Ustekinumab for the Treatment of Giant Cell Arteritis (UGCA)

June 10, 2020 updated by: Sebastian H Unizony, MD, Massachusetts General Hospital

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ustekinumab plus prednisone
  1. Ustekinumab: 90 mg of ustekinumab will be administered subcutaneously at baseline, week 4, week 12, week 20, week 28, week 36 and week 44.
  2. 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.
Drug: Prednisone
Prednisone is an anti-inflammatory medication
Drug: Ustekinumab
Ustekinumab is a humanized monoclonal antibody that targets the p40 subunit of IL-12 and IL-23 and inhibits cytokine - cytokine receptor coupling and signaling
Other Names:
  • Stelara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients in Glucocorticoid-free Remission
Time Frame: 52 weeks
The primary study endpoint, prednisone-free remission, was defined as: 1) absence of relapse from the time that remission was achieved through week 52; 2) normalization of ESR (<40 mm/hour) and CRP (<10 mg/L); and, 3) adherence to the protocol prednisone taper.
52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Disease Flare
Time Frame: 52 weeks
Disease relapse was defined as the recurrence of signs or symptoms of GCA (e.g., cranial or PMR) that required treatment intensification, regardless of the ESR and CRP levels.
52 weeks
Cumulative Prednisone Dose
Time Frame: 52 weeks
52 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Number of Participants With at Least One Adverse Event
Time Frame: 52 weeks
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2016

Primary Completion (ACTUAL)

July 25, 2019

Study Completion (ACTUAL)

September 19, 2019

Study Registration Dates

First Submitted

October 31, 2016

First Submitted That Met QC Criteria

November 2, 2016

First Posted (ESTIMATE)

November 4, 2016

Study Record Updates

Last Update Posted (ACTUAL)

June 12, 2020

Last Update Submitted That Met QC Criteria

June 10, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016P000932

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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