Clinical Trials

Date: 2017-06-22

Type of information: Results

phase: 2a

Announcement: results

Company: Zealand Pharma (Denmark) Beta Bionics (USA - MA)

Product: dasiglucagon (ZP4207) and bionic pancreas

Action mechanism:

• glucagon analogue/artificial pancreas/medical device. Dasiglucagon (ZP4207) is an analogue of human glucagon, invented by Zealand. Glucagon is a peptide hormone, produced by alpha cells of the pancreas and secreted to prevent blood glucose levels dropping too low, thus playing an essential role for a well-functioning metabolic system. Dasiglucagon has been shown to have a high solubility and a strong physical and chemical stability profile in liquid solution, while data from preclinical studies suggest that it is comparable to native glucagon in releasing glucose stores into the blood stream.
• Zealand Pharma entered into a collaboration with Beta Bionics, a Boston-based company, earlier this year. Beta Bionics is developing a dual-hormone artificial pancreas system based on advanced technology that was conceived and refined at Boston University and has been undergoing clinical trials for nearly 10 years at the Massachusetts General Hospital and, more recently, Stanford University, the University of North Carolina and the University of Massachusetts. The technology is being integrated at Beta Bionics into a pocket-sized wearable medical device called the iLet™.

Disease: type 1 diabetes

Therapeutic area: Metabolic diseases

Country: Germany, USA

Trial details:

• The purpose of the first study is to determine whether the Bionic Pancreas with ZP4207 (dasiglucagon) is feasible to improve glycemic control in adults with type 1 diabetes mellitus. Steven J. Russell, MD, Massachusetts General Hospital Diabetes Research Center in Boston, is the principal investigator of the trial.(NCT02971228)
• The other trial was a double-blind, randomized, four-period, sequential complete crossover trial in patients with type 1 diabetes. Four different doses of dasiglucagon were tested under normal blood glucose level (euglycemia) and low blood glucose level (hypoglycemia) conditions and with reference to responses observed with freshly reconstituted glucagon (NCT02916251).

Latest news:

• • On June 22, 2017, Zealand Pharma and Beta Bionics announced a positive outcome from the Phase 2a clinical safety trial using dasiglucagon in the dual-hormone artificial pancreas system, developed at Boston University and licensed to Beta Bionics. The study was conducted at the Massachusetts General Hospital Diabetes Research Center in Boston, MA, USA, with Steven J. Russell, MD, as Principal Investigator.
• The aim of the Phase 2a clinical trial was to assess the safety, efficacy and tolerability of dasiglucagon when administred automatically using the iLet™ algorithms. The trial included 10 adult patients with type 1 diabetes, and a marketed recombinant glucagon was used as comparator. The test conditions were chosen to optimize the opportunity to evaluate the ability of dasiglucagon (and comparator) to maintain blood glucose in the desired target glycemic range: subjects arrived fasting at the clinic for the 8 hour testing period, they had their first meal at lunch-time at which time they injected a standard insulin bolus. Their basal rate of insulin was up to twice their normal rate, and following the meal, they were asked to perform 30 minutes of exercise to stimulate the administration of glucagon by the system.
• The automated dosing algorithms were observed to deliver both dasiglucagon and recombinant glucagon in response to falling blood glucose. During treatment, even with subjects placed under the challenging conditions of the trial, glucose levels were in the range of 70-180 mg/dl approximately 70% and 65% of the time respectively for dasiglucagon and recombinant glucagon.
• Dasiglucagon infusion was observed to be safe and well tolerated in the trial, with no injection site reactions noted. No severe hypoglycemic episodes were observed and time below 60 mg/dl glucose was approximately 13% and 18% for dasiglucagon and recombinant glucagon, respectively. A few subjects experienced mild nausea with both dasiglucagon and the recombinant glucagon.This trial, along with the pharmacodynamic data from the recently completed dasiglucagon mircrodose trial, provides the foundation for further clinical development of dasiglucagon in the iLet™ pump system in out-patient trials. Zealand Pharma is now looking forward to initiating the Phase 2b trial with dasiglucagon in the iLet™ pump system.
• • On May 23, 2017, Zealand Pharma  announced results from a Phase 2a trial following administration of the multiple-dose version of dasiglucagon in adult patients with type 1 diabetes. The trial was initiated in December 2016 to assess the efficacy, safety and tolerability of different doses of the concentrated formulation of dasiglucagon for pump use. The primary objective was to characterize the pharmacokinetic and pharmacodynamic properties of dasiglucagon 4 mg/ml formulated with preservatives.
• A clear dose-response with increases in blood glucose levels was observed across the broad dose range tested, allowing for titration of dasiglucagon to counteract present or incumbent hypoglycemia. All dasiglucagon doses provided clinically relevant mean increases in blood glucose (mean plasma glucose increases of 20 mg/dl or more) under both euglycemic and hypoglycemic conditions.
• Dasiglucagon and glucagon were observed to be safe and well-tolerated in the trial, with no injection site reactions observed with dasiglucagon. Nausea and vomiting were the most frequent side effects observed, predominantly at the higher dose-levels, with both dasiglucagon and Glucagon.
• Zealand expects to report top-line results from a second Phase 2a trial, which is conducted under this partnership, by the end of June 2017, after which the company will decide on the next clinical development steps.• On December 13, 2016, Zealand Pharma announced that it has dosed the first patients in its Phase IIa clinical trial with dasiglucagon in a dual-hormone artificial (or bionic) pancreas system from Beta Bionics. The multiple-dose version of dasiglucagon is intended for use in a dual-hormone artificial pancreas system to better control hypoglycaemia and, potentially, hereby provide insulin treated diabetes patients with options for easier and more effective management of their disease. The study will test the effectiveness of the stable glucagon analogue dasiglucagon in the dual-hormone bionic pancreas, comparing it with the unstable glucagon formulation that the company has used in all of its previous studies.
• The aim of the Phase IIa clinical trial with Beta Bionics is to assess, for the first time, the safety, efficacy and tolerability of dasiglucagon as part of the Beta Bionics dual-hormone artificial (bionic) pancreas system in adult patients with type 1 diabetes, compared to a recombinant market glucagon. In collaboration with Beta Bionics and Boston University, the trial is conducted at the Massachusetts General Hospital Diabetes Research Center in Boston, MA, USA, with MD Steven J. Russell as Principal Investigator.
• Results from the trial are expected in H1 2017.

Is general: Yes