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

Primary Purpose

Hypoglycemia, Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
dasiglucagon
GlucaGen
Sponsored by
Zealand Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoglycemia focused on measuring Glucagon, Dasiglucagon

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Compass Research
  • Advanced Clinical Research
  • CRC - Clinical Research Center, Medizinische Universität Graz
  • LMC Manna Research
  • LMC Calgary
  • LMC Diabetes & Manna Research
  • Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

dasiglucagon (ZP4207)

GlucaGen

Arm Description

Repeated single fixed doses (s.c.injection) of dasiglucagon

Repeated single fixed doses (s.c.injection) of GlucaGen

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
Characterization of ADA Response - Neutralizing Activity
Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies.
Characterization of ADA Response - Titer of Neutralizing Activity
Titre of neutralizing activity of ADA positive patients. ADA = antidrug antibodies.
Characterization of ADA Response - Cross-reactivity
Percentage of ADA positive patients with cross-reactivity towards endogenous glucagon. ADA = antidrug antibodies.
Characterization of ADA Response - Timing
The timing of detected ADA response. ADA = antidrug antibodies.
Characterization of ADA Response - Duration
The Duration of detected ADA response. ADA = antidrug antibodies.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 7, 2017
Last Updated
April 8, 2021
Sponsor
Zealand Pharma
Collaborators
SynteractHCR
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1. Study Identification

Unique Protocol Identification Number
NCT03216226
Brief Title
A Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen in Patients With Type 1 Diabetes Mellitus
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
June 28, 2017 (Actual)
Primary Completion Date
February 13, 2018 (Actual)
Study Completion Date
February 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand Pharma
Collaborators
SynteractHCR

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoglycemia, Diabetes Mellitus, Type 1
Keywords
Glucagon, Dasiglucagon

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
dasiglucagon (ZP4207)
Arm Type
Experimental
Arm Description
Repeated single fixed doses (s.c.injection) of dasiglucagon
Arm Title
GlucaGen
Arm Type
Experimental
Arm Description
Repeated single fixed doses (s.c.injection) of GlucaGen
Intervention Type
Drug
Intervention Name(s)
dasiglucagon
Other Intervention Name(s)
ZP4207
Intervention Description
Glucagon Analog
Intervention Type
Drug
Intervention Name(s)
GlucaGen
Other Intervention Name(s)
GlucaGen HypoKit
Intervention Description
Native Glucagon
Primary Outcome Measure Information:
Title
Percentage of Patients With ADA
Description
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.
Time Frame
104 days after the first dose
Secondary Outcome Measure Information:
Title
Percentage of Patients With Treatment-induced ADA
Description
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
Time Frame
104 days after the first dose
Title
Percentage of Patients With Treatment-boosted ADA
Description
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
Time Frame
104 days after the first dose
Title
Characterization of ADA Response - Neutralizing Activity
Description
Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies.
Time Frame
104 days after the first dose
Title
Characterization of ADA Response - Titer of Neutralizing Activity
Description
Titre of neutralizing activity of ADA positive patients. ADA = antidrug antibodies.
Time Frame
104 days after the first dose
Title
Characterization of ADA Response - Cross-reactivity
Description
Percentage of ADA positive patients with cross-reactivity towards endogenous glucagon. ADA = antidrug antibodies.
Time Frame
104 days after the first dose
Title
Characterization of ADA Response - Timing
Description
The timing of detected ADA response. ADA = antidrug antibodies.
Time Frame
104 days after the first dose
Title
Characterization of ADA Response - Duration
Description
The Duration of detected ADA response. ADA = antidrug antibodies.
Time Frame
104 days after the first dose
Title
Pharmacokinetics - Area Under the Plasma Concentration Curve
Description
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.
Time Frame
0-30 minutes
Title
Pharmacokinetics - Area Under the Plasma Concentration Curve
Description
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.
Time Frame
0-90 minutes
Title
Pharmacokinetics - Maximum Plasma Concentration
Description
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.
Time Frame
90 minutes
Title
Pharmacokinetics - Time to Maximum Plasma Concentration
Description
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.
Time Frame
90 minutes
Title
Pharmacodynamics - Area Under the Effect Curve
Description
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.
Time Frame
0-30 minutes
Title
Pharmacodynamics - Area Under the Effect Curve
Description
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.
Time Frame
0-90 minutes
Title
Pharmacodynamics - Change From Baseline Plasma Glucose
Description
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.
Time Frame
90 minutes
Title
Pharmacodynamics - Time to Maximum Plasma Glucose Concentration
Description
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.
Time Frame
90 minutes
Title
Pharmacodynamics - An Increase in the Plasma Glucose Concentration of ≥20 mg/dL Within 30 Minutes After Treatment
Description
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.
Time Frame
30 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina Sylvest, MSc Pharm
Organizational Affiliation
Zealand Pharma A/S
Official's Role
Study Director
Facility Information:
Facility Name
Compass Research
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Advanced Clinical Research
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
CRC - Clinical Research Center, Medizinische Universität Graz
City
Graz
Country
Austria
Facility Name
LMC Manna Research
City
Barrie
Country
Canada
Facility Name
LMC Calgary
City
Calgary
Country
Canada
Facility Name
LMC Diabetes & Manna Research
City
Toronto
Country
Canada
Facility Name
Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin
City
Hamburg
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

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

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