Clinical trial NCT03216226: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypoglycemia
Diabetes Mellitus, Type 1
Keywords: Glucagon
Dasiglucagon
Lead sponsor: Zealand Pharma
Sponsor class: INDUSTRY
Collaborators: name: SynteractHCR
First posted: 2017-07-13
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Patients With ADA
timeFrame: 104 days after the first dose
Secondary outcomes:
measure: Percentage of Patients With Treatment-induced ADA
timeFrame: 104 days after the first dose
measure: Percentage of Patients With Treatment-boosted ADA
timeFrame: 104 days after the first dose
measure: Characterization of ADA Response - Neutralizing Activity
timeFrame: 104 days after the first dose
measure: Characterization of ADA Response - Titer of Neutralizing Activity
timeFrame: 104 days after the first dose
measure: Characterization of ADA Response - Cross-reactivity
timeFrame: 104 days after the first dose
measure: Characterization of ADA Response - Timing
timeFrame: 104 days after the first dose
measure: Characterization of ADA Response - Duration
timeFrame: 104 days after the first dose
measure: Pharmacokinetics - Area Under the Plasma Concentration Curve
timeFrame: 0-30 minutes
measure: Pharmacokinetics - Area Under the Plasma Concentration Curve
timeFrame: 0-90 minutes
measure: Pharmacokinetics - Maximum Plasma Concentration
timeFrame: 90 minutes
measure: Pharmacokinetics - Time to Maximum Plasma Concentration
timeFrame: 90 minutes
measure: Pharmacodynamics - Area Under the Effect Curve
timeFrame: 0-30 minutes
measure: Pharmacodynamics - Area Under the Effect Curve
timeFrame: 0-90 minutes
measure: Pharmacodynamics - Change From Baseline Plasma Glucose
timeFrame: 90 minutes
measure: Pharmacodynamics - Time to Maximum Plasma Glucose Concentration
timeFrame: 90 minutes
measure: Pharmacodynamics - An Increase in the Plasma Glucose Concentration of ≥20 mg/dL Within 30 Minutes After Treatment
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Graz
country: Austria
facility: CRC - Clinical Research Center, Medizinische Universität Graz
city: Barrie
country: Canada
facility: LMC Manna Research
city: Calgary
country: Canada
facility: LMC Calgary
city: Toronto
country: Canada
facility: LMC Diabetes & Manna Research
city: Hamburg
country: Germany
facility: Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin
Study officials:
affiliation: Zealand Pharma A/S
name: Christina Sylvest, MSc Pharm
role: STUDY_DIRECTOR
References: