CDI Trial on Hold as FDA Probes SARS-CoV-2 Safety Protocols

The maker of an investigational therapy for recurrent C. difficile infection (CDI) says it has paused a phase 3 trial of its donor-derived microbiome pill after receiving a clinical hold letter from the Food and Drug Administration (FDA).

Massachusetts-based Finch Therapeutics Group Inc., said the FDA ordered it to pause enrollment in its trial of PRISM4, a phase-3 trial of the investigational drug CP101, while the agency reviews additional information about the company’s SARS-CoV-2 screening protocols. The letter follows Fitch’s acquisition last year of some manufacturing assets of its former contract manufacturer.

CP101 leverages the growing science around the gut microbiome and its impact on human health and infection control. The therapy is based on delivery of intact microbiome communities harvested from donors with healthy, diverse microbiomes. The resulting pill is designed to release at the appropriate location in the recipient's gastrointestinal tract, thus leading to a restoration of a healthy microbiome in the recipient. The theory is that eliminating gut dysbiosis will help prevent CDI recurrence.

In June 2020, the company announced positive results from its phase 2 trial of the therapy. In that trial, three-quarters of patients with recurrent CDI sustained a clinical cure for 8 weeks after taking just one dose of the pill. By comparison, 61.5% of patients in a standard-therapy control group achieved the same outcome.

Last November, the company published results of an extension phase-2 trial, which included some patients from the original phase-2 study, along with new enrollees. In that trial, 80.3% of patients had sustained clinical cure at 8 weeks, and 78.8% of participants still had a sustained clinical cure at 24 weeks.

The company announced it had begun enrolling patients in PRISM4 at the same time as the extension trial results were announced. However, by that time the FDA had already taken action designed to ensure that microbiome-based therapies like CP101 could not incidentally transmit SARS-CoV-2.

In its press release announcing the clinical hold, Finch explained that it previously used a contract manufacturer called OpenBiome. In March 2020, the FDA put a partial clinical hold on OpenBiome so that the company could implement SARS-CoV-2 testing protocols on its microbiota samples. The following January, OpenBiome was released from the hold after implementing a direct SARS-CoV-2 testing method.

In March 2021, Finch acquired manufacturing assets from OpenBiome, and last November Finch began dosing participants in PRISM4, using samples that had been screened for the novel coronavirus, the company said.

Finch said their screening was the same method used by OpenBiome. Still, earlier this year, the FDA began inquiring for additional information about Finch’s screening protocols. On Feb. 24, the agency issued a clinical hold, which the company said will remain in effect until the FDA is satisfied that the screening protocols are sufficient.

However, Finch also disclosed that a number of participants in the trial did receive doses of CP101 while the hold was in effect. In its press release, the company said it was “conducting a review of the matter.” Through a spokesperson, Finch declined further comment.

The information sought by the FDA includes data related to how samples are shipped to the vendor that performs the SARS-CoV-2 testing and how inconclusive test results are handled, Finch said. No adverse clinical outcomes have been reported in any of Finch’s trials of the drug, the company added.

It is not clear exactly how long the hold might last, nor how the hold might affect the trial.

“Finch is evaluating what impact, if any, the clinical hold may have on the timing of the expected readout of topline data from the PRISM4 trial,” the company said.