medwireNews: Results of a phase Ib trial published in Science Translational Medicine suggest that immunotherapy with proinsulin peptide is well tolerated in patients with newly diagnosed type 1 diabetes.
“Despite over 25 years of efforts to develop immunomodulatory therapies to divert the course of type 1 diabetes, no therapeutic has yet emerged that balances robust efficacy with acceptable safety and tolerability for patients,” say study author Mark Peakman (King’s College London, UK) and colleagues.
Antigen-specific immunotherapy “has been shown in preclinical models of inflammation and autoimmunity to limit disease” and is thus being considered as an approach for type 1 diabetes, they add.
The team randomly assigned 27 adult type 1 diabetes patients with the HLA-DRB1*0401 genotype to receive injections of C19-A3, an HLA-DR4 (DRB1*0401)–restricted immunodominant proinsulin peptide, at a dose of 10 µg every 2 or 4 weeks (high and low frequency groups, respectively), or placebo injections every 2 weeks, for 6 months. All participants had received a diagnosis of type 1 diabetes less than 100 days before enrolment.
None of the participants experienced treatment-emergent serious adverse events or hypersensitivity reactions over the course of the study. Local erythematous skin reactions were experienced by 89% of the nine patients receiving high frequency C19-A3, 100% of the 10 patients in the low frequency C19-A3 group, and 50% of the eight participants receiving placebo.
Patients in the placebo group experienced a significant decline in average C-peptide levels between baseline and months 3, 6, 9, and 12, indicating a decrease in insulin reserves, and increased their daily insulin use by more than 50% from baseline to the 12-month follow-up.
However, patients receiving C19-A3 did not significantly increase their insulin use over the course of the study, and mean changes in C-peptide levels were “more modest” in these patients. Among patients receiving immunotherapy, the decline in C-peptide was only significant when comparing mean levels at baseline versus 12 months in the high frequency group.
Although these findings suggest there is “no evidence for accelerated loss of C-peptide secretion as an indicator of augmented β cell damage” with proinsulin peptide treatment, Peakman and colleagues note that the results “should be viewed with caution because C-peptide measurements can be variable, there were small numbers of subjects in each group with some imbalance between groups in baseline metabolic data, and the study was not powered to examine efficacy.”
They also caution that the small sample size, combined with disease heterogeneity, “limits opportunities to better understand dosing and identify robust immunological effects and biomarkers.”
And the team concludes: “Future studies will need to be powered for these and for efficacy, should examine whether children are similarly responsive, and begin to explore opportunities for prevention.”
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