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

Primary Purpose

Congenital Hyperinsulinism

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Glucagon

Placebo

About this trial

This is an interventional prevention trial for Congenital Hyperinsulinism focused on measuring hypoglycemia

Eligibility Criteria

undefined - 12 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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.
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.
Less than 12 months of age at screening.

Exclusion Criteria:

History of allergy to glucagon or excipients in the CSI-Glucagon formulation.
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.
Diazoxide naïve or within five days of starting diazoxide.
Receiving steroids at doses larger than 20 mg/m2/day (hydrocortisone equivalent).
Patients with sepsis.
Receiving alpha or beta agonists for blood pressure support.
Received an investigational or other study drug within 5 half-lives of drug.
Body weight less than or equal to 2.3 kg/5.0 lbs.
History of pancreatectomy and GIR < 8 mg/(kg*min) after weaning of all concomitant therapies.

Sites / Locations

UCLA Mattel Children's Hospital
UCSF School of Medicine, Division of Pediatric Endocrinology
Washington University, St. Louis Children's Hospital
Cook Children's Medical Center
Baylor College of Medicine, Texas Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

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

Placebo (Double-Blind Phase - 2 days)

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

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Number of Subjects With Clinically Meaningful Reduction in Glucose Infusion Rate (Double-Blind)

Change 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 a decrease in GIR ≥ 20% at 24 hours, and ≥ 33% at 48 hours will be considered to have had a clinically meaningful treatment response.

Secondary Outcome Measures

Percent Change in GIR (Double-Blind)

The groups will be compared for mean percent change in GIR from baseline to the end of the double-blind study phase.

Number of Subjects With Clinically Meaningful Reduction in Glucose Infusion Rate (Open-Label)

Change from baseline in glucose infusion rate (GIR) will be determined for each subject at the end of open-label treatment. Subjects with a decrease in GIR ≥ 33% will be considered to have had a clinically meaningful treatment response.

Percent Change in Glucose Infusion Rate (Open-Label)

The groups will be compared for mean percent change in GIR from baseline to the end of the open-label study phase.

Full Information

NCT ID

NCT02937558

First Posted

October 14, 2016

Last Updated

November 25, 2019

Sponsor

Xeris Pharmaceuticals

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02937558

Brief Title

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

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 Age With Congenital Hyperinsulinism

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

October 2016 (undefined)

Primary Completion Date

September 2018 (Actual)

Study Completion Date

October 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Xeris Pharmaceuticals

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Congenital Hyperinsulinism

Keywords

hypoglycemia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo (Double-Blind Phase - 2 days)

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Glucagon

Other Intervention Name(s)

CSI-Glucagon (continuous subcutaneous glucagon infusion)

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Isotonic saline

Primary Outcome Measure Information:

Title

Number of Subjects With Clinically Meaningful Reduction in Glucose Infusion Rate (Double-Blind)

Description

Time Frame

Baseline to end of blinded treatment at 24 or 48 hours

Secondary Outcome Measure Information:

Title

Percent Change in GIR (Double-Blind)

Description

The groups will be compared for mean percent change in GIR from baseline to the end of the double-blind study phase.

Time Frame

Baseline to the end of blinded treatment at 24 or 48 hours

Title

Number of Subjects With Clinically Meaningful Reduction in Glucose Infusion Rate (Open-Label)

Description

Time Frame

Baseline to the end of open-label treatment at 72 hours

Title

Percent Change in Glucose Infusion Rate (Open-Label)

Description

The groups will be compared for mean percent change in GIR from baseline to the end of the open-label study phase.

Time Frame

Baseline to end of treatment at 72 hours

10. Eligibility

Sex

All

Maximum Age & Unit of Time

12 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Absolute necessity of intravenous glucose to prevent hypoglycemia: 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. May be on diazoxide and/or octreotide, but these drugs will be weaned off prior to randomization. May be on dextrose feeds. 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. Less than 12 months of age at screening. Exclusion Criteria: History of allergy to glucagon or excipients in the CSI-Glucagon formulation. 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. Diazoxide naïve or within five days of starting diazoxide. Receiving steroids at doses larger than 20 mg/m2/day (hydrocortisone equivalent). Patients with sepsis. Receiving alpha or beta agonists for blood pressure support. Received an investigational or other study drug within 5 half-lives of drug. Body weight less than or equal to 2.3 kg/5.0 lbs. History of pancreatectomy and GIR < 8 mg/(kg*min) after weaning of all concomitant therapies.

Facility Information:

Facility Name

UCLA Mattel Children's Hospital

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

UCSF School of Medicine, Division of Pediatric Endocrinology

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

Washington University, St. Louis Children's Hospital

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63130

Country

United States

Facility Name

Cook Children's Medical Center

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104

Country

United States

Facility Name

Baylor College of Medicine, Texas Children's Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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