Ustekinumab for the Treatment of Giant Cell Arteritis

Brief Title

Ustekinumab for the Treatment of Giant Cell Arteritis

Official Title

Open Label Study to Test the Safety and Efficacy of Ustekinumab in Patients With Giant Cell Arteritis

Brief Summary

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

Detailed Description

      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
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Percentage of Patients in Glucocorticoid-free Remission

Secondary Outcome

 Number of Participants With Disease Flare

Condition

Giant Cell Arteritis

Intervention

Ustekinumab

Study Arms / Comparison Groups

 Ustekinumab plus prednisone
Description:  Ustekinumab: 90 mg of ustekinumab will be administered subcutaneously at baseline, week 4, week 12, week 20, week 28, week 36 and week 44.
Prednisone: All patients will receive a prednisone course tapered according to predefined schedules starting at either 60 mg, 40 mg or 20 mg. The initial dose of prednisone will be chosen by the investigators according to disease severity and comorbid medical conditions. The duration of the prednisone taper will be 6 months in all cases.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

13

Start Date

December 1, 2016

Completion Date

September 19, 2019

Primary Completion Date

July 25, 2019

Eligibility Criteria

        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.
      

Gender

All

Ages

50 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02955147

Organization ID

2016P000932


Responsible Party

Principal Investigator

Study Sponsor

Massachusetts General Hospital


Study Sponsor

, , 


Verification Date

June 2020