• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

Administration of DiaPep277® is safe and represents a promising therapeutic strategy in patients with recent-onset type 1 diabetes (T1DM). Results of two large Phase 3 trials will determine if this therapy might change the current approach to treating newly diagnosed T1DM patients [Tuccinardi D et al. Expert Opin Biol Ther 2011].

Itamar Raz, MD, Hadassah Medical Center, Jerusalem, Israel, reported outcomes from 1 of these trials—a multinational, randomized, double-blind, placebo-controlled, parallel-group study to investigate the clinical Efficacy and Safety of DiaPep277 in Newly Diagnosed Type 1 Diabetes Patients [DIA-AID 1; NCT00615264].

DIA-AID 1 was a 2-year double-blind study conducted in 42 medical centers in 11 countries in Europe, South Africa, and Israel. It included 457 patients aged 16 to 45 years with newly diagnosed T1D (<3 months) and residual β-cell function fasting C-peptide ≥0.22 nmol/L.

The peptide DiaPep227 is an immunodominant epitope of heat shock protein 60 that is found in insulin secretory granules of β cells. It is thought to be an autoantigen and induces T regulatory cells via toll-like receptors [Gupta S. Med Clin N Am 2012].

Patients were randomized 1:1 to receive a total of 9 injections of either 1 mg DiaPep277 or placebo administered quarterly at a medical center. The primary outcome was the change in stimulated C-peptide area under the curve (AUC) from baseline to Month 24 as measured by a 20-minute glucagon-stimulated test. Secondary outcomes included the change in stimulated C-peptide AUC from baseline to Month 24 as measured by the mixed-meal tolerance test (MMTT), the proportion of patients who maintained HbA1C levels ≤7% at the end of the study, and the change in fasting C-peptide from baseline to Month 24.

The primary efficacy endpoint in the modified intention-to-treat population (mITT) showed a trend that became significant (p=0.037) at 24 months, with a 23.4% decline in progression in the DiaPep277 group versus placebo. The difference was even more pronounced in the per-protocol (PP) population, with a relative treatment effect of 29.2% (p=0.011).

Among the secondary endpoints, there was no significant difference between the placebo and treatment groups in change in stimulated C-peptide AUC from baseline to Month 24 as measured by the MMTT. Although there was a trend toward a treatment effect in the change from baseline in fasting C-peptide, the difference between the treatment and placebo groups was not significant.

A significantly greater number of treated patients in the mITT population maintained HbA1C levels ≤7% at the end of the study versus those who received placebo (p=0.03), with an even greater difference between the 2 groups in the PP population (p=0.0082). The number of patients with at least 1 treatment emergent adverse advent (TEAE) was 173 (76.9%) in the DiaPep277 group and 164 (71%) in the placebo group. The number of patients with at least 1 life-threatening TEAE was the same for both groups (2; 0.9%). The most common TEAEs were nasopharyngitis, influenza, upper respiratory tract infection, gastroenteritis, headache, pyrexia, and back pain.

Outcomes from a continuous glucose monitoring substudy conducted on 78 patients at 17 sites showed a significantly lower number of hyperglycemic excursions per patient (defined by glucose levels >140 mg/dL) in the DiaPep277-treated group compared with those who received the placebo (11.5 vs 14.4; p=0.032). In the treated group, the duration of hypoglycemia was shorter and the magnitude of the events showed a strong trend of less severity.

• © 2012 MD Conference Express®