BOSTON _ Riding herd on 70 medical centers conducting a controlled clinical trial that enrolls 1,400 patients in a dozen countries is research cardiologist Thomas Schaible's main job. What makes his task possible is an international consortium of nine companies, committees and academic groups that honchos the nuts, bolts, policies and problems of the study nicknamed CAPTURE (chimeric anti-platelet monoclonal antibody therapy in patients with unstable angina refractory to standard medical treatment).

Schaible is director of cardiology at Centocor Inc., of Malvern, Pa. That company created ReoPro, the recombinant anti-platelet monoclonal antibody being tested in the Phase III, pivotal CAPTURE study. He dissected its organizational and scientific anatomy here last week at the International Business Communications' Fifth Invitational Symposium on Clinical Trials.

Schaible titled his hour-long case-study: "Virtual drug development in an international clinical trial setting: 12 countries, 70 sites".

The FDA approved ReoPro in December 1994 for treating angioplasty patients deemed at high risk for experiencing re-closure of their treated coronaries. This makes the drug available to about 30 percent of the 750,000 patients who undergo balloon angioplasty each year in the U.S. and Europe. (See BioWorld Today, April 18, p. 1.)

The CAPTURE study aims to expand this population of unstable angina sufferers "to prevent ischemic complications, before, during and after" the artery- dilating operation. "It's truly a multi-organization trial," Schaible said, "as well as multi-national. Of the 12 countries in the study, 10 are of the European Community, plus Israel and Canada."

He listed three benefits of such international clinical studies: "Establishing a foothold for global commercialization; influencing world-wide opinion leaders; and differences in clinical practices in other countries enabling development of indications that may modify U.S. practices."

On this last point, Schaible pointed out why CAPTURE leaves out the U.S. "One of the reasons," he said, "is the need to treat patients for a 24-hour period. In the U.S., patients who are symptomatic and undergoing elective angioplasty come into the hospital, get diagnosed, then have their procedure the same day. There's not that one day in between."

In Europe," he went on, "this is not the case. Patients may stay in the hospital for several days before their angioplasty," for observation and work-up.

Asked from the floor how the FDA will view Phase III data acquired entirely abroad, Schaible replied, "In designing the study, we have worked closely with the FDA's Center for Biologics Evaluation and Research. They're fully aware of what we're doing."

Meanwhile, Centocor has an even larger ReoPro trial starting in the U.S. Called EPILOG. It will evaluate angioplasty patients at both high and low risk of developing ischemic complications. EPILOG is enrolling 4,800 trial subjects at 80 centers in the U.S. and Canada, and expects to complete the study early in 1997. CAPTURE is due to end the first quarter of `96.

Managerial Consortium Delegates Huge Tasks

Besides Centocor, which sponsored and is directing CAPTURE, that trial's managerial consortium includes commercial companies and ad hoc committees, with varying tasks, Schaible said. Among these are:

Eli Lilly & Co., (Toronto; Indianapolis), Centocor's 50- 50 marketing partner for ReoPro, provides "international entree with regulatory authorities."

* European Cooperative Study Group specializes in conducting cardiology clinical trials.

* G. H. Besselaar & Assoc. (Maidenhead, U.K.; Brussels, Belgium) a contract research organization, monitors and manages trial data until final unblinding of results.

* Bio-Pharm Inc. (Frankfurt, Germany), besides numbering and blinding treatment kits, reports serious adverse events (side effects) to regulatory authorities.

* Cardialysis, B.V. (Rotterdam, Netherlands.), analyzes patient angiograms and electro-cardiograms; coordinates case reviews.

* Academic Medical Center (Amsterdam) assigns patients to treatment, ships kits, oversees safety.

* Clinical Endpoint Committee deals with endpoints, safety, compliance.

* Safety & Efficacy Monitoring Committee (Louvain, Belgium) recommends stopping or modifying trial.

Deborah Cotton, a staff physician on the faculty of Harvard Medical School, and member of the National Task Force for AIDS Drug Development, chaired the session at which Schaible spoke. She told BioWorld Today that "the paramount concern [evoked by Schaible's presentation] is the ability to shorten significantly the time that it took to do this trial, by really investing in a global network. "His `virtual company'," she added, "is really a very targeted team approach by a variety of organizations, including contract research companies, academic medical centers, Centocor itself.

"My sense too," she added, "is that the kind of structure he created will really serve that company into the future in a variety of different studies." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.