Clinical Trials

Date: 2017-07-27

Type of information: Publication of results in a medical journal

phase: 1

Announcement: publication of results in The New English Journal of Medicine

Company: Diamyd Medical (Sweden)

Product: Diamyd® and vitamin D

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.

Disease:

type 1 diabetes

Therapeutic area: Autoimmune diseases - Metabolic diseases

Country: Sweden

Trial details:

• DIAGNODE is an open label pilot study with five patients between 18 and 30 years of age who have been diagnosed with type 1 diabetes within 6 months. An initial evaluation will be made after 6 months, with a focus on safety and immunological markers, and the patients will thereafter be followed for another 24 months. All five participants will receive a low dose (4?g) of Diamyd® in the lymph node on three occasions. Diamyd® is in this study combined with a high dose of vitamin D. The vitamin D is provided in order to down regulate the immune system’s inflammatory components to thereby increase the diabetes vaccine’s tolerance inducing effect in regard of preserving the patient's insulin producing capacity. (NCT02352974)

Latest news:

• • On July 27, 2017, Diamyd Medical announced that  additional preliminary interim results from intralymphatic study with Diamyd® published as part of scientific correspondence in The New English Journal of Medicine. New immunological data from the DIAGNODE-1 trial, published as part of a correspondence in the medical periodical show a predominant Th2 response when Diamyd® is administered directly into the lymph node being stronger than observed when injecting it under the skin. The correspondence and data are based on the original article published in NEJM on February 16, 2017, by Professor Johnny Ludvigsson, Principal Investigator and sponsor of the open label pilot trial DIAGNODE-1 (See below). In addition to these new immunological data from the researcher-initiated trial DIAGNODE-1 published in NEJM, data from six of a total of twelve patients that have been followed for 15 months that support previously reported interim results were recently press released by Diamyd Medical in a fourth interim report on July 6, 2017.
• • On July 6, 2017, Diamyd Medical  announced that a fourth interim report from DIAGNODE-1 shows a positive clinical progression in terms of the body’s own capacity to produce insulin, as well as long-term blood sugar and insulin dose when half of the patients have been followed for 15 months.In this report, results are presented for six out of a total of twelve patients that have been followed for 15 months. Safety continues to look good and no serious side effects have been reported. On average, the group’s own ability to produce insulin (measured by C-peptide, AUC) decreased by 10.8 % while fasting C-peptide increased by 23%. Meanwhile, HbA1c and insulin dose were reduced by 31 and 39 %, respectively. In summary, these data indicate that the disease progression continues to be positive at 15 months for these six patients and is in line with previously reported results from the trial. • On June 7, 2017,  Diamyd Medical, together with Professor Johnny Ludvigsson at Linköping University, Principal investigator and Sponsor, has decided to close the recruitment of patients in the DIAGNODE-1 trial to begin the follow-up of patients already now and focus on the larger follow-up trial DIAGNODE-2. According to the protocol, the trial may include about 15 patients and a decision has been taken to close the recruitment at these 12 patients to initiate follow-up of the patients and to prepare for the larger phase II trial DIAGNODE-2. 6-month results from all 12 patients will be presented in the fourth quarter of 2017, when all patients have completed their 6-month visit, data have been monitored, collected and analyzed. 6- and 15-month results on a limited number of patients may also be expected to be presented at some prior occasions preceding discussions with potential partners, presentations at scientific meetings or for other purposes where results have an important strategic or operational purpose.
• • On February 16, 2017, Diamyd Medical announced that an article by Professor Johnny Ludvigsson, Principal Investigator and sponsor of DIAGNODE-1, was published in the New England Journal of Medicine. The article summarizes the preliminary interim results based on study data from six patients who have been followed for at least six months, of which four have been followed for at least 15 months.• On October 24, 2016, Diamyd Medical announced that the second interim report from DIAGNODE-1, preliminary shows that the treatment after 15 months appears to be safe and tolerable and that the clinical progression in patients is positive in terms of the body’s own capacity to produce insulin, as well as long-term blood sugar and insulin dose.  “The results, which admittedly are based on few patients, look very promising,” says Professor Johnny Ludvigsson at Linköping University, principal investigator and the sponsor of the study, “It is particularly interesting that the beta cell function rather looks to have improved from 6 to 15 months of follow up. My conclusion, which I will present at ISPAD, is that a low dose of the diabetes vaccine Diamyd® given directly into the lymph node, in combination with oral treatment with vitamin D, appears to be tolerable and safe, and provides a strong immune response that could preserve the own ability to produce insulin.” Professor Johnny Ludvigsson reports that preliminary 15-month data for the first four patients, followed for 15 months, indicates that the safety is good and no serious side effects have been reported. On average, the group decreased its ability to produce insulin (measured by C-peptide AUC) by 6% while fasting C-peptide increased by 34%. Meanwhile, HbA1c (a way to measure long-term blood sugar) and insulin decreased by 22 and 24% respectively. Earlier this year, Professor Johnny Ludvigsson reported preliminary 6-month data for four patients and now with six-month data for additional two patients, the result for the total of six patients at 6 months is available. The safety looks good and no serious side effects have been reported. On average, the group’s own ability to produce insulin (measured by C-peptide AUC) has increased by 3% while fasting C-peptide has decreased by 3%. Meanwhile, HbA1c and insulin dose were reduced by 38 and 28% respectively. This indicates that the previously reported clinical results have not changed when observing six patients compared to the previous four patients.
• Immunological markers have been evaluated preliminarily, which suggests that the diabetes vaccine Diamyd® given directly into the lymph node provides a clear and desired re-balancing of the immune system. Here has the so-called Th1 response - which is associated with autoimmunity in type 1 diabetes – been directed towards the so-called Th2 response, which is the desired immunological response with the aim of maintaining the insulin production.
• • On September 7, 2016, Diamyd Medical provided update on clinical studies with Diamyd® for the treatment and prevention of type 1 diabetes. The company announced that the open label study DIAGNODE-1 is not yet fully enrolled.
• • On April 21, 2016, Diamyd Medical announced that Professor Johnny Ludvigsson will present preliminary immunological interim results from four patients in the pilot study DIAGNODE-1 at the diabetes meeting SSSD in Reykjavik 21-22 April. The interim results indicate that administration of a low dose of the diabetes vaccine Diamyd® in lymph glands clearly re-balances the immune system towards a desired so called Th2 response. As previously reported, the treatment appears to be safe and tolerable and the clinical progression seems positive in terms of the body’s own capacity to produce insulin, as well as better long-term blood sugar and lower insulin dose, even if no conclusions can be drawn in these few patients who still may be in the so called honeymoon-phase, often characterized by some regression of the disease. Professor Ludvigsson with team have now also evaluated immunological markers, which indicate that the diabetes vaccine Diamyd®administered directly into lymph nodes generates a clear and desired immune deviation. Here, the so called Th1 response – which is associated with the autoimmunity in type 1 diabetes – is skewed towards a so called Th2 response, which is the desired immunological response when aiming to preserve endogen insulin secretion. This is shown by the relative secretion of cytokines where, upon the immune system’s contact with GAD65, a larger concentration of for example IL-13 is observed compared to IFN-gamma. A pronounced increase in GAD antibodies can also be seen in the four patients.•  On April 1, 2016, Diamyd Medical announced that DIAGNODE-1 has been approved by the Swedish Medical Products Agency and the Ethics Review Board to be expanded from five to nine patients and to include children from 12 years of age. Professor Johnny Ludvigsson, principal investigator and sponsor of DIAGNODE-1, has submitted a first preliminary evaluation of data from the first four patients that have been monitored for six months in the study, as an abstract for the diabetes meeting “51st Annual Meeting of the Scandinavian Society for the Study of Diabetes (SSSD)” to be held in Reykjavik, Iceland, on April 21-22, 2016. This evaluation preliminarily shows that the treatment appears to be safe and tolerable. Even if the clinical progression in patients shows certain positive data in terms of the body’s own capacity to produce insulin, as well as better long-term blood sugar and lower insulin dose , no conclusions are drawn regarding metabolic parameters in these few patients who still may be in the so called honeymoon-phase, often characterized by some regression of the disease. This data has served as the basis for an application to expand the study from five to nine participants and also to include children and adolescents from 12 years of age. This application has now been approved by the Swedish Medical Products Agency and the Ethics Review Board.
• •  On February 11, 2016, Diamyd Medical announced that the first six-month interim report from DIAGNODE-1, a clinical pilot study in which the diabetes vaccine Diamyd® is administered directly into lymph nodes, preliminarily shows that the treatment appears to be safe and tolerable and that the clinical progression in patients is positive in terms of the body’s own capacity to produce insulin, as well as long-term blood sugar and insulin dose. Professor Johnny Ludvigsson reports that the preliminary data for the four patients, with an average age of 21.8, who have been monitored for six months indicates good safety and no serious side effects have been reported. HbA1c (a way of measuring long-term blood sugar) decreased in all four patients. The insulin dose was reduced in three of the four patients. Over the six-month period the body’s own ability to produce insulin (measured as C-peptide, AUC) increased in two of the patients by 32 and 6 percent respectively, and decreased in two of the patients by 29 and 2 percent, respectively. On average, the group increased its ability to produce insulin by 2 percent, while HbA1c and insulin dose decreased by 32 and 25 percent, respectively. Immunological parameters were also preliminarily evaluated, which showed a clear effect on the immune response compared with other studies in which the diabetes vaccine Diamyd® was injected subcutaneously with a higher dose, instead of a low dose injected directly into the lymph nodes, as in this study. Professor Johnny Ludvigsson submitted an abstract with these interim results to the “51st Annual Meeting of the Scandinavian Society for the Study of Diabetes (SSSD)”, in Reykjavik, Iceland, which will be held on April 21-22, 2016.
• •  On January 20, 2016, Diamyd Medical announced  that a first six month interim report for DIAGNODE-1 is intended to be presented during the first quarter of 2016. The study is open labeled, meaning not placebo-controlled. Professor Johnny Ludvigsson, Linköping University, is principal investigator and sponsor of the study. The report also announced that pre-clinical testing is ongoing to produce antigen presenting cells with the aim to be used in cell therapy treatment.
• • On February 3, 2015, Diamyd Medical informed that the first patient has been enrolled in the DIAGNODE study. In the study a new way to administer the Diamyd® diabetes vaccine is tested, directly into inguinal lymph nodes. DIAGNODE is the first study of its kind, where a low dose of Diamyd® is administered directly into lymph nodes in combination with treatment with vitamin D. The concept, for which Diamyd Medical has submitted a patent application, can be compared to the development in allergy therapy, where the administration of allergen into lymph nodes has significantly improved efficacy. 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  at Linköping University.

   

Is general: Yes