Baricitinib in Relapsing Giant Cell Arteritis
Condition: Arteritis, Giant Cell
MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
Intervention: Baricitinib
Intervention description: 4 milligrams oral Baricitinib daily for 52 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      This study will evaluate the safety and effectiveness of baricitinib in the treatment of
      giant cell arteritis. All participants will be taking prednisone at the start of the study.
      The prednisone will be reduced according to a standardized tapering schedule while
      participants continue to take one tablet of baricitinib daily for 52 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of Giant Cell Arteritis (GCA) defined by the following Revised GCA Diagnosis
             Criteria:

               -  Age ≥50 years.

               -  History of Erythrocyte Sedimentation Rate (ESR) ≥ 50 mm/hour or C-Reactive
                  Protein (CRP) ≥ 10 mg/L.

               -  Presence of at least one of the following:

                    -  Unequivocal cranial symptoms of GCA (new onset localized headache, scalp or
                       temporal artery tenderness, otherwise unexplained mouth or jaw pain upon
                       mastication).

                    -  Unequivocal symptoms of Polymyalgia Rheumatica (PMR), defined as shoulder
                       and/or hip girdle pain associated with inflammatory stiffness.

                    -  Systemic inflammatory disease in which the presence of the fever (>38
                       degrees Celsius for ≥ 7 days), weight loss (> 5 pounds or 10% premorbid
                       weight), and/or night sweats were attributable to GCA and no other cause was
                       identified.

               -  Presence of at least one of the following:

                    -  Temporal artery biopsy revealing features of GCA.

                    -  Evidence of large-vessel vasculitis by angiography or cross-sectional
                       imaging, including but not limited to magnetic resonance angiography (MRA),
                       computed tomography angiography (CTA), positron emission tomography-computed
                       tomography (PET-CT) or evidence of large-vessel or temporal artery
                       vasculitis by ultrasound (US).

          2. Relapse with active GCA within 6 weeks of study entry where active disease is defined
             by an ESR ≥30 mm/hr or CRP ≥10 mg/L AND the presence of at least one of the following:

               -  Unequivocal cranial symptoms of GCA (new onset or recurrent localized headache,
                  scalp or temporal artery tenderness, otherwise unexplained mouth or jaw pain upon
                  mastication [i.e., jaw claudication]).

               -  Unequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain
                  associated with inflammatory stiffness.

               -  Other feature(s) judged by the clinician investigator to be consistent with GCA
                  or PMR flares (e.g. fever of unknown origin, weight loss, fatigue/malaise, etc.)

          3. Clinically stable at baseline visit (study drug initiation) such that the subject is
             able to safely participate in the standardized taper regimen in the opinion of the
             investigator.

        Exclusion Criteria

          1. Presence of any other autoimmune disease (such as systemic lupus erythematosus,
             rheumatoid arthritis, inflammatory arthritis, other vasculitides, scleroderma,
             polymyositis, dermatomyositis, or other similar systemic connective tissue diseases).

          2. Subjects demonstrating symptoms of visual loss (transient or permanent blindness) or
             diplopia attributable to GCA.

          3. Subjects with history of aortic dissection, myocardial infarction, or cerebrovascular
             attack attributable to GCA.

          4. Has received, or is expected to receive, any live virus vaccinations (with the
             exception of herpes zoster vaccination) within 3 months before the first dose of study
             drug, during the study, or within 3 months after the last administration of the study
             drug. All patients who have not received the herpes zoster vaccine at screening will
             be encouraged (per local guidelines) to do so prior to randomization; vaccination must
             occur >4 weeks prior to randomization and start of investigational product. Patients
             will be excluded if they were exposed to herpes zoster vaccination within 4 weeks of
             planned randomization.

          5. Organ transplant recipients.

          6. Have had a major surgery within 8 weeks prior to screening or will require major
             surgery during the study that, in the opinion of the investigator would pose an
             unacceptable risk to the patient.

          7. Have experienced any of the following within 12 weeks of screening: myocardial
             infarction (MI), unstable ischemic heart disease, stroke, or New York Heart
             Association Stage IV heart failure

          8. Have a history or presence of cardiovascular (including but not limited to
             uncontrolled hypertension), respiratory, hepatic, gastrointestinal, endocrine,
             hematological, neurological, or neuropsychiatric disorders, or any other serious
             and/or unstable illness that, in the opinion of the investigator, could constitute an
             unacceptable risk when taking investigational product or interfere with the
             interpretation of data.

          9. Are largely or wholly incapacitated permitting little or no self-care, such as being
             bedridden or confined to a wheelchair.

         10. Have an estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73 m^².

         11. Have a history of chronic liver disease with the most recent available aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit of
             normal (ULN) or the most recent available total bilirubin ≥1.5 times ULN (if
             available).

         12. Have a history of lymphoproliferative disease; or have signs or symptoms suggestive of
             possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or
             have active primary or recurrent malignant disease; or have been in remission from
             clinically significant malignancy for < 5 years.

               1. Subjects with uterine cervical carcinoma in situ that has been resected with no
                  evidence of recurrence or metastatic disease for at least 3 years may participate
                  in the study

               2. Subjects with basal cell or squamous epithelial skin cancers which have been
                  completely resected with no evidence of recurrence for at least 3 years may
                  participate in the study.

         13. Active infections, or history of recurrent infections or have required management of
             acute or chronic infections as evidenced by any of the following:

               1. Currently on any suppressive therapy for a chronic infection (such as
                  tuberculosis, cytomegalovirus, herpes simplex, herpes zoster, or atypical
                  mycobacteria).

               2. History or suspicion of chronic infection (e.g. prosthetic joint infection)

               3. Hospitalization for treatment of infection within 60 days of baseline visit

               4. Use of parenteral (IV or IM) antimicrobials (antibacterial, antifungals,
                  antivirals, or antiparasitic agents) within 60 days of baseline or oral
                  antimicrobials within 30 days of baseline visit for treatment of an active
                  infection. This does not include the use of antibiotics for prophylaxis against
                  pneumocystis pneumonia since this is considered standard of care for patients on
                  prednisone ≥ 20 mg/day for longer than 3 consecutive months.

         14. Have had symptomatic herpes zoster infection within 12 weeks prior to screening.

         15. Have a history of disseminated/complicated herpes zoster [for example, multidermatomal
             involvement, ophthalmic zoster or Central Nervous System (CNS) involvement]

         16. In the opinion of the investigator, are at an unacceptable risk for participating in
             the study.

         17. Have known or documented diagnosis of human immunodeficiency virus (HIV).

         18. Have known or documented primary immunodeficiency.

         19. Have had household contact with a person with active tuberculosis (TB) and did not
             receive appropriate and documented prophylaxis for TB.

         20. Have had evidence of active TB or have previously had evidence of active TB and did
             not receive appropriate and documented treatment.

         21. Have evidence of latent TB as documented by a local lab positive QuantiFERON®-TB Gold
             test and a normal chest x-ray, unless a patient completes at least 4 weeks of
             appropriate treatment prior to study entry and agrees to complete the remainder of
             treatment while in the trial.

               1. If the QuantiFERON®-TB Gold test results are positive, the patient will be
                  considered to have latent TB and will be excluded. If the test is indeterminate,
                  the test may be repeated once within 2 weeks of the initial value. If the repeat
                  test results are again not negative, the subject will be considered to have
                  latent TB (for purposes of this study) and will be excluded.

               2. Exceptions include subjects with a history of active or latent TB who have
                  documented evidence of appropriate treatment and with no history of re-exposure
                  since their treatment was completed. (Such subjects would not be required to
                  undergo the protocol specific TB testing, but would require a baseline chest
                  x-ray).

         22. Have a positive test for Hepatitis B Virus (HBV) defined as:

               1. Positive for hepatitis B surface antigen (HBsAg), or

               2. Positive for anti-hepatitis B core antibody (HBcAb) If any of the Hepatitis B
                  tests have an indeterminate result, confirmatory testing will be performed by an
                  alternate method.

         23. Have Hepatitis C Virus (HCV) (positive for anti-hepatitis C antibody with confirmed
             presence of HCV).

         24. Have any of the following specific abnormalities on screening tests:

               1. ALT or AST > 2 x ULN

               2. Total bilirubin ≥1.5 x ULN

               3. Hemoglobin < 10 grams/deciliter

               4. Total white blood cell count (WBC) < 2500 cells/μL)

               5. Neutropenia (absolute neutrophil count [ANC] < 1200 cells/μL

               6. Lymphopenia (lymphocyte count < 750 cells/μL)

               7. Thrombocytopenia (platelets < 100,000 cells/μL)

               8. eGFR < 50 mL/min/1.73m²

             In the case of any of the aforementioned laboratory abnormalities, the tests may be
             repeated once within approximately 2 weeks from the initial values, and values
             resulting from repeat testing may be accepted for enrollment eligibility if they meet
             the eligibility criterion.

         25. Are pregnant or breast feeding at the time of screening or enrollment.

         26. Are females of childbearing potential who do not agree to use 2 forms of highly
             effective birth control when engaging in sexual intercourse with a male partner while
             enrolled in the study and for at least 4 weeks following the last dose of the study
             drug

               1. Females of non-childbearing potential are defined as women ≥60 years of age,
                  women

                  ≥40 but <60 years of age what had had cessation of menses for at least 12 months,
                  or whom who are congenitally or surgically sterile (that is have had a
                  hysterectomy, or bilateral oophorectomy or tubal ligation)

               2. The following birth control methods are considered highly effective (the subject
                  should choose 2 to be used with their male partner

             i. Oral, injectable, or implanted hormonal contraceptives ii. Condom with spermicidal
             foam, gel film, cream or suppository iii. Occlusive cap (diaphragm or cervical/vault
             caps) with a spermicidal foam, gel, film, cream or suppository iv. . Intrauterine
             device v. Intrauterine system (for example progestin-releasing coil) vi. Vasectomies
             male (with appropriate post-vasectomy documentation of the absence of sperm in the
             ejaculate)

         27. Are males who do not agree to use 2 forms of highly effective birth control (see
             above) while engaging in sexual intercourse with females partners of childbearing
             potential while enrolled in the study and for 4 weeks after the last dose of the study
             drug.

         28. Have donated more than a single unit of blood within 4 weeks prior to screening or
             intend to donate blood during the course of the study.

         29. Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug above
             within the 2 years prior to screening.

         30. Have previously received baricitinib for other investigational study.

         31. Are unable or unwilling to make themselves available for the duration of the study
             and/or are unwilling to follow study restrictions/procedures

         32. Are currently enrolled in, or discontinued within 4 weeks prior to screening from any
             other clinical trial involving an investigational product or nonapproved use of a drug
             or device or concurrently enrolled in any other type of medical research judged not to
             be scientifically or medically compatible with this study.

         33. Are investigator site personnel directly affiliated with this study and/or their
             immediate families. Immediate family is defined as a spouse, parent, child, or sibling
             whether biological or legally adopted.

         34. Have a chronic medical illness requiring the use of oral of IV glucocorticoid
             treatment (e.g. asthma or emphysema) during the trial or requiring long term
             glucocorticoid treatment such that they would not be able to safely undergone a
             standardized glucocorticoid taper.