Clinical Trial: CSI-Glucagon for Prevention of Hypoglycemia in Children With Congenital Hyperinsulinism

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2 Proof-of-Concept Study of CSI-Glucagon™ (Continuous Subcutaneous Glucagon Infusion) to Prevent Hypoglycemia With Lower Intravenous Glucose Infusion Rates in Children up to One Year of

Brief Summary: This is a Phase 2, multi-center, randomized, placebo-controlled, double-blind trial with open-label follow-up designed to assess the efficacy of Xeris Glucagon delivered as a continuous subcutaneous infusion to prevent hypoglycemia with lower intravenous glucose infusion rates in children < 1 year of age with congenital hyperinsulinism.

Detailed Summary:

This is a Phase 2, multi-center, randomized, placebo-controlled, double-blind parallel group study with open-label follow-up designed to evaluate the efficacy of CSI-Glucagon™ for the prevention of hypoglycemia with lower IV glucose infusion rates when delivered subcutaneously to patients up to 1 year of age with congenital hyperinsulinism. CSI-Glucagon™ is expected to provide a better inpatient treatment option compared to the current standard of care.

The study will consist of three phases:

  1. Baseline Phase: First is a baseline stabilization phase of at least 24 hours, during which concomitant therapy with octreotide and diazoxide will be safely weaned and continuous enteric feed will be held constant to the degree possible, with the only factors varying being meal size and IV glucose infusion rate (GIR) adjusted by a set plasma glucose measurement driven algorithm.
  2. Blinded, Randomized Treatment Phase: Following the stabilization phase, subjects will be randomly assigned to blinded treatment with either glucagon or placebo, which will be delivered for up to 48 hours with an OmniPod® infusion pump with the controller set to a starting basal rate for glucagon of 5 μg/kg/hr and GIR adjustments used to maintain euglycemia. After 48 hours of blinded treatment, all subjects will transition to open-label active treatment. However, if GIR reduction from baseline is < 20% at 24 hours, subjects will be transitioned early to the open-label phase.
  3. Open-label Treatment Phase: The third study period will involve use of CSI-Glucagon™ to manage blood glucose with minimal GIR for up to 28 days of cumulative exposure.

Sponsor: Xeris Pharmaceuticals

Current Primary Outcome: Reduction in Glucose Infusion Rate [ Time Frame: Baseline to end of treatment at 24 or 48 hours ]

Reduction from baseline in glucose infusion rate (GIR) will be determined for each subject at 24 and 48 hours from the start of blinded treatment. Subjects with GIR ≥ 20% at 24 hours, and ≥ 33% at 48 hours will be considered to have had a positive treatment response.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean Reduction in GIR [ Time Frame: Baseline to the end of treatment at 24 or 48 hours ]
    The groups will be compared for average proportional GIR reduction from baseline.
  • Targeted GIR reduction [ Time Frame: Baseline to the end of treatment at 24 or 48 hours ]
    The groups will be compared for the percentage of subjects that achieve GIR ≤ 8 mg/(kg*min).
  • Targeted carbohydrate reduction [ Time Frame: Baseline to the end of treatment at 24 or 48 hours ]
    The groups will be compared for the percentage of subjects that achieve a daily caloric intake from carbohydrate, combining oral, tube and IV sources, ≤ 8 mg/(kg*min).
  • Time in range [ Time Frame: Baseline to the end of treatment at 24 or 48 hours ]
    The groups will be compared for the proportional time in hypoglycemia, with blood glucose < 70 mg/dL, and in euglycemia, with blood glucose in the range of 70-180 mg/dL.


Original Secondary Outcome: Same as current

Information By: Xeris Pharmaceuticals

Dates:
Date Received: October 14, 2016
Date Started: October 2016
Date Completion: December 2017
Last Updated: November 29, 2016
Last Verified: November 2016