Oral Adjunctive Therapy Yields Positive Results for Adults with Type 1 Diabetes

Positive results have been announced from part 2 of the phase 2 Simplici-T1 trial assessing TTP399 as an oral adjunctive therapy to insulin in adults with type 1 diabetes (T1D).

TTP399 is a novel, once-daily, liver-selective glucokinase activator. Simplici-T1, a multi-center, randomized, 12-week trial, investigated the efficacy and safety of 800 mg of TTP399 compared with placebo in 85 patients with T1D on optimized insulin therapy.

The trial successfully achieved its primary objective, which was analyzed using 2 statistical approaches to evaluating the effect of TTP399. The primary statistical analysis evaluated the effect on long-term blood sugar (HbA1c) regardless of treatment adherence or notable change in insulin administration.

Under the primary statistical analysis, the trial achieved its primary objective by demonstrating statistically significant improvements in HbA1c for TTP399 compared with placebo at week 12.

TTP399 was well tolerated with similar incidences of treatment-emergent adverse events (AEs) overall and by system organ class in both treatment groups. The study had no report of diabetic ketoacidosis in either treatment group. There was no incidence of severe hypoglycemia in the treated group and 1 incident in the placebo group.

Patients taking TTP399 experienced fewer symptomatic hypoglycemic episodes: 2 subjects taking TTP399 reported at least 1 AE compared with 8 subjects taking placebo.

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“I am very pleased that part 2 of the study confirmed the positive results and effects we saw in part 1. A once-a-day pill that reduces HbA1c and improves time in range with continuous glucose monitoring, without increasing hypoglycemia or any signal for [AEs], is a big win for the future care of type 1 diabetes,” John Buse, MD, PhD, director of the North Carolina Translational and Clinical Sciences Institute and principal investigator of the study, said in a press release.

In order to rule out that the reduction of HbA1c was driven by the administration of excess insulin (3 or more units per day), a second statistical analysis was performed. Based on this analysis, patients treated with TTP399 achieved a statistically-significant, placebo-subtracted reduction in HbA1c. Patients taking placebo experienced a 0.11% increase in HbA1c from a mean study baseline HbA1c of 7.6% following a multi-week insulin optimization period prior to the administration of study treatment.

Daily time in range was improved by approximately 2 hours in patients treated with TTP399 relative to placebo (p=0.03). TTP399 treatment reduced the total daily meantime bolus insulin dose by 11% relative to baseline (p=0.02), whereas the placebo-treated group experienced a 3% decrease relative to baseline.

TTP399 selectively activates glucokinase (GK), a key regulator of glucose metabolism in the liver. This activation has been shown to increase glucose utilization, which in turn lowers blood glucose. Simplici-T1 is the first study to test activation of GK in patients with T1D, evaluating daily oral TTP399 as an adjunct to insulin therapy.

Reference

• vTv Therapeutics Announces Positive Results from Part 2 of the Phase 2 Simplici-T1 Study of TTP399, Potential First-in-Class Oral Adjunctive Therapy for Patients with Type 1 Diabetes [news release]. VTV Therapeutics website. Published February 10, 2020. http://ir.vtvtherapeutics.com/news-releases/news-release-details/vtv-therapeutics-announces-positive-results-part-2-phase-2. Accessed February 17, 2020.