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Diabetes Clinical Trials

DIAMYD® FOR PREVENTION OF TYPE 1 DIABETES PHASE II STUDY – DIAPREV-IT
Diamyd® is since 2009 being evaluated in a Swedish researcher initiated Phase II study, DiAPREV-IT. The study is double-blind and placebo-controlled and includes a total of 50 children aged four and older who through analysis of diabetes markers, so-called auto-antibodies, in the blood are demonstrated to be at high risk of developing type 1 diabetes. Half of the children receive two injections of Diamyd®, and the remaining half receive placebo (inactive substance). The children will be monitored for a total of five years by means of sampling and glucose tolerance tests to evaluate the beta cell function, a measure of the body's own ability to regulate blood sugar levels. The last participant was enrolled in the study in January 2012. The first results are expected to be compiled in 2015, three years after the last participant was enrolled. The study is being conducted by a research group at Lund University and is led by Dr. Helena Elding Larsson, a pediatrician in Malmö and researcher at Lund University. The study is funded by research grants. Diamyd Medical has participated in the design of the study, is responsible for providing study drug, and can utilize the study results.

Preventive treatment with the diabetes vaccine Diamyd® is intended to intervene in the autoimmune process at an early stage, and thus prevent the disease from developing. Today there is no treatment that can halt the progress of disease in type 1 diabetes.

DIAMYD® IN COMBINATION STUDIES – DIABGAD-1
Diamyd® is since 2013 being evaluated in a Swedish researcher initiated Phase II combination study, DIABGAD-1. The study is a double-blind, randomized and placebo-controlled Phase II study including a total of 60 participants between 10 and 18 years old, newly diagnosed with type 1 diabetes. The study will comprise a total of 30 months, with a first analysis focusing on immunological markers already after 6 months.

The study, which is the first study of its kind, combines the diabetes vaccine Diamyd® with relatively high doses of vitamin D and the anti-inflammatory drug ibuprofen. The purpose of the treatment is to preserve the body's own ability to control the blood sugar level in children and adolescents newly diagnosed with type 1 diabetes.

Four different treatment groups, each including 15 participants, will be evaluated: the first group will receive one prime injection of Diamyd® and a booster injection 4 weeks later, combined with ibuprofen for 90 days and vitamin D for 450 days; the second group will receive one prime injection of Diamyd® and a booster injection 4 weeks later, and vitamin D for 450 days; the third group will receive two prime injections of Diamyd® and two booster injections 4 weeks later, and vitamin D for 450 days; and the fourth group will receive placebo only.

The study will also evaluate the effect of a double dose of Diamyd® and the protein GAD.

The study is being conducted at several pediatric diabetes clinics in Sweden and is led by Professor Johnny Ludvigsson, at Linkoping University. The study is funded by research grants. Diamyd Medical has participated in the design of the study, is responsible for providing study drug and to cover certain other costs, and can utilize the study results.


PHASE III STUDY - TYPE 1 DIABETES
In May 2011 Diamyd reported results from a European Phase III study with Diamyd®. Unfortunately the study 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. In June 2011, the Company decided not to complete the follow-up period of the European Phase III study of Diamyd® and to also initiate the closure of a parallel US Phase III study.

The European Phase III 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 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.

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 was 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.

The European Phase III study was published in February 2012 in the prestigious journal The New England Journal Medicine.


TRIALNET STUDY - TYPE 1 DIABETES
The Phase II study conducted by the American research consortium Type 1 Diabetes TrialNet was a multicenter, randomized, double-blind study that recruited 145 patients, 3 to 45 years old, in the United States and Canada. The patients, diagnosed with type 1 diabetes within three months of entering the study, were divided into three equal groups of which one group received three injections of Diamyd® (day 1, 30 and 90), one group received two injections of Diamyd® and one injection of placebo, and one group received three injections of placebo. All of the patients had some endogenous insulin production left and were GAD-antibody positive at entering the study. The patients have been followed for 24 months.

After the first 12 months of the study, it did not reach the primary efficacy endpoint of preserving endogenous insulin production, as measured by meal-stimulated C-peptide, in patients treated with Diamyd® compared to placebo. 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.

The 12 month study results were published in July 2011 in the medical journal The Lancet. .


PHASE II STUDY - TYPE 1 DIABETES
During 2005 to 2007 a 30-month randomized, double-blind, placebo-controlled Phase II study of Diamyd® was carried out, encompassing 70 children and adolescents between 10 and 18 years old with type 1 diabetes. Significant long-term efficacy was demonstrated in preserving beta cell function, i.e. endogenous insulin producing capacity. The treatment was well received by patients, their doctors and family members. No serious side effects related to the treatment were reported in the study. The results were published in The New England Journal of Medicine in the fall of 2008.


PHASE II STUDY - LADA

Diamyd Medical has completed a randomized, double-blind, placebo-controlled Phase II study encompassing 47 LADA patients, where various doses of Diamyd® were tested. Depending on their study arm, the patients received 2 injections of either 4, 20, 100 or 500 µg Diamyd® or placebo at a four-week interval. The study was unblinded after six months and the patients were followed for another four and a half years. The study results demonstrate that the best dose of Diamyd® was 20 µg. A five year follow-up of the participants showed that the risk that a LADA patient will need to begin insulin treatment is significantly reduced after treatment with the antigen-based therapy. Only 14 percent of the patients in the group that received 20 µg of Diamyd® needed insulin after five years following the initial injection, versus 64 percent in the placebo group. No serious side effects from Diamyd® were reported during the five-year period.

The results were presented at the European Association for the Study of Diabetes (EASD) meeting in September 2008, and were published in the European scientific diabetes journal Diabetologia in April 2009.