitor, in patients with GCA

Hypothesis IL-12/23 pathway blockade may maintain disease remission in patients with GCA

Specific Aims

• To evaluate the safety and tolerability of ustekinumab administration in 20 patients with GCA
• To evaluate the efficacy of ustekinumab for remission maintenance and glucocorticoid sparing in 20 patients with GCA

Inclusion Criteria: Subjects must meet the following criteria

1. Able and willing to provide written informed consent and to comply with the study protocol

2. Diagnosis of GCA classified according to the following criteria:

   • Age 50 years or older
   • History of erythrosedimentation rate (ESR) ≥ 50 mm/hour or C-reactive protein (CRP) ≥ 10 mg/L

   AND at least one of the following:

   • Cranial symptoms of GCA
   • Symptoms of polymyalgia rheumatica (PMR)

   AND at least one of the following:

   • Temporal artery biopsy revealing features of GCA
   • Evidence of large-vessel vasculitis by angiography or cross-sectional imaging

3. Active new-onset or relapsing active disease

Exclusion Criteria:

1. Allergies: Subjects who have history of previous severe allergic or anaphylactic reaction associated with the administration of monoclonal antibodies or antibody fragments.

2. Systemic infection: Subjects who have an active systemic infection.

3. Serious infection: Subjects who have had serious infections, or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of enrollment.

4. Chronic or recurrent infection: Subjects who have chronic or recurrent bacterial, viral, fungal, mycobacterial, or protozoan infection.

5. Opportunistic infection: Subjects who have, or have had, an opportunistic infection within 6 months prior to enrollment.

6. Subjects who have active hepatitis B or active hepatitis C or a documented history of HIV

7. Latent tuberculosis infection

8. Malignancy

9. Subjects with evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, immunologic, psychiatric or gastrointestinal disease that could interfere with participation in the trial according to the protocol.

10. Subjects with transplanted organs (with the exception of a corneal transplant > 3 months prior to screening)

11. Major surgery within 8 weeks prior to Screening or planned major surgery within 12 months after Baseline

12. Pregnancy

13. The following laboratory abnormalities

    • Hemoglobin < 8 gr/dL
    • Platelets < 100/mm3
    • White blood cell count (WBC) < 3000/mm3
    • Absolute neutrophil count < 2000/mm3
    • Absolute lymphocyte count < 500/mm3
    • Serum creatinine > 1.4 mg/dL in female subjects and > 1.6 mg/dL in male subjects
    • Total bilirubin > 2 mg/dL
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 X upper limit of normal
    • Positive hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibody

14. Prohibited medications:

    • Subjects who received methotrexate (MTX) > 30 mg weekly, azathioprine, mycophenolate mofetil, cyclophosphamide, chlorambucil, tacrolimus, leflunomide, canakinumab, belimumab, abatacept, tocilizumab, secukinumab, infliximab, etanercept, adalimumab, golimumab, or certolizumab within the 3-month period prior to enrollment.
    • Subjects who had treatment with any anti-cluster designation antigen (CD)20 agent (e.g., rituximab) within the 9-month period prior to enrolment
    • Subjects who used any investigational drug within 1 month prior to enrollment or within 5 half-lives of the investigational agent, whichever is longer.
    • Low dose MTX: Patients on < 30 mg of MTX weekly will be eligible for enrollment after a 2-week washout interval before receiving ustekinumab
    • Vaccines: Subjects who received any live virus or bacterial vaccinations other than bacille Calmette-Guerin (BCG) within the 3 months before the first administration of the study agent, or are expected to receive any live virus or live bacterial vaccinations during the study, or up to 3 month after the last administration of ustekinumab are not eligible. Subjects who received BCG vaccines within the 12 months before the first administration of the study agent, or are expected to receive BCG vaccines during the study, or up to 12 month after the last administration of ustekinumab are also not eligible.

60 weeks