GI Dynamics has received approval of an investigational device exemption (IDE) from the US Food and Drug Administration (FDA) to start enrollment in a pivotal trial assessing the safety and efficacy of EndoBarrier in the US pending Institutional Review Board (IRB) approval.
Image: The US FDA’s Center for Devices and Radiological Health. Photo: courtesy of The U.S. Food and Drug Administration.
The primary endpoint of the pivotal trial (GID 18-1) is reduction in average blood sugar levels (HbA1c) at 1 year.
The pivotal trial will consist of randomized EndoBarrier implant and control arms; both arms will receive identical lifestyle therapy that complies with the most current American Heart Association guidelines.
The study is approved for staged enrollment, with the initial approval for treatment of up to 67 study participants including 50 EndoBarrier and approximately 17 control participants.
Following FDA review of the interim safety report, the company will apply for approval to expand enrollment to a planned total study population of approximately 240 participants. The FDA has recommended certain study modifications that will be submitted by the company in an IDE supplement.
GI Dynamics president and CEO Scott Schorer said: “This IDE approval is the result of more than two years of scientific investigation and research focused on clinical trial design in collaboration with the FDA, with the intent of designing a robust pivotal trial focused on the treatment of type 2 diabetes.
“EndoBarrier remains one of the few technologies focused on the primary target of achieving glycemic control for patients diagnosed with type 2 diabetes that is not bariatric/metabolic surgery or anti-diabetes medication.”
GI Dynamics leveraged clinical data from nearly 4,000 EndoBarrier implants since inception, the initial US clinical trial (ENDO Trial), multiple investigator-initiated clinical trials, two ongoing registries (ABCD Worldwide EndoBarrier Registry, German EndoBarrier Registry), and the comprehensive EndoBarrier meta-analysis recently published in the American Diabetes Association’s (ADA) Diabetes Care journal.
Patient safety is of paramount importance to GI Dynamics. The company and the FDA have agreed to a multiple stage pivotal trial and the implementation of safety monitoring procedures during the study.
The approved Stage I will consist of the first 50 EndoBarrier recipients and approximately 17 control arm participants.
When the first 50 EndoBarrier recipients have reached the 6-month (post implantation) follow-up, a Stage I safety report will be provided to the FDA for review. Upon completion of Stage I and with FDA approval, enrollment of the remaining participants is planned for a total of 240 participants.
In addition, GI Dynamics and the FDA have agreed on several specific safety events that, if reported, will cause enrollment to be stopped while the GID 18-1 Data Safety Monitoring Board, GI Dynamics, and the FDA conduct a review of all study safety data to determine whether the study may continue.
The specific safety events that would cause the enrollment to stop during Stage I are presented as follows:
- One (1) hepatic abscess requiring a procedure other than image-guided fine needle aspiration (FNA) and/or oral antibiotic therapy
- Three (3) hepatic abscesses requiring oral antibiotics with or without fine needle aspiration
- One (1) instance of device-related bleeding requiring transfusion or embolization or Intensive Care Unit (ICU) care
- Three (3) instances of endoscopic intervention that includes cauterization or endoscopic clipping of a bleeding lesion
GI Dynamics, in conjunction with its scientific and medical advisors and leveraging significant investigative work and analysis, has implemented multiple clinical risk management steps to mitigate the risk of occurrence of all known safety events.
This includes the elimination of proton pump inhibitors (which are thought to increase liver abscess risk), refinement of inclusion criteria, addition of multiple exclusion criteria, the implementation of a higher threshold of failed medical therapy prior to EndoBarrier treatment, and increased patient monitoring with the intent of reducing patient risk and addressing clinical issues identified in the past, such as liver abscess.
“The GID 18-1 trial design is intended to address the patient population that has failed lifestyle and medical therapy prior to insulin use,” said Schorer. “This study will gather data on insulin sensitivity, the avoidance of insulin use, cardiovascular risk factor reduction (as measured by blood pressure, cholesterol, and triglycerides), and the reduction of severity of specific types of liver disease: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). This pivotal trial is a substantial undertaking that is intended to create significant clinical value. The team of employees, clinicians, and directors of the company are committed to investigating the safety and efficacy of EndoBarrier to treat type 2 diabetes and associated comorbidities.”
Subject to securing additional financing in 2018, GI Dynamics expects to complete enrollment of Stage I of the study during the first half of 2019.
Source: Company Press Release