The Medicines Company Discontinues Phase 3 CHAMPION Clinical Trial Program of Cangrelor
By C. Michael Gibson, M.S., M.D. For Dr. Gibson's disclosures, please click here. Dr. Gibson served as a member of the Executive and Steering Committees for the CHAMPION trial
CHAMPION Program Discontinued
The phase 3 CHAMPION clinical trial program of the investigational agent cangrelor was discontinued today. The intravenous agent was being evaluated in patients undergoing percutaneous coronary intervention (PCI). The announcement was made by the sponsoring company, The Medicines Company, in a press release.
In consultation with the Drug Safety Monitoring Board, the independent Interim Analysis Review Committee (IARC) told the sponsor that the CHAMPION-PLATFORM trial would "not meet the goal of demonstrating persuasive evidence of clinical effectiveness that could form the basis for regulatory approval. This placebo-controlled trial compared treatment with cangrelor (in combination with usual care) to usual care in patients who require PCI." The IARC indicated that "based on updated information, the CHAMPION-PCI trial, a clinical trial comparing treatment with cangrelor to clopidogrel (600 mg loading dose) in patients who require PCI, showed no significant differences in measures of clinical effectiveness." While there was no increase risk of bleeding compared to clopidogrel, there was an increased risk of minor bleeding in comparison to placebo. The program was not discontinued due to safety concerns.
"Based on the totality of these data, the IARC has recommended that enrollment in both trials be discontinued and that all remaining data should be collected and analyzed." The sponsor is currently notifying investigators and regulatory agencies of the discontinuation of the CHAMPION program.
Clive Meanwell, M.D., Ph.D, Chief Executive Officer of The Medicines Company stated "We are disappointed that the CHAMPION program has not provided sufficient evidence of the clinical effectiveness of cangrelor to warrant completion of these Phase 3 trials. We thank the Investigators and oversight Committees for their work and we will follow their guidance. The trials are being discontinued; we plan to finalize data collection and analyses, and we expect that the data will be presented at a major cardiology meeting in due course. We will now move forward more quickly with our studies where cangrelor is tested to enable safe “bridging” of patients undergoing surgery. In this setting of high unmet medical need, long-term clopidogrel is often discontinued at considerable risk to patients. The rapid onset, offset and titratable anti-platelet pharmacology of cangrelor seems ideally suited for this potential use. The development of cangrelor will therefore continue.”
"The BRIDGE study aims to establish the dosage of cangrelor that achieves ≥60% inhibition of platelet aggregation for five days. The Company plans to enroll approximately 200 patients who discontinue clopidogrel in preparation for cardiac surgery. The aim is to show safe “bridging” of patients during the pre- and post-surgical period of risk. If successful, this approach may form the basis for subsequent regulatory filings."
There were two large studies that constituted the phase 3 program for cangrelor, both of which were nearly completed at the time the program was discontinued:
The CHAMPION-PCI Trial
The goal of this trial was to demonstrate that the efficacy of cangrelor is superior, or at least non-inferior, to that of clopidogrel in subjects requiring PCI. The primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), and ischemia driven revascularization (IDR) at 48 hours after PCI. This trial enrolled 98% of the patients out of a planned target of 9,000 patients.
The CHAMPION-PLATFORM Trial
The goal of this study was to demonstrate that cangrelor is superior to that of usual care, in subjects requiring PCI. The primary endpoint was all-cause mortality, MI, and IDR. This trial enrolled 83% of the planned target of 6,400 patients.
Slides
Click on the links below, and you will be directed to another page, then click on the link at the top of the next page to download the slides:
Background and Overview of CHAMPION: File:CHAMPION Overview.ppt
CHAMPION Design Slides: File:CHAMPION design slides.ppt
References
The Medicines Company press release dated 5/13/09