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

NCT ID: NCT02937558

Last Updated: 2019-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2018-10-31

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 Description

This is a Phase 2, multi-center, randomized, placebo-controlled, double-blind (DB) 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 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.

Conditions

Congenital Hyperinsulinism

Keywords

hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

CSI-Glucagon (Double-Blind Phase - 2 days)

Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr.

Group Type: EXPERIMENTAL

Glucagon

Intervention Type: DRUG

Room-temperature-stable, non-aqueous injectable liquid formulation of synthetic glucagon peptide

Placebo (Double-Blind Phase - 2 days)

Vehicle solution delivered as a 24-hour continuous subcutaneous infusion via a patch pump.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Isotonic saline

CSI-Glucagon (Open-label Phase - Up to 28 days)

Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr.

Group Type: EXPERIMENTAL

Glucagon

Intervention Type: DRUG

Room-temperature-stable, non-aqueous injectable liquid formulation of synthetic glucagon peptide

Interventions

Glucagon

Room-temperature-stable, non-aqueous injectable liquid formulation of synthetic glucagon peptide

Intervention Type: DRUG

Placebo

Isotonic saline

Intervention Type: OTHER

Other Intervention Names

CSI-Glucagon (continuous subcutaneous glucagon infusion)

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.

• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Xeris Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCLA Mattel Children's Hospital

Los Angeles, California, United States

UCSF School of Medicine, Division of Pediatric Endocrinology

San Francisco, California, United States

Washington University, St. Louis Children's Hospital

St Louis, Missouri, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine, Texas Children's Hospital

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R44DK105691-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

XSGO-CH01

Identifier Type: -

Identifier Source: org_study_id