Abatacept for the Treatment of Myositis-associated Interstitial Lung Disease (ATtackMy-ILD)

May 30, 2023 updated by: Rohit Aggarwal, MD

A Randomized, Controlled Pilot Trial to Evaluate the Efficacy and Safety of Subcutaneous Abatacept in Treating Interstitial Lung Disease Associated With the Anti-synthetase Syndrome

A randomized, controlled pilot trial to evaluate the efficacy and safety of subcutaneous Abatacept in treating interstitial lung disease associated with the anti-synthetase syndrome.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a proof of concept study to evaluate the efficacy, safety and tolerability of abatacept in Syn-ILD in a multi-center randomized, placebo-controlled 6-month (24-week) pilot study.

Study Type

Interventional

Enrollment (Actual)

20

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
    • California
      • Beverly Hills, California, United States, 90211
        • Cedars-Sinai Medical Center
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • John Hopkins Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham & Women's Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

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

Description

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Anti-synthetase syndrome defined as the patient possessing 1 antisynthetase autoantibody (Jo-1, PL-12, PL-7, KS, OJ, EJ, Zo) in the presence of autoimmune ILD.
  3. ILD defined by radiographic (HRCT chest) findings of reticulation, honeycombing or ground glass opacities (GGO) without another plausible explanation. HRCT chest defining ILD for inclusion criteria, should be within last 1 year done as SOC.
  4. Active ILD (see Section 4.2).
  5. Baseline FVC a) % <80% b) FVC 80-100% with > = 10% decline in FVC in last 12 months as minimal threshold of ILD severity (PFT done within last 3 months is acceptable for inclusion criteria determination)

  6. SOC immunosuppressive therapy (IS) therapy:

    1. Steroids (prednisone or other forms of steroid in equivalent doses) OR one of the other immunosuppressive agent (either Mycophenolate (MMF) or Azathioprine (AZA) OR a combination of steroid and an immunosuppressive agent. MMF (maximum of 3 gm/day) or azathioprine (maximum of 200 mg/day).Goal is to start the trial drug (or placebo) soon after starting SOC (MMF/AZA/Steroids) and their doses are stable. Note that patients on steroids alone as well as not on steroids can be enrolled in the trial as well.
    2. Desired dose of the SOC therapy should be reached 4 weeks prior to first study visit (Visit 1). No dose changes are allowed 4 weeks prior to first study visit.
    3. Dose of concomitant therapy (SOC) cannot be changed during the 24 weeks of the trial unless safety/toxicity issues supervene.
    4. If on steroid, the steroid dose must be stable for 2 weeks prior to Visit 1.
  7. No other concomitant IS medications including methotrexate, cyclosporine, intravenous immunoglobulin (IVIG), tacrolimus, cyclophosphamide or tofacitinib.
  8. No concomitant biologic agents (i.e. rituximab, anti-tumor necrosis factor (TNF) agents, tocilizumab).
  9. Additional IS therapy: Patient cannot begin any new IS therapy or new steroid taper for the 24-week study period, except if severe clinical worsening (flare up) of the disease requiring rescue therapy occurs (i.e. documentation of worsening of PFT/HRCT and patient and physician determination of worsening). See section of rescue medication below for details.

  10. If the enrolling physician is planning to discontinue current IS agent or steroid before clinical trial, then following washout period is required prior to Visit 1.

    Medication Washout Period methotrexate 4 weeks Other IS agent (e.g. azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) 4 weeks IVIg or cyclophosphamide 3 months rituximab 6 months infliximab or adalimumab 8 weeks glucocorticoids 2 weeks etanercept 2 weeks anakinra 1 week pirfenidone 4 weeks

  11. Men and women of reproductive potential must agree to use an acceptable method of birth control during the trial period.
  12. Subject has provided written informed consent.

Exclusion Criteria:

A patient will be excluded if any of the following Exclusion Criteria are met:

  1. Severe end stage lung disease:

    1. FVC ≤30% or Forced expiratory volume (FEV1) ≤ 30% or
    2. Requirement of high O2 requirement ≥ 6 L/min at rest for >1 month before the study enrollment or
    3. Listed for lung transplantation or
    4. PI feels that ILD is severe and end stage fibrosis is such that there is low potential for improvement with any disease modifying intervention.
  2. Subjects under the age of 18.
  3. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
  4. Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening.
  5. Active tuberculosis (TB) requiring treatment within the previous 3 years. Patients should be screened for latent TB using purified protein derivative (PPD)/or quantiferon gold within last 1 year and, if positive, treated following local practice guidelines prior to initiating abatacept (ABT). Patients treated for active tuberculosis with no recurrence in 3 years are permitted.
  6. Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
  7. Pregnant women or nursing (breast feeding) mothers.
  8. History of alcohol, drug or chemical abuse within 1 year prior to screening or any medical condition or physical or psychological state that the PI feels would not allow the subject to safely complete the study.
  9. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
  10. Treatment with any other investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening.
  11. Previous treatment with the following cell-depleting therapies, including investigational agents or approved therapies: CAMPATH, anti-CD4, anti-CD5, and anti-CD3.
  12. Previous treatment with ABT.
  13. History of severe allergic or anaphylactic reactions to monoclonal antibodies.
  14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)
  15. Evidence of concomitant lung disease which PI feels may interfere with clinical assessment of ILD for example severe active chronic obstructive pulmonary disease (COPD), asthma, occupational lung disease, pulmonary sarcoidosis, etc.
  16. Prisoners or subjects who are compulsory detained

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Subcutaneous placebo injection weekly for 24 weeks.
Other: Placebo
Placebo
Experimental: Abatacept
Subcutaneous injection of abatacept 125 mg weekly for 24 weeks. 24 week optional follow up phase all subjects receive abatacept 125 mg weekly.
Drug: Abatacept
Abatacept 125mg subcutaneous weekly
Other Names:
  • Orencia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Forced Vital Capacity (FVC)% Change
Time Frame: 24 Weeks
The primary outcome criteria for efficacy will be the FVC% change from the baseline visit to week 24 between the 2 treatment arms (SOC/placebo vs. SOC/Abatacept).
24 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to progression free survival where progression
Time Frame: 24 weeks
The first occurrence of any of the following: death or lung transplant or FVC ≥10% decline or FVC ≥5% decline with diffuse capacity of lung for carbon dioxide (DLCO) ≥15% decline.
24 weeks
Comparison of change in patient reported dyspnea scores
Time Frame: 24 weeks
measured by University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) (range 0-120, higher score is worsening dyspnea).
24 weeks
Time to improvement in FVC% by ≥10
Time Frame: 24 weeks
Comparison of FVC% results from pulmonary function tests from baseline, 3 and 6 months. Improvement is defined as an FVC% change ≥10.
24 weeks

Collaborators and Investigators

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

Sponsor

Rohit Aggarwal, MD

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Rohit Aggarwal, MD, University of Pittsburgh

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)

June 1, 2017

Primary Completion (Actual)

May 30, 2022

Study Completion (Estimated)

July 30, 2023

Study Registration Dates

First Submitted

June 28, 2017

First Submitted That Met QC Criteria

July 10, 2017

First Posted (Actual)

July 12, 2017

Study Record Updates

Last Update Posted (Actual)

June 1, 2023

Last Update Submitted That Met QC Criteria

May 30, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BMS: IM101-657

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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