Abatacept for the Treatment of Myositis-associated Interstitial Lung Disease

NCT03215927 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY19030443BMS: IM101-657
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Myositis; Interstitial Lung Disease

Keywords

ILD

Outcome Measures

Primary Outcomes (1)

• % Predicted Forced Vital Capacity (FVC) Absolute Change

  The primary outcome criteria for efficacy will be the absolute change of % predicted FVC from the baseline visit to week 24 between the 2 treatment arms (SOC/placebo vs. SOC/Abatacept).

  24 Weeks

Secondary Outcomes (3)

• Time to Progression Free Survival

  48 weeks

• Comparison of Change in Patient Reported Dyspnea Scores (University of California San Diego Shortness of Breath Questionnaire)

  24 weeks

• Time to Improvement in % Predicted FVC ≥10%

  48 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subcutaneous placebo injection weekly for 24 weeks.

Other: Placebo

Abatacept

EXPERIMENTAL

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

Interventions

Abatacept DRUG

Abatacept 125mg subcutaneous weekly

Also known as: Orencia

Abatacept

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• 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.
• Active ILD (see Section 4.2).
• SOC immunosuppressive therapy (IS) therapy:
• 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.
• 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.
• Dose of concomitant therapy (SOC) cannot be changed during the 24 weeks of the trial unless safety/toxicity issues supervene.
• If on steroid, the steroid dose must be stable for 2 weeks prior to Visit 1.
• No other concomitant IS medications including methotrexate, cyclosporine, intravenous immunoglobulin (IVIG), tacrolimus, cyclophosphamide or tofacitinib.
• No concomitant biologic agents (i.e. rituximab, anti-tumor necrosis factor (TNF) agents, tocilizumab).
• 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.
• 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
• Men and women of reproductive potential must agree to use an acceptable method of birth control during the trial period.
• Subject has provided written informed consent.

You may not qualify if:

• Severe end stage lung disease:
• FVC ≤30% or Forced expiratory volume (FEV1) ≤ 30% or
• Requirement of high O2 requirement ≥ 6 L/min at rest for \>1 month before the study enrollment or
• Listed for lung transplantation or
• PI feels that ILD is severe and end stage fibrosis is such that there is low potential for improvement with any disease modifying intervention.
• Subjects under the age of 18.
• 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).
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening.
• 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.
• Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
• Pregnant women or nursing (breast feeding) mothers.
• 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.
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
• Treatment with any other investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening.
• Previous treatment with the following cell-depleting therapies, including investigational agents or approved therapies: CAMPATH, anti-CD4, anti-CD5, and anti-CD3.

Sponsors & Collaborators

• Rohit Aggarwal, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

University of Colorado Anschutz Medical Campus

Denver, Colorado, 80045, United States

Location

John Hopkins Medical Center

Baltimore, Maryland, 21205, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (24)

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MeSH Terms

Conditions

Myositis; Lung Diseases, Interstitial

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Rohit Aggarwal
• Organization: University of Pittsburgh

aggarwalr@upmc.edu

4123838123

Study Officials

• Rohit Aggarwal, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the site pharmacist is unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: A 1:1 randomization scheme for abatacept 125 mg vs. placebo as a weekly subcutaneous (SQ) injection for 24 weeks.

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 12, 2017
• Study Start: January 1, 2018
• Primary Completion: May 30, 2022
• Study Completion: July 30, 2023
• Last Updated: January 7, 2025
• Results First Posted: January 7, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)