Trial to Confirm the Efficacy and Safety of Dasiglucagon in the Treatment of Hypoglycemia in T1DM Children

Trial Purpose and Description

The goal of the study is to demonstrate that study drug (dasiglucagon) is superior to placebo (no medicine) and is comparable to marketed glucagon (Glucagen®) in treating hypoglycemia in children aged ?6 and <18 years with Type 1 Diabetes (T1D). We also want to evaluate safety, efficacy, and pharmacokinetics of dasiglucagon in this subject population. The study design will include recruiting 6 subjects from Yale (total = 40 from all sites) who will be randomized 2:1:1 dasiglucagon:placebo:GlucaGen® during hypoglycemic clamp procedure. Trial assessments will be conducted by blinded study staff and the handling/preparation/administration of treatments will be conducted by unblinded study staff. The visit schedule includes a total of 3 on-site (clinic and hospital) visits over approximately 2 months. The Screening Visit (visit 1) will be used to obtain consent and assess the potential participant's study eligibility, and will be conducted at Yale Children's Diabetes Research Office. The Dosing Visit (visit 2) includes an overnight stay at the Hospital Research Unit (HRU) of Yale New Haven Hospital. The subject will come to the HRU in the evening. They will be screened and, if eligible, be randomly assigned to receive either dasiglucagon, GlucaGen(R), or placebo. They will have two infusion catheters placed (1-glucose infusion; 2-insulin infusion). In the morning a third catheter will be placed (blood sampling). The hypoglycemic clamp will be started. Once the subject's blood sugar drops to a certain level dasiglucagon, GlucaGen®, or placebo will be given to the subject by injection into the belly or thigh. If the subject receives placebo and continues to be in a low blood sugar state, the study doctor will give a rescue treatment with an intravenous glucose solution. 

The last visit will be the Follow-up Visit (visit 3), which be used to assess the subject's health status and test for dasiglucagon and GlucaGen® antibodies. All visits include bloodwork and ECG; one visit will include a hypoglycemic clamp procedure to assess response to drug.

Ages: 6 - 17 years

Gender: Both


Eligibility Criteria

Inclusion Criteria:

  1. Following receipt of verbal and written information about the trial, patient, parent(s) or guardian(s) of the patient must provide signed informed consent before any trial-related activity is carried out
  2. Female or male patients with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association; and receiving daily insulin
  3. At least 6.0 years of age (inclusive) and less than 18.0 years
  4. Body weight ≥20 kg
  5. Female patients must meet one of the following criteria:

    a. Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout the entire duration of the trial from screening until last follow-up visit. An acceptable method of contraception includes at least one of the following: i. Abstinence from heterosexual intercourse ii. Systemic contraceptives (birth control pills, injectable/implant/ insertable hormonal birth control products, transdermal patch); if the participant is using systemic contraceptives, she must use an additional form of acceptable contraception (iii or iv, below) iii. Intrauterine device (with and without hormones) iv. Condom with spermicide or b. Participant is of non-childbearing potential due to pre-puberty status or a medical condition confirmed by the investigator

  6. Male patients must meet the following criteria: If sexually active, uses condom and partner practices contraception during the trial from screening and until last follow-up visit
  7. Willingness to adhere to the protocol requirements

  8. Exclusion Criteria:

1. Females who are pregnant according to a positive urine pregnancy test, actively attempting to get pregnant, or are lactating 2. Known or suspected allergy to trial product(s) or related products 3. History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema) 4. Previous randomization in this trial 5. History of an episode of severe hypoglycemia that required a third party assistance within a month prior to screening visit 6. History of hypoglycemic events associated with seizures or hypoglycemia unawareness in the last year prior to screening 7. History of epilepsy or seizure disorder 8. Receipt of any investigational drug within 3 months prior to screening 9. Active malignancy within the last 5 years 10. Congestive heart failure, New York Heart Association class II-IV 11. Current bleeding disorder, including anti-coagulant treatment 12. Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin secreting pancreas tumor) 13. Use of a daily systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial 14. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × the upper limit of the normal range (ULN), bilirubin >1.5 × ULN, estimated glomerular filtration rate <30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease study definition, or altered electrolyte values of clinical relevance for cardiac conduction, as judged by the investigator 15. Clinically significant abnormal electrocardiogram (ECG) at screening as judged by the investigator 16. Clinically significant illness within 4 weeks before screening, as judged by the investigator 17. Surgery or trauma with significant blood loss within the last 2 months prior to screening 18. Patients with mental incapacity or language barriers which preclude adequate understanding or cooperation, who are unwilling to participate in the trial, or who in the opinion of the investigator should not participate in the trial 19. Any condition interfering with trial participation or evaluation or that could be hazardous to the patient 20. The use of prescription or non-prescription medications known to cause QT prolongation


Zealand Pharma A/S

Start Date: 01/29/2019

End Date: 07/01/2019

Last Updated: 03/25/2019

Study HIC#: 2000024075

Get Involved

For more information about this study, contact:
Kristen Kraemer
+1 631-275-8634
kristen.kraemer@yale.edu

If you would prefer to contact a member of the Help us Discover team about this trial and other similar trials, please email helpusdiscover@yale.edu or call 1-877-978-8348.

Trial Image

Investigators

Eda Cengiz

Principal Investigator

Sub-Investigators