Several of the first cohort patients have had their Cell Pouch implants for over 3 years and no patients have elected to have their implants removed.
A protocol amendment for the clinical trial (NCT03513939) of Sernova’s Cell Pouch System, a medical device with immune protected therapeutic cells under investigation for the treatment of patients with type 1 diabetes (T1D) with hypoglycemia unawareness and a history of severe hypoglycemic episodes, has been approved by the University of Chicago Institutional Review Board with no objections from the FDA, clearing the way for enrollment of the trial’s second cohort.
The Cell Pouch System “forms a natural vascularized tissue environment in the body for long-term survival and function of therapeutic cells”, in this case, insulin-producing islets. In the trial’s first cohort, 6 patients were treated with an 8-channel Cell Pouch. Of these patients, 3 have completed islet transplants and achieved insulin independence, while the treatment regimen for the other 3 patients remains ongoing. Several of the patients have had their Cell Pouch implants for over 3 years and no patients have elected to have their implants removed.
Based on promising interim results, the protocol for the second cohort will involve use of a 10-channel Cell Pouch and a reduction to 90-day intervals between islets transplants from the 180-day intervals used in the first cohort. Sernova will seek to enroll up to 7 patients in the second cohort and announced that it will collaborate with a clinical trial patient recruitment partner to expedite the enrollment process.
“Sernova is committed to developing a potential ‘functional cure’ with the goal of freeing patients from the life-limiting burdens of T1D and dramatically enhancing their quality of life,” Philip Toleikis, president and chief executive officer, Sernova, said in a statement regarding the news. “We are pleased with the positive interim results demonstrating that the Cell Pouch System is well tolerated, reduces or eliminates the frequency of severe hypoglycemic events and continues to contribute to durable insulin independence among patients. Based on our now expanded recruitment activities and efforts, we anticipate implanting multiple patients before the end of 2022. The results from these additional patients will directly contribute to our pivotal T1D trial design...”
The open-label, phase 1/2 clinical trial is open to patients aged 18 years to 65 years with clinical histories compatible with T1D who experienced disease onset at less than 40 years of age, have been insulin-dependent for 5 or more years, and whose sum of age and insulin dependent diabetes duration of is at least 28 years. Participants are required to have absent stimulated c-peptide (<0.3 ng/mL) in response to a mixed meal tolerance test, involvement in intensive diabetes management according to the trial’s definition, at least 1 episode of severe hypoglycemia in the 12 months prior to study enrollment, and reduced awareness of hypoglycemia. Patients with a body mass index greater than 30 kg/m2, an insulin requirement greater than 1.0 IU/kg/day, glycated hemoglobin greater than 13%, systolic blood pressure greater than 160 mmHg, diastolic blood pressure greater than 100 mmHg, a measured glomerular filtration rate less than 70 mL/min/1.73m2, a presence or history of macroalbuminuria (>300 mg/g creatinine), or a presence or history of panel-reactive anti-HLA antibodies greater than 30% will be excluded from the study. Additional exclusion criteria relate to patient health status and treatment history.
Participants will undergo immunosuppression for a minimum of 3 weeks after Cell Pouch implantation. Immunosuppression will be optimized for another 3 weeks. Participants will then receive a transplant into the Cell Pouch of more than 3,000 islet equivalent numbers per kg of body weight of highly purified islets. The study’s primary end point is the incidence and severity of adverse events determined to be probable or highly probable to be related to the Cell Pouch. Secondary end points include the survival of endocrine tissue in the cell pouch, the proportion of participants with a reduction in severe hypoglycemic events, the proportion of participants with a reduction in HbA1c >1mg%, and insulin use. The study is taking place at the University of Chicago Medical Center. The company expects to report interim data from the second cohort in 2023.