This study is a randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of dasiglucagon in children between the ages of 7 days and 12 months who have congenital hyperinsulinism. Dasiglucagon will be given as a subcutaneous infusion while patients are admitted to the hospital. Other treatments for hyperinsulinism may be changed as allowed while maintaining safe blood sugar levels. For the second part of the study, patients may be able to go home on the medication.

Our team at the Congenital Hyperinsulinism Center at CHOP is working on a research study to determine whether an experimental gene therapy product, DTX401, is safe and effective in people with glycogen storage disease type Ia (GSDIa). The FDA has not approved this drug for the treatment of GSDIa but has approved us to use this drug as part of this clinical trial. The purpose of this research study is to see if DTX401 can help people with GSDIa have normal blood sugar levels and fewer episodes of hypoglycemia. DTX041 works by delivering copies of the G6PC gene to your liver through a one-time infusion. Participation in this study will last for 2 years and will involve 30 study visits. It is possible that treatment with the study drug infusion may improve your blood sugar levels. Travel costs will be covered by the study and you will receive compensation for participating.

The purpose of this study is to look at the safety and tolerability (how well you will react) of the study drug (HM15136) and to determine if it is effective for the treatment of Congenital Hyperinsulinism (HI). HM15136 is an experimental drug which is not approved by the FDA for the treatment of HI. HM15136 is stable and has a long effect in the body, only requiring it to be given (by injection) once a week. HM15136 is designed to act like glucagon, a hormone produced by the pancreas that helps the body maintain normal blood sugar levels by increasing the glucose produced in the liver and breaking down glycogen (a form of stored glucose) into the usable glucose form.

Participation lasts for up to 22 weeks and will involve up to 13 study visits. Study procedures include taking the study drug for 8 weeks, having electrocardiograms, wearing a continuous glucose monitor (CGM) and using a handheld glucose meter, having blood and urine tests, and completing an electronic diary.

The main risks of this study include: nausea, vomiting, diarrhea, abdominal pain, injection site reactions (swelling, itching, bleeding, or pain), loss of appetite, weight loss, high blood sugar. You may benefit if the study drug proves to be more effective than your current treatment plan in treating low blood sugar.

Our team is working on a clinical drug trial that involves giving you a study drug that is not FDA-approved called RZ358. The goal of the trial is to test the study drug safety, how your body processes the drug, how the drug affects your body, and see if it can increase your blood sugar. If you agree to take part, your participation will last for up to 27 weeks and include 4 weeks of screening, 8 weeks of treatment, and a 15 week follow-up period. It is possible that treatment with the study drug infusions may improve your blood sugar levels and/or reduce the use of other medication(s) to prevent hypoglycemia. For more information, contact us at HIResearch@email.chop.edu.

This clinical trial is for patients with congenital hyperinsulinism (HI) who are experiencing low blood sugar on their current treatment. The purpose of this study is to find out if the study drug, named RZ358, helps improve blood sugar levels compared to current HI treatments. RZ358 is an experimental drug which the FDA has approved for use in this clinical trial, but it has not approved the study drug to be given outside of clinical research testing. The study drug is a specialized protein (called a monoclonal antibody) meant to decrease the effect insulin has on lowering blood sugar.

Participation will last for up to 33 weeks or up to 3 years overall for subjects who would like to join the open-label extension phase. This includes a 5-week Screening Period, a Treatment Period that lasts 24 weeks, and then either an 8-week Follow-up Period or a 2-year Extension Period where participants can continue to receive the study drug. Individuals do not need to participate in the 2-year extension part of the study to take part in the treatment and monitoring period. During the treatment period, participants will be given the study drug or a placebo. A placebo is an inactive substance used to compare how well the study drug works. Only study drug and not placebo is given during the extension period.

Participants in this trial will:

• Receive the study drug or a placebo 7 times during the treatment period
• Receive the study drug for up to 2 years in the optional extension period
• Have electrocardiograms (ECGs)
• Have ultrasounds of their liver
• Wear a continuous glucose monitor (CGM) and take fingerstick glucose checks
• Have research blood tests
• Complete study diaries and surveys

The main risks of this study are from the study drug. These include infusion reactions (redness, tenderness, irritation at the infusion site), headaches, dizziness, hypoglycemia (low blood sugar), upper respiratory infections (colds), and excess body hair growth. Participants may benefit if the study drug proves to be more effective than current HI medications.