Subjectivity of determining response could have led to bias.

Osiris Therapeutics has decided to end the enrollment of more patients in its Phase III trial with Prochymal in Crohn’s disease. It believes that there is a design flaw in the trial resulting in significantly higher than expected placebo response rates.

The decision was made after the trial’s final scheduled interim analysis showed that one of the two Prochymal dose arms had crossed a futility boundary. The dose arm was unlikely to achieve the primary endpoint of remission because of the high placebo response rate. This latest analysis continued to show no serious safety concerns with the therapy and safety was not a factor in the decision to stop enrollment.

The Prochymal Crohn’s program consists of two separate but related double-blinded trials. The first trial evaluates patients’ initial response to two dose levels of Prochymal as compared to placebo. The trial was originally designed to enroll 270 subjects but has now stopped at 210.

The potential trial design flaw may be related to the fact that patients responding to the initial therapy were eligible to participate in a second, longer-term trial evaluating Prochymal as a maintenance therapy. Because the current standard for determining response of Crohn’s patients to therapy is largely subjective, there may have been response bias to meet the eligibility requirements for continuation of therapy in the longer-term maintenance trial, the company explains.

“We will keep the trial blinded and expect a solid data package for use in designing future trials in Crohn’s disease and to bolster Prochymal’s safety database,” says C. Randal Mills, Ph.D. president and CEO of Osiris Therapeutics.

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