Heat‐shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double‐blind phase II study

Lazar, Liora; Ofan, R; Weintrob, Naomi; Avron, Ann; Tamir, Merana; Elias, Dana; Phillip, Moshe; Josefsberg, Z

doi:10.1002/dmrr.711

Cited by 102 publications

(68 citation statements)

References 20 publications

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“…Residual insulin secretion facilitates metabolic control and decreases the risk of keto-acidosis [3], and even modest beta cell function, with stimulated C-peptide above 0.2 nmol/l, may reduce long-term complications [4]. Type 1 diabetes is an autoimmune disease [5]; however, most attempts to use immune intervention to preserve residual beta cell function have achieved limited benefits or have been associated with adverse effects [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Treatment with anti-CD3 monoclonal antibodies appears to be the most promising treatment to date, but several patients treated in this way, as well as with anti-CD20 monoclonal antibodies, have experienced treatment-related adverse events [20,21].…”

Section: Introductionmentioning

confidence: 99%

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

et al. 2010

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Aims/hypothesis The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD 65 (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Methods Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 μg of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with <6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. Results One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GADalum group fasting C-peptide was 0.332±0.032 nmol/l at day 1 and 0.215 ± 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354± 0.039 and 0.184±0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GADalum group than in the placebo-treated group after 4 years.

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Section: Introductionmentioning

confidence: 99%

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

et al. 2010

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“…Thus, even if the tolerizing approach in mice may form the basis for the subsequent development of such a vaccine in humans, it is rather improbable that the same HSP60 peptide candidate will emerge as atherogenic in both species. However, promising results from clinical trials for treating rheumatoid arthritis and type I diabetes are currently ongoing (Prakken et al 2004;Raz et al 2001Raz et al , 2007Huurman et al 2007Huurman et al , 2008Lazar et al 2007;Koffeman et al 2009). A better understanding of these networks is highly warranted.…”

Section: Discussionmentioning

confidence: 99%

Tolerization against atherosclerosis using heat shock protein 60

Wick

2016

Cell Stress and Chaperones

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“…Primary outcome was glucagon-stimulated C-peptide at 10 months, which was higher in the DiaPep277 group than in the placebo group, an effect that was sustained with followup to 18 months (27). Four additional phase 2 studies showed results that were ambiguous at best, with no clear benefit (28)(29)(30). Nonetheless, the sponsor mounted two full-scale phase 3 trials.…”

Section: Misleading Pilot Studiesmentioning

confidence: 99%

Prevention and Reversal of Type 1 Diabetes—Past Challenges and Future Opportunities

Skyler

2015

Diabetes Care

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Over the past three decades there have been a number of clinical trials directed at interdicting the type 1 diabetes (T1D) disease process in an attempt to prevent the development of the disease in those at increased risk or to stabilize—potentially even reverse—the disease in people with T1D, usually of recent onset. Unfortunately, to date there has been no prevention trial that has resulted in delay or prevention of T1D. And, trials in people with T1D have had mixed results with some showing promise with at least transient improvement in β-cell function compared with randomized control groups, while others have failed to slow the decline in β-cell function when compared with placebo. This Perspective will assess the past and present challenges in this effort and provide an outline for potential future opportunities.

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Heat‐shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double‐blind phase II study

Abstract: One-year treatment with DiaPep277 at a dosage of 1 mg is safe for use and well tolerated in children with recent-onset T1DM. However, it appears to have no beneficial effect in preserving beta-cell function or improving metabolic control.

Cited by 102 publications

References 20 publications

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial

Tolerization against atherosclerosis using heat shock protein 60

Prevention and Reversal of Type 1 Diabetes—Past Challenges and Future Opportunities

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