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

NCT03667053 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ZP4207-17086
• Study Type: interventional
• Target: 42
• Locations: 3 countries
• Sites: 5

Brief Summary

A phase 3, randomized, double-blind, placebo- and active-controlled, parallel-arm trial to assess the efficacy, safety, and pharmacokinetics of dasiglucagon relative to placebo and GlucaGen® when administered as a rescue therapy for severe hypoglycemia in children with type 1 diabetes mellitus (T1DM) treated with insulin

Conditions

Hypoglycemia

Keywords

Glucagon; Dasiglucagon

Outcome Measures

Primary Outcomes (1)

• Time to Plasma Glucose Recovery

  Plasma glucose recovery was defined as first increase in plasma glucose of ≥20 mg/dL (1.1 mmol/L) from baseline during the hypoglycemic clamp procedure without administration of rescue intravenous (IV) glucose. Patients who received rescue IV glucose before 45 minutes and patients not recovering within 45 minutes after dosing were censored at 45 minutes. Time to plasma glucose recovery was summarized for each treatment group using Kaplan Meier (KM) estimates together with the 95% confidence interval. Note that the upper confidence limit for the placebo median was not estimable, but is set to 45 minutes (censored value) here.

  0-45 minutes after dosing

Secondary Outcomes (15)

• Plasma Glucose Recovery

  0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

• Plasma Glucose Changes From Baseline

  0-30 minutes after dosing: assessed at 10, 15, 20 and 30 minutes after study drug injection

• Pharmacodynamics - Area Under the Effect Curve (0-30 Minutes)

  0-30 minutes

• Administration of Rescue IV Glucose Infusion After IMP Injection

  0-45 minutes

• Time to First IV Glucose Infusion After IMP Administration

  0-45 minutes

Study Arms (3)

dasiglucagon

EXPERIMENTAL

Single fixed dose (s.c.injection) of dasiglucagon

Drug: dasiglucagon

placebo

PLACEBO COMPARATOR

Single fixed dose (s.c.injection) of placebo

Drug: placebo

GlucaGen®

ACTIVE COMPARATOR

Single fixed dose (s.c.injection) of GlucaGen®

Drug: GlucaGen HypoKit

Interventions

dasiglucagon DRUG

glucagon analog

Also known as: ZP4207

dasiglucagon

placebo DRUG

placebo for dasiglucagon

Also known as: placebo for dasiglucagon

placebo

GlucaGen HypoKit DRUG

native glucagon

GlucaGen®

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• Female or male patients with T1DM for at least 1 year, diagnostic criteria as defined by the American Diabetes Association; and receiving daily insulin
• At least 6.0 years of age (inclusive) and less than 18.0 years
• Body weight ≥20 kg
• 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
• 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
• Willingness to adhere to the protocol requirements

You may not qualify if:

• \. 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

Sponsors & Collaborators

• Zealand Pharma: lead

Study Sites (5)

AMCR Institute, Inc

Escondido, California, 92025, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Indiana University, Department of Pediatrics

Indianapolis, Indiana, 46202, United States

Location

Auf der Bult - Diabetes Center for Children

Hanover, 30173, Germany

Location

University Medical Center Ljubljana, Children's Hospital, Department for Endocrinology, Diabetes and Metabolism

Ljubljana, 1000, Slovenia

Location

MeSH Terms

Conditions

Hypoglycemia

Interventions

dasiglucagon

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr Kim Mark Knudsen
• Organization: Zealand Pharma A/S

KMKnudsen@zealandpharma.com

+4550603780

Study Officials

• Christina M Sylvest, MSc Pharm

  Zealand Pharma A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 12, 2018
• Study Start: September 28, 2018
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: June 30, 2021
• Results First Posted: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); DE (1); SL (1)