Carmell Therapeutics Corp., of Pittsburgh, received fast track designation from the U.S. FDA for its first product, CT-101, a bone healing accelerant. Carmell is gearing up for a phase III study of the plasma-based bioactive accelerant as part of its pursuit of a biologic license application.

A phase II study showed that the accelerant enabled 36% more patients with compound or open tibia fractures to bear weight and heal the break at six months than standard care. Patients who had the accelerant also developed fewer infections and showed more advanced healing at 30 days.

“Carmell Therapeutics is now on a path to be the first company in the bone healing space with a BLA supported by two prospective, randomized, multicenter clinical studies demonstrating superiority to the current standard of care,” said Donna Godward, Carmell’s chief quality officer.

The FDA cleared the investigational new drug application for the product in December 2019.

“[T]his fast track designation allows for a rolling review for our Biologic License Application (BLA), which means that Carmell can submit sections of our BLA package for review by FDA as they are completed, rather than waiting until the entire application is complete as is usually required. This rolling review process allows for a significantly shorter period for approval after clinical trial completion,” said Stephanie Kladakis, Carmell’s chief scientific officer.

“In general, we believe the rolling review will provide a six- to 18-month positive impact for us,” Carmell CEO Randy Hubbell told BioWorld. The company plans to submit the chemical manufacturing and controls component of the BLA first and then follow up with the results from the clinical trial.

The shortened timeline is particularly welcome with the disruptions from COVID-19. “We had expected to enroll the first patient in July. Now the date’s to be determined, based off the COVID effect,” Hubbell said. “If I had to guess, I’d say we’d start [the trial] in the fourth quarter. Overall, we expect COVID to have a four- to six-month impact on enrollment.”

Phase III trial

Hubbell expects the phase III trial to take 18 months to enroll all patients. While the study’s primary endpoint is assessed at six months, all patients will be monitored for 12 months total. The company anticipates submitting the clinical package within a month of the end of the 12-month monitoring period for the last patient.

While the time the FDA takes to review applications varies considerably, “we expect about a six-month turnaround based on the fast track approval,” Hubbell noted. As previous studies have raised no safety signals, Hubbell expects the approval process to be “very straightforward.”

The trial has an adaptive study design, initially targeted for 220 participants with a 20-point treatment effect, Hubbell explained. “If we see a higher than 20 absolute points difference, we will enroll fewer patients.”

Like the phase II study, the upcoming trial will focus on open tibia fractures, those where the bone protrudes through the skin.

“Once skin is compromised, the healing environment is dramatically negatively impacted,” Hubbell said. “Typically, recovery takes nine to 12 months for that type of severe tibia fracture and up to 8% never achieve union.”

The current standard of care uses fixation with a metal rod inserted in the tibia.

In the company’s trials, all patients receive the current standard of care and patients in the intervention arm have a bone healing accelerant “putty” placed inside crevices and cracks of the bone.

The study will evaluate healing at three, six, and 12 months using X-rays, as well as ability to bear weight, and need for secondary intervention. Reduction in infection rates will be a secondary endpoint.

The product

The bone healing accelerant stimulates bone cells to quickly grow new tissue to repair a fracture using the entire solids content of human blood plasma. The company’s technology enables the safe use of allogenic whole platelet-enriched plasma from healthy volunteers rather than requiring extraction from the patient and maintains bioactivity of critical growth factors.

When combined with beta-tricalcium phosphate (beta-TCP), the plasma-based bioactive materials (PBMs) can be formed into putty, screws, pastes, plugs, or other shapes and are shelf-stable at room temperature. Because the PBMs crosslink plasma with genipin, they can be fine-tuned to release active biologics over a set period of up to two months to continue to stimulate healing, according to Hubbell.

While an accelerant that aids healing in fractures that require plates, screws or rods has a “very, very large market,” Hubbell said, the same technology can also be used in spinal fusions and dental implants, particularly for patients who may have impaired healing, such as individuals with diabetes, obesity, and advanced age and smokers.

A second product, a paste for wound care, is also in development. It is targeted for burn patients as well to reduce scarring and surgical site infection.

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