A Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen in Patients With Type 1 Diabetes Mellitus

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Parallel Group Safety Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen® Administered Subcutaneously in Patients With Type 1 Diabetes Mellitus (T1DM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03216226
• Other study ID #: ZP4207-16136
• Status: Completed
• Phase: Phase 3
• Start date: June 28, 2017
• Est. completion date: February 13, 2018

Study information

• Verified date: April 2021
• Source: Zealand Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial's objective is to evaluate the immunogenicity of repeated single doses of dasiglucagon* and GlucaGen following subcutaneous (SC) administration in patients with type 1 diabetes mellitus (T1DM) and further to evaluate the safety and tolerability of dasiglucagon and GlucaGen.

*dasiglucagon is the proposed International Nonproprietary Name (pINN) for ZP4207

Description:

Patients with T1DM were randomly assigned in a 1:1 ratio to receive 3 SC injections of either dasiglucagon (0.6 mg) or GlucaGen (1 mg), with 1 week between doses. Patients were followed for 15 weeks from the day of the first dose to assess the immune response. Patients with previous exogenic glucagon exposure were not excluded from the trial, but the information on previous glucagon administration was recorded to enable subgroup analyses. It was expected that 112 patients in total would be randomly assigned to treatment groups and treated. A total of 90 patients were expected to complete the trial (45 in each treatment arm). To qualify as completed, the patient had to be dosed according to the procedure described in the protocol and to have blood drawn for the antidrug antibody analyses as scheduled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: February 13, 2018
• Est. primary completion date: February 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient)

• Availability for the entire trial period

• Age between 18 and 70 years, both inclusive

• Male or female patients with T1DM for at least 1 year. Diagnostic criteria as defined by the American Diabetes Association

• Hemoglobin A1c (HbA1c) <10%

• Stable anti-diabetic treatment for at least 1 month (e.g. within 10% insulin dose adjustment)

Exclusion Criteria:

• Previous administration of dasiglucagon (previously referred to as ZP4207)

• Known or suspected allergy to trial medication(s) or related products

• History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema)

• Previous participation (randomization) in this trial

• Females who are pregnant according to a positive pregnancy test, actively attempting to get pregnant, or are lactating

• Patients on a closed loop artificial pancreas

• Receipt of any investigational drug within 3 months prior to screening

• Active malignancy within the last 5 years

• Congestive heart failure, New York Heart Association class II-IV

• Inadequately treated blood pressure as defined as systolic blood pressure =160 mmHg or diastolic blood pressure =90 mmHg at screening

• Current bleeding disorder, including use of anticoagulant treatment

• Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin-secreting pancreas tumor)

• Known or suspected HIV infection

• Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial

• Use of systemic corticosteroids, anti-inflammatory biological agents, kinase inhibitors or other immune modulating agents within the last 3 months prior to screening

• Donation of blood or plasma in the past month, or in excess of 500 mL within 12 weeks prior to screening

• A positive result in the alcohol and/or urine drug screen at the screening visit. Significant history of alcoholism or drug abuse as judged by the investigator or consuming more than 24 g alcohol per day for men, or more than 12 g alcohol per day for women.

• Surgery or trauma with significant blood loss within the last 2 months prior to screening

• Use of prescription or non-prescription medications known to cause QT prolongation

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• dasiglucagon
Glucagon Analog
• GlucaGen
Native Glucagon

Locations

Country	Name	City	State
Austria	CRC - Clinical Research Center, Medizinische Universität Graz	Graz
Canada	LMC Manna Research	Barrie
Canada	LMC Calgary	Calgary
Canada	LMC Diabetes & Manna Research	Toronto
Germany	Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin	Hamburg
United States	Advanced Clinical Research	Meridian	Idaho
United States	Compass Research	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Zealand Pharma	SynteractHCR

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With ADA	Percentage of the combined results of treatment-induced ADA-positive patients and treatment-boosted ADA-positive patients out of the total number of evaluable patients. ADA = antidrug antibodies.	104 days after the first dose
Secondary	Percentage of Patients With Treatment-induced ADA	Percentage of the total number of evaluable patients that were ADA negative at baseline and ADA positive after drug administration out of the total number of evaluable patients. ADA = antidrug antibodies	104 days after the first dose
Secondary	Percentage of Patients With Treatment-boosted ADA	Percentage of baseline ADA-positive patients with significant increases (=5-fold) in ADA titre after drug administration out of the total number of evaluable patients. ADA = antidrug antibodies	104 days after the first dose
Secondary	Characterization of ADA Response - Neutralizing Activity	Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies.	104 days after the first dose
Secondary	Characterization of ADA Response - Titer of Neutralizing Activity	Titre of neutralizing activity of ADA positive patients. ADA = antidrug antibodies.	104 days after the first dose
Secondary	Characterization of ADA Response - Cross-reactivity	Percentage of ADA positive patients with cross-reactivity towards endogenous glucagon. ADA = antidrug antibodies.	104 days after the first dose
Secondary	Characterization of ADA Response - Timing	The timing of detected ADA response. ADA = antidrug antibodies.	104 days after the first dose
Secondary	Characterization of ADA Response - Duration	The Duration of detected ADA response. ADA = antidrug antibodies.	104 days after the first dose
Secondary	Pharmacokinetics - Area Under the Plasma Concentration Curve	Area under the plasma concentration curve (AUC) 0-30 minutes at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10 and 30 minutes after dosing.	0-30 minutes
Secondary	Pharmacokinetics - Area Under the Plasma Concentration Curve	Area under the plasma concentration curve (AUC) 0-90 minutes at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	0-90 minutes
Secondary	Pharmacokinetics - Maximum Plasma Concentration	Maximum plasma concentration (Cmax) at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	90 minutes
Secondary	Pharmacokinetics - Time to Maximum Plasma Concentration	Time to maximum plasma concentration (Tmax) at visit 2 and 4 (days 0 and 14). Plasma PK concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	90 minutes
Secondary	Pharmacodynamics - Area Under the Effect Curve	Plasma glucose profiles, area under the effect curve (AUE) 0-30 minutes at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10 and 30 minutes after dosing.	0-30 minutes
Secondary	Pharmacodynamics - Area Under the Effect Curve	Plasma glucose profiles, area under the effect curve (AUE) 0-90 minutes at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	0-90 minutes
Secondary	Pharmacodynamics - Change From Baseline Plasma Glucose	Change from baseline plasma glucose to maximum plasma glucose (CEmax) at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	90 minutes
Secondary	Pharmacodynamics - Time to Maximum Plasma Glucose Concentration	Time to maximum plasma glucose concentration (Tmax) at visit 2 and 4 (days 0 and 14). Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	90 minutes
Secondary	Pharmacodynamics - An Increase in the Plasma Glucose Concentration of =20 mg/dL Within 30 Minutes After Treatment	An increase in the plasma glucose concentration of =20 mg/dL within 30 minutes after treatment at visit 2 and visit 4. Plasma glucose concentrations were measured before dosing and at 5, 10, 30, 60 and 90 minutes after dosing.	30 minutes