CSI-Glucagon for Prevention of Hypoglycemia in Children With Congenital Hyperinsulinism
Condition: Congenital Hyperinsulinism
MeSH terms: Congenital Hyperinsulinism; Nesidioblastosis; Hypoglycemia; Hyperinsulinism
Intervention: Glucagon; Placebo
Intervention description: Room-temperature-stable, non-aqueous injectable liquid formulation of synthetic glucagon peptide; Isotonic saline
Intervention MeSH terms: Glucagon; Glucagon-Like Peptide 1
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Maximum age: 12 Months
Healthy volunteers: No
Keywords: hypoglycemia

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosed with hyperinsulinism:

             a. Biochemical; detectable insulin (i.e., ≥1 µIU/L) at time of hypoglycemia (i.e,
             blood glucose <50 mg/dl), and/or suppressed free fatty acids (FFA), and/or suppressed
             beta-hydroxybutyrate (BOHB) and/or glycemic response to glucagon at time of
             hypoglycemia.

          2. Absolute necessity of intravenous glucose to prevent hypoglycemia:

               1. Having failed diazoxide therapy as defined by inadequacy of 5 days maximum dose
                  of diazoxide to eliminate the need for IV glucose, not necessarily that diazoxide
                  has no effect.

               2. May be on diazoxide and/or octreotide, but these drugs will be weaned off prior
                  to randomization.

               3. May be on dextrose feeds.

          3. Patient may be a participant in other study protocols such as observational studies,
             as long as no investigational intervention has taken place within 24 hrs. prior to
             screening.

          4. Less than 12 months of age at screening.

        Exclusion Criteria:

          1. History of allergy to glucagon or excipients in the CSI-Glucagon formulation.

          2. Currently receiving, or less than 12 hours removed from IV glucagon treatment that
             resulted in a best achievable GIR > 8 mg/(kg*min), prior to the start of study drug.

          3. Diazoxide naïve or within five days of starting diazoxide.

          4. Receiving steroids at doses larger than 20 mg/m2/day (hydrocortisone equivalent).

          5. Patients with sepsis.

          6. Receiving alpha or beta agonists for blood pressure support.

          7. Received an investigational or other study drug within 5 half-lives of drug.

          8. Body weight less than or equal to 2.3 kg/5.0 lbs.

          9. History of pancreatectomy and GIR < 8 mg/(kg*min) after weaning of all concomitant
             therapies.