Clinical Trials

Date: 2017-03-31

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in Diabetologia

Company: Diamyd Medical (Sweden)

Product: Diamyd®

Action mechanism:

• protein. This antigen-based diabetes therapy under development aims 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. This reduces the risk for both acute and long term diabetes complications significantly. Its active substance is the human protein GAD65 (Glutamic acid decarboxylase isoform 65 kDa).

Disease: type 1 diabetes

Therapeutic area: Autoimmune diseases - Metabolic diseases

Country: Finland, France, Germany, Italy, the Netherlands, Slovenia, Spain, Sweden and the UK

Trial details:

• The EU Phase III study is a multinational, multicenter, double-blind, randomized, placebo-controlled trial enrolling approximately 320 patients between 10 and 20 years of age who have been diagnosed with type 1 diabetes within three months. The study is being conducted at more than 60 clinics in nine European countries, i.e. Finland, France, Germany, Holland, Italy, Slovenia, Spain, Sweden and UK. One third of the patients received four injections with Diamyd®, one third received two injections with Diamyd® followed by two injections with placebo, and one third has received four injections with placebo. The injections were given on Day one, and then after one month, three months and nine months. (NCT00723411)

Latest news:

• • On March 31, 2017,  Diamyd Medical announced that a scientific article published in Diabetologia supports the notion that vaccination against influenza A (H1N1) 2009, commonly known as the Swine flu, might have had a negative impact on the outcome of the treatment with the diabetes vaccine Diamyd® in the European Phase III clinical trial conducted in 2008-2011. In the patient group receiving two doses of Diamyd®, there was greater preservation of residual insulin production when there was at least 150 days between the Swine flu vaccination and the first injection of Diamyd®. In the article published in Diabetologia, the authors show an association between vaccination against the influenza A (H1N1) 2009 (Swine flu) and the effect of the Diamyd®-vaccination in patients participating in the placebo controlled Diamyd® European Phase III trial. The study that was conducted in 2008-2011 did not reach the primary endpoint, although a clinical effect was observed in several subgroups.
• Antibodies to GAD65 were higher in all patients given the diabetes vaccine Diamyd®, and for which the time between receiving the vaccination against the Swine flu and the Diamyd®-vaccine was longer than 210 days. In the patient group receiving two doses of Diamyd® there was greater preservation of residual insulin production and a more pronounced Th2 character of the immune response when there was at least 150 days between the Swine flu vaccination and the first injection of Diamyd®. “One known element of uncertainty that has been discussed, is the possible impact another vaccination may have when given during the treament with the diabetes vaccine Diamyd® ,” says Ulf Hannelius, CEO of Diamyd Medical. “These results provide valuable new facts that will be considered in ongoing and future planning of clinical trials.”
• • On October 29, 2012, Diamyd Medical has announced that it will limit further investment in the diabetes vaccine. The company has decided to allocate a maximum of SEK 30 million (€3.5 million) over three years for the development of the diabetes vaccine Diamyd®. The ambition is to have new scientific results within three years providing opportunities for partnering with major pharmaceutical companies or other funding. Diamyd Medical’s liquid assets and short term investments amounted to SEK 380 million (€44 million) as of August 31, 2012.• On February 2, 2012, Diamyd Medical has announced that an article with the results of European Phase III study of the antigen-based diabetes therapy Diamyd® has been published in the New England Journal of Medicine ("GAD65 Antigen Therapy in Recently Diagnosed Type 1 Diabetes Mellitus".  J. Ludvigsson, D. Krisky, R. Casas, T. Battelino, L. Castaño, J. Greening, O. Kordonouri, T. Otonkoski, P. Pozzilli, J-J. Robert, H.J. Veeze and J. Palmer). The now published results were previously presented at the American Diabetes Association's 71st Scientific Sessions in San Diego, California, USA, on June 28, 2011. • On June 28, 2011, Diamyd Medical AB has reported detailed results from the European Phase III study of the antigen-based diabetes therapy Diamyd®, which, as previously announced, did not meet the primary efficacy endpoint. The study enrolled 334 patients, 10 to 20 years old, who were diagnosed with type 1 diabetes within three months of entering the study. All of the patients had some endogenous insulin production left and were GAD antibody positive at study entry. The study included three treatment arms in which a third of the patients received four subcutaneous injections of Diamyd® (day 1, 30, 90 and 270), one third received two injections of Diamyd®, and one third received placebo (non-active substance). Patients were followed for 15 months. Diamyd® was well tolerated, as demonstrated by a similar number of adverse events reported in the groups treated with Diamyd® and the placebo group. The levels of GAD antibodies increased significantly in the groups receiving Diamyd®, but not in the placebo group. The primary efficacy endpoint was change in C-peptide, a measure of endogenous insulin production, between the first study visit and the visit 15 months later. In the study, the levels of C-peptide decreased similarly in all treatment groups and, as previously reported, the primary efficacy endpoint was not met, although a small positive effect was seen. Patients treated with Diamyd® had on average 16.4 percent more remaining C-peptide at 15 months compared to those who received placebo. The p-value of the primary endpoint was 0.10. The secondary efficacy endpoints included mean daily dose of insulin, hemoglobin A1c (HbA1c) and frequency of hypoglycemia. Treatment with Diamyd® did not achieve a statistically significant effect for any secondary endpoint. Pre-specified subgroup analyses suggest that Diamyd® had an effect in several subgroups. These analyses included divisions based on gender, age, country, number of days since diagnosis at baseline and other characteristics. In the subgroup of male study participants the patients treated with Diamyd® kept 41 percent more of their C-peptide than those who received placebo (p <0.01). Another interesting observation was that among the patients who received their first injection of Diamyd® during the period March-April, the patients treated with Diamyd® kept significantly more of their C-peptide than the corresponding placebo-treated patients (p = 0.02). In the previous Phase II study with Diamyd®, all study participants received their first injection of study drug during these months and since there are seasonal variations in the immune system this may play a role for the treatment's effect on the immune system. Another factor that could contribute to the difference in outcomes between Phase II and Phase III is the use of influenza vaccine during the study periods. During the Phase III study, there was a pandemic influenza outbreak that led to many vaccinations in the study even though, originally, it was not planned to allow for influenza vaccination in conjunction with injections of study drug. Among the patients who were not vaccinated against influenza within 150 days after the first injection of Diamyd® or placebo, the p-value was 0.07. Given that the European Phase III study did not meet the primary efficacy endpoint, Diamyd Medical decided not to complete the follow-up period of the study, which therefore was closed on June 1 this year. On June 23 the Company announced the decision to suspend dosing in a parallel US Phase III study and to also initiate closure of that study. Results from Diamyd Medical's European Phase III study with Diamyd® were first reported in May 2011 (See below). The study did not meet the primary efficacy endpoint of preserving beta cell function, as measured by meal-stimulated C-peptide, although a small positive effect was seen. Safety data from the study showed that Diamyd® was well tolerated, as demonstrated by a similar number of adverse events reported in the groups treated with Diamyd® and in the placebo group. • On June 1, 2011, Diamyd Medical reports that it has decided not to complete the follow-up period of a European Phase III study with the antigen-based therapy Diamyd®. The swedish company also announced that it has regained control of the diabetes therapy Diamyd® and the active substance GAD65 following Ortho-McNeil-Janssen Pharmaceuticals election to terminate the agreement the two companies signed in June 2010 to develop and commercialize Diamyd®. The termination of the agreement follows the evaluation of the results of a European Phase III study with Diamyd® reported on May 9. The study did not meet the primary efficacy endpoint of preserving beta cell function at 15 months in patients newly diagnosed with type 1 diabetes, although a small positive effect was seen. An ongoing parallel US Phase III study, DiaPrevent, was fully enrolled in December 2010, and results are expected in the summer of 2012. In addition, the research consortium Type 1 diabetes TrialNet is conducting a Phase II trial with Diamyd® in the US and Canada with similar design. Another externally funded and researcher-initiated Phase II study with Diamyd® in progress is aiming to prevent type 1 diabetes from developing in high risk subjects. • On May 9, 2011,Diamyd Medical's European Phase III study in recently diagnosed type 1 diabetes patients, 10 to 20 years old, the antigen-based therapy, Diamyd®, did not show a statistically significant preservation of beta cell function after 15 months of follow-up compared to placebo, although a small positive effect was seen. Furthermore, Diamyd® was well tolerated as demonstrated by a similar number of adverse events across treatment groups. Detailed results will be presented at the American Diabetes Association's 71st Scientific Sessions in San Diego, CA, USA, June 24-28, 2011. As part of a planned, longer-term follow-up, the patients in the European study are currently being followed for an additional 15 months to further evaluate the safety and efficacy of Diamyd®. An ongoing parallel U.S. Phase III study, DiaPrevent, was fully enrolled in December 2010, and results are expected in the summer of 2012. • On Februray 14, 2011, Diamyd has announced that all patients have completed the main 15 month study period in this phase 3 trial. The first patient in the Diamyd EU Phase III study was enrolled in the autumn of 2008, and the trial was fully recruited in November 2009. All patients have now been followed for 15 months, which is the main study period for this trial. As part of a planned, longer term follow on study, the patients will be followed for an additional 15 months, to further evaluate the safety and efficacy of the antigen based therapy Diamyd®. In its global Phase III program, Diamyd is also conducting a similar study in the U.S., DiaPrevent, which was fully enrolled in December 2010. Diamyd expects to complete the main study period of this study during the spring of 2012. The global Phase III program aims to investigate whether Diamyd® can halt or slow the destruction of beta cells in the pancreas in type 1 diabetes, preserving the beta cell function and the body\'s own ability to control the blood sugar level. This in turn reduces the risk of both short and long term diabetes complications. In Phase II studies, the Diamyd® therapy has been shown to slow the loss of beta cell function compared to placebo. The two studies have now enrolled more than 640 recently diagnosed type 1 diabetes patients between 10 and 20 years of age in Europe and USA.

Is general: Yes