Abatacept for Patients With Inflammatory Arthritis Associated With Sjögren's Syndrome: an Open-Label Phase II Study

January 5, 2017 updated by: The Cleveland Clinic
The primary purpose of this pilot study is to evaluate the efficacy and safety of Abatacept in subjects with Sjogren's Syndrome (SS). This clinical trial study will enroll and treat 15 subjects with active moderate and severe inflammatory arthritis associated with primary Sjogren's syndrome (pSS) and secondary Sjogren's sybdrine (sSS) with Rheumatoid Arthrits (RA). All subjects will receive Abatacept weekly by Subcutaneous (SC) dosing. Subjects will receive Abatacept by SC injection of 125 mg on day 1 and followed by 125 mg SC weekly thereafter.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Sjogren's Syndrome (SS) is a common systemic autoimmune disease, including primary and secondary form. About 30% of RA are associated with sSS (1) Tumor necrosis factor alpha inhibitors (TNFa-Is) have been tried in this population without success. Abatacept (CTLA4-Ig) is comprised of the ligand-binding domain of CTLA4 plus human immunoglobulin and represents a novel therapeutic costimulation blocker that modulates the signal required for full T cell activation. Studies have shown that activated CD4 T cells play a role in the pathogenesis of SS, indicating Abatacept might be a useful therapeutic intervention in SS. Subjects who are receiving non-biologic immunosuppressive medications consisting of hydroxychloroquine, methotrexate (MTX), sulfasalazine, or leflunomide, at the time of enrollment will remain on these medications without dosage alteration. Efficacy and Safety data will be collected at the time of each clinic visit. The treatment closing date will occur 6 months after enrollment of each subject. Subjects will be followed at 1, 2, 3, 4, 5, and 6 months. Laboratory studies associated with the clinical trial will test potential autoantibody production for systemic autoimmune diseases.

Study Type

Interventional

Phase

  • Phase 2

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
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of Sjogren's Syndrome
  2. Patients are at least 18 years or older
  3. Patients should have either pSS and/or sSS associated with RA, and must have active moderate to severe inflammatory arthritis as defined by painful joint counts (≥5) and swollen joint counts (≥5), or DAS28 scores>3.2.
  4. One non-biologic DMARD will be permitted.
  5. These patients will be willing and able to comply with treatment and follow-up procedures.
  6. These patients will be willing and able to provide written informed consent.
  7. Both women and men of child bearing age must be willing to use an effective means of birth control while receiving treatment throughout participation in this study. Effective contraception methods include abstinence, oral contraceptives (birth control pills), IUD, diaphragm, Norplant, approved hormone injections, condoms, or medical sterilization.

Exclusion Criteria:

  1. Patients will be excluded if they have a concomitant disorder requiring systemic glucocorticoid (GC) therapy (prednisone >10 mg daily or GC equivalent), have organ-threatening features, and have any investigational drug including biologics within 28 days of study entry.
  2. History of cancer or diabetes mellitus
  3. Use of tricyclic antidepressants or anticholinergics
  4. Evidence of active infection or chronic infection including human immunodeficiency virus (HIV), tuberculosis (TB), hepatitis C, or a positive hepatitis B surface antigen.
  5. Patients with latent TB if not treated with isoniazid for at least 4 weeks prior to receiving the study drug
  6. Radiographic evidence of COPD, emphysema, and/or interstitial lung disease.
  7. Subjects who are pregnant or who are nursing infants
  8. Patients with cytopenia: platelet count <80,000/mm3, absolute neutrophil count<1500/mm3, hematocrit < 20%.
  9. Patients with renal insufficiency defined by a serum creatinine of greater than or equal to 2.0 mg/dL or creatinine clearance of less than or equal to 35 ml/min.
  10. Use of illegal drugs.
  11. A live vaccination fewer than 4 weeks before enrollment

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: Abatacept
Abatacept by SC injection of 125 mg weekly for 6 months
Drug: Abatacept
by SC injection of 125 mg weekly for 6 months
Other Names:
  • Orencia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Abatacept in patients with inflammatory arthritis and Sjogren's Syndrome
Time Frame: 6 months
To determine the efficacy for inflammatory arthritis of Abatacept in patients with both pSS and sSS. The primary efficacy endpoint for determining the efficacy is the proportion of patients meeting the ACR 20% improvement criteria at month 6.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increase or change in autoantibody profile
Time Frame: Month 3, 6 and 3 month follow up
A secondary endpoint is to assess autoantibody production as measured by Bioplex2200, including antinuclear antibodies (ANA), anti-ENA (Sm, RNP, SSA, SSB, chromatin, Scl70 and centromere) antibodies, anti-dsDNA antibodies, Complement 3 (C3)/Complement 4 (C4), immunoglobulin (Ig), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
Month 3, 6 and 3 month follow up
Explore the potential efficacy of Abatacept in the exocrine glandular function
Time Frame: Month 1, 3 and 6
The last efficacy endpoint is to explore the efficacy of Abatacept in the exocrine glandular function including assessment of xerophthalmia and xerostomia using 0-100 mm visual analog scale (VAS)(29) and functional measurement of salivary gland and lacrimal gland.
Month 1, 3 and 6

Collaborators and Investigators

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

Sponsor

The Cleveland Clinic

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Qingping Yao, MD, Ph.D, The Cleveland Clinic

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

November 1, 2013

Primary Completion (ACTUAL)

October 1, 2014

Study Completion (ACTUAL)

October 1, 2014

Study Registration Dates

First Submitted

November 18, 2013

First Submitted That Met QC Criteria

January 2, 2014

First Posted (ESTIMATE)

January 6, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

January 9, 2017

Last Update Submitted That Met QC Criteria

January 5, 2017

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CC-Yao-2012001

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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