Clinical Trials

Date: 2016-09-07

Type of information: Completion of patient enrollment

phase: 2

Announcement: completion of patient enrollment

Company: Diamyd Medical (Sweden)

Product: combination of Diamyd®, vitamin D and etanercept

Action mechanism:

• protein. Diamyd® is an antigen-based diabetes therapy under development to prevent, delay, or stop the autoimmune attack on beta cells in type 1 diabetes and other forms of autoimmune diabetes, thereby preserving the body's capacity to regulate blood sugar. The active substance in the Diamyd® diabetes vaccine is glutamic acid decarboxylase isoform 65kDa (GAD). GAD is one of the most important targets when the immune system attacks the beta cells in autoimmune diabetes. Accordingly, GAD is an autoantigen. Treatment using Diamyd® is intended to stop the autoimmune attack against the beta cells by inducing tolerance to GAD.
• fusion protein/TNF inhibitor. Etanercept is a TNF-alpha inhibitor used in rheumatic diseases and is approved in Sweden, for example, for treating children with juvenile idiopathic arthritis (JIA).
• Diamyd® has shown an overall 16% efficacy (p=0.10) in a European Phase III trial and a good safety profile. Data from clinical trials shows that Diamyd® activates components that down-regulate the immune system as well as components that increase inflammation in type 1 diabetes. By combining the diabetes vaccine with etanercept, the inflammatory response is reduced and the diabetes vaccine’s down-regulating, tolerance-inducing effect can have a greater impact. In turn, Vitamin D further down-regulates the immune system’s inflammatory components in order to strengthen the efficacy of the diabetes vaccine. Both vitamin D and etanercept are also considered to have a direct positive effect on the beta cells.

Disease: type 1 diabetes

Therapeutic area: Metabolic diseases

Country: Sweden

Trial details:

• The new trial will be conducted at several pediatric diabetes clinics throughout Sweden. The participants will first receive treatment with vitamin D and etanercept for the duration of one month. Two injections with Diamyd® will then be administered one month apart. Treatment with etanercept will continue for a total period of 90 days, and the vitamin D therapy for 15 months. An initial evaluation will take place six months after all patients have been included. The participants will subsequently be monitored for another 24 months.
• Ongoing development work is aimed at enhancing the efficacy of the treatment and providing the right conditions for the diabetes vaccine to exert an effect by combining Diamyd® with other agents and to treat earlier in the disease process. New approaches are being evaluated in several clinical studies together with different teams of researchers. Today, two researcher-initiated clinical studies with Diamyd® are in progress and an additional four have recently received regulatory approval and are being launched. These studies are being financed through research grants, while Diamyd Medical is providing the study drugs and covers certain other costs, and has participated in the design of the studies and is also able to utilize the findings of the studies.
• DIABGAD-1 is a blind, placebo-controlled study, where Diamyd® is being tested in combination with ibuprofen and vitamin D. All of the participants have been enrolled in the study and the initial six-month results, focusing on immunological markers, are expected to be presented in the beginning of 2015. The study is taking place in Sweden led by Professor Johnny Ludvigsson at Linköping University.
• DIAPREV-IT is a blind, placebo-controlled study, where Diamyd® is being tested in children with early stages of type 1 diabetes, meaning that they have been found to have an ongoing autoimmune process but do not yet have any clinical symptoms of diabetes. A total of 50 participants from the age of four have been enrolled in the study, which will last for five years. The aim of the study is to evaluate whether Diamyd® can delay or prevent the participants from presenting with type 1 diabetes. The study is taking place in Sweden led by Dr. Helena Elding Larsson at Lund University. All of the participants have been enrolled in the study and results are expected at the end of 2016.
• Diamyd®/GABA is a blind, placebo-controlled study, where Diamyd® is being tested in combination with GABA. The study will comprise a total of 75 patients between the ages of 4 and 18 who have been newly diagnosed with type 1 diabetes, and will continue for a total of 12 months. The aim of the study is to test whether the combination treatment can preserve the body’s residual capacity to produce insulin. The study is taking place in the US led by Professor Kenneth McCormick at the University of Alabama at Birmingham and is in the start-up phase.
• DIAPREV-IT 2 is a blind, placebo-controlled study, where Diamyd® is being tested in combination with vitamin D in children with early stages type 1 diabetes, meaning that they have been found to have an ongoing autoimmune process but do not yet have any clinical symptoms of diabetes. A total of 80 participants between the ages of 4 and 18 will be enrolled in the study, which will last for five years. The aim of the study is to evaluate whether Diamyd® can delay or prevent the participants from presenting with type 1 diabetes. The study is taking place in Sweden led by Dr. Helena Elding Larsson and is in the start-up phase.
• DIAGNODE is an open label study, where Diamyd® is administered directly into lymph nodes in combination with treatment with vitamin D. The study will comprise a total of five patients between the ages of 18 and 30 who have been newly diagnosed with type 1 diabetes, and will continue for a total of 30 months. The aim of the study is to evaluate the safety of the combination treatment and the effect on the immune system and the patients’ insulin producing capacity. The study is taking place in Sweden led by Professor Johnny Ludvigsson and is in the start-up phase.
• EDCR IIa is an open label study, where Diamyd® is combined with etanercept and vitamin D. The study will comprise a total of 20 patients between the ages of 8 and 18 who have been newly diagnosed with type 1 diabetes, and will continue for a total of 30 months. The aim of the study is to evaluate the safety of the combination treatment and the effect on the immune system. The study is led by Professor Johnny Ludvigsson at Linköping University, principal investigator and sponsor of the study.

Latest news:

• • On September 7, 2016, Diamyd Medical provided update on clinical studies with Diamyd® for the treatment and prevention of type 1 diabetes. The phase II study EDCR IIa now is fully enrolled and that results from a first evaluation after 6 months are estimated to be presented during the second quarter of 2017.  All 20 patients are now included in the Phase II study EDCR IIa (Etanercept-Diamyd®-Combination-Regimen), which runs at eight pediatric diabetes clinics in Sweden. The study will last 30 months after all patients have been included. The purpose of the study is to evaluate the safety of the combination treatment and its effects on the immune system in children and adolescents with recent-onset type 1 diabetes. A first evaluation will be conducted after 6 months with a focus on immunological markers, the 6-month analysis will be able to start at the end of the first quarter of 2017 and the results thus be presented in the second quarter of 2017.
• • On March 23, 2016, Diamyd Medical announced that a first six-month interim report comprising five patients in EDCR IIa, a pilot researcher-initiated clinical study in which the diabetes vaccine Diamyd® is combined with two other already approved agents, the immunosuppressive drug etanercept and vitamin D, preliminary shows the treatment is safe and tolerable. No serious side effects have been reported. The study is included in a series of combination studies with the diabetes vaccine Diamyd® to enhance the effect (16%, p=0.1) previously seen in a European Phase III study including 334 newly diagnosed type 1 diabetes patients.
• A total of 13 of 20 patients are now included in the EDCR IIa study and the first preliminary safety data from the five first patients who have been followed for six months, i.e. five months after the first of two injections of the diabetes vaccine Diamyd®, are presented. Professor Johnny Ludvigsson reports that preliminary data for the five patients, with an average age of 11.6 years, who have been monitored for six months, indicates good safety and no serious side effects have been reported. As for diabetes variables, such as endogenous insulin secretion, HbA1c (a way of measuring long-term blood sugar) and insulin dose, the number of patients are too few, and the duration – 5 months after the first injection of Diamyd® – is too short to draw any conclusions. Immunological parameters have not yet been evaluated. The study will now continue to include the remainder of the participants to the study and follow them for 6, 15 and 30 months.
• • On November 25, 2014, Diamyd Medical announced that the Swedish Medical Products Agency has approved another new researcher-initiated combination study with the Diamyd® diabetes vaccine. In the study, Diamyd® will be combined with two other agents - vitamin D and the immunosuppressive drug etanercept. The newly approved study, EDCR IIa (Etanercept-Diamyd-Combination-Regimen), comprises 20 children and adolescents between 8 and 18 years who have recently been diagnosed with type 1 diabetes. It is an open-label trial, which means that all participants will receive active combination therapy. The aim of the trial is to evaluate the combined therapy of vitamin D, etanercept and the Diamyd® diabetes vaccine from a safety perspective, and how the immune system is affected.  “The idea is that etanercept will suppress those parts of the immune system that are activated during the autoimmune process in new onset type 1 diabetes,” says Professor Johnny Ludvigsson at Linköping University, principal investigator and sponsor of the study. “The aim of this and the vitamin D therapy is to improve the efficacy of the diabetes vaccine and thus maintain the body’s residual capacity to make insulin. This is not unlike the original rationale for Diamyd® as a single agent treatment, but now expanded with important modifications based on the knowledge gained from previous clinical trials of the diabetes vaccine.”

Is general: Yes