AbatacepT foR ImmUne Checkpoint Inhibitor Associated Myocarditis (ATRIUM): A Phase 3, Investigator-Initiated, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept in ICI Myocarditis

Status: Recruiting
Location: See all (31) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) prior to any study-related procedure being performed. If a participant is unable to provide informed consent due to his/her medical condition, the participant's legally authorized representative may consent on behalf of the study participant, as permitted by local law and institutional Standard Operating Procedures;

• Aged greater than or equal to 18 years at the time of informed consent;

• Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis), alone or in combination with other cancer therapies (i.e. chemotherapy, radiation therapy or targeted therapy). The FDA-approved ICI could be given as part of a clinical trial but not in combination with a new investigational agent which may cause myocarditis;

• A diagnosis of myocarditis.

• Hospitalized at the time of randomization;

• On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug;

• Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial injury will be defined as an institutional troponin (either conventional or high-sensitivity troponin I or T, using the standard institutional assay) with a value that is ≥5 times the upper limit of the reference standard normal for that institution. The troponin assay may be adjusted based on sex depending on institutional standards. This value of troponin of ≥5 times above the institutional upper limits of normal value must be noted within 10 days prior to potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that on one occasion was ≥5 times the upper limits of institutional normal in the 10-day window prior to potential randomization (whether in the inpatient or outpatient setting), but later decreases below that threshold, typically due to starting corticosteroids, would still be considered eligible;

• The following laboratory parameters, not older than 48 hours at the time of randomization, and measured as part of usual care:

‣ Total white blood cell (WBC) count \>2,500/μl

⁃ Absolute neutrophil count (ANC) \>1,500/μL

⁃ Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \<20 times the upper limit of the institutional normal ranges;

• Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test prior to randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug. Participating men must also be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug; and

⁃ Must be willing and able to abide by all study requirements and restrictions.

Locations
United States
California
Cedars-Sinai Medical Center
RECRUITING
Los Angeles
University of California Los Angeles
RECRUITING
Los Angeles
Washington, D.c.
MedStar Health Research Institute, Georgetown University
RECRUITING
Washington D.c.
Florida
Moffitt Cancer Center
RECRUITING
Tampa
Illinois
University of Chicago
RECRUITING
Chicago
Indiana
Franciscan Health
RECRUITING
Indianapolis
Kansas
University of Kansas Medical Center
RECRUITING
Kansas City
Kentucky
University of Kentucky
RECRUITING
Lexington
Massachusetts
Beth Israel Deaconess Medical Center
RECRUITING
Boston
Boston Medical Center
RECRUITING
Boston
Brigham and Women's Hospital
RECRUITING
Boston
Massachusetts General Hospital
RECRUITING
Boston
Maryland
Johns Hopkins
RECRUITING
Baltimore
Maine
Maine Health
RECRUITING
Portland
Michigan
University of Michigan
RECRUITING
Ann Arbor
Minnesota
Mayo Clinic
RECRUITING
Rochester
North Carolina
University of North Carolina Chapel Hill
RECRUITING
Chapel Hill
New Jersey
Robert Wood Johnson University Hospital
RECRUITING
New Brunswick
New York
Columbia University Irving Medical Center
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Ohio
Cleveland Clinic
RECRUITING
Cleveland
Pennsylvania
Lehigh Valley Health Network
RECRUITING
Bethlehem
University of Pennsylvania
RECRUITING
Philadelphia
Allegheny-Singer Research Institution
RECRUITING
Pittsburgh
Texas
University of Texas Southwestern
RECRUITING
Dallas
MD Anderson Cancer Center
NOT_YET_RECRUITING
Houston
Utah
University of Utah
RECRUITING
Salt Lake City
Wisconsin
Aurora St Luke's Medical Center
RECRUITING
Milwaukee
West Virginia
University of West Virginia
RECRUITING
Morgantown
Other Locations
Canada
McMaster University
RECRUITING
Hamilton
University of British Colombia
RECRUITING
Vancouver
Contact Information
Primary
Hannah K Gilman, MS
hkgilman@mgh.harvard.edu
6177261019
Time Frame
Start Date: 2022-07-02
Estimated Completion Date: 2027-04-20
Participants
Target number of participants: 390
Treatments
Experimental: Abatacept plus standard of care
Abatacept (10 mg/kg) will be administered IV after randomization, again at 24 hours after first study drug treatment, at 14 days after first study drug treatment and an optional 4th dose at 28 days.
Placebo_comparator: Placebo plus standard of care
Placebo will be administered at the same intervals.
Sponsors
Collaborators: Bristol-Myers Squibb
Leads: Massachusetts General Hospital

This content was sourced from clinicaltrials.gov