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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02937558
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : August 16, 2018
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Xeris Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Congenital Hyperinsulinism Drug: Glucagon Other: Placebo Phase 2

Detailed Description:

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 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : October 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia
Drug Information available for: Glucagon

Arm Intervention/treatment
Experimental: CSI-Glucagon
Glucagon solution delivered as a continuous subcutaneous infusion via a patch pump at a starting dosage of 5 mcg/kg/hr.
Drug: Glucagon
Room-temperature-stable, non-aqueous injectable liquid formulation of synthetic glucagon peptide
Other Name: CSI-Glucagon (continuous subcutaneous glucagon infusion)

Placebo Comparator: Placebo
Vehicle solution delivered as a 24-hour continuous subcutaneous infusion via a patch pump.
Other: Placebo
Isotonic saline

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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).

  4. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02937558

Contact: Martin J Cummins 8062822120
Contact: Debby Powers, RN 512-739-8665

United States, California
UCLA Mattel Children's Hospital Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Tali Homsey    310-794-3326   
Principal Investigator: Steven D Mittelman, MD         
UCSF School of Medicine, Division of Pediatric Endocrinology Recruiting
San Francisco, California, United States, 94143
Contact: Rebecca Wesch    415-476-5984   
Principal Investigator: Srinath Sanda, MD         
United States, Missouri
Washington University, St. Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Gianna Macias   
Contact: Bess Marshall, MD   
Principal Investigator: Bess Marshall, MD         
United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Larry Rodriguez, BSN, RN, CRC    682-885-7208   
Principal Investigator: Paul Thornton, MD         
Baylor College of Medicine, Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Jennifer Abernathy    832-822-4856   
Principal Investigator: Siripoom Mckay, MD         
Sponsors and Collaborators
Xeris Pharmaceuticals
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Responsible Party: Xeris Pharmaceuticals Identifier: NCT02937558     History of Changes
Other Study ID Numbers: XSGO-CH01
1R44DK105691-01 ( U.S. NIH Grant/Contract )
First Posted: October 18, 2016    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Xeris Pharmaceuticals:

Additional relevant MeSH terms:
Congenital Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Infant, Newborn, Diseases
Glucagon-Like Peptide 1
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs