HypoglycemiaPhase 3NCT03216226
A Trial to Evaluate the Immunogenicity of Dasiglucagon and GlucaGen in Patients With Type 1 Diabetes Mellitus
A Phase 3 study testing dasiglucagon and GlucaGen in people with Hypoglycemia and Diabetes Mellitus, Type 1, run by Zealand Pharma at 7 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hypoglycemia, Diabetes Mellitus, Type 1
- What is being tested?
- dasiglucagon and GlucaGen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 28 Jun 2017to 13 Feb 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Canada3 sites
LMC Manna Research
Barrie
LMC Calgary
Calgary
LMC Diabetes & Manna Research
Toronto
United States2 sites
Advanced Clinical Research
Meridian, Idaho, 83642
Compass Research
Orlando, Florida, 32806
Austria1 site
CRC - Clinical Research Center, Medizinische Universität Graz
Graz
Germany1 site
Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin
Hamburg
About this study
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)
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
Read the 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.
- Conditions
- Hypoglycemia, Diabetes Mellitus, Type 1
- Being tested
- dasiglucagon, GlucaGen
- Keywords
- Glucagon, Dasiglucagon
- Medical subject headings
- Hypoglycemia, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dasiglucagonDrug
Also called ZP4207
Glucagon Analog
GlucaGenDrug
Also called GlucaGen HypoKit
Native Glucagon
| Study group | Role | What they receive |
|---|---|---|
| dasiglucagon (ZP4207) | Experimental | Repeated single fixed doses (s.c.injection) of dasiglucagon Receives: Drug: dasiglucagon |
| GlucaGen | Experimental | Repeated single fixed doses (s.c.injection) of GlucaGen Receives: Drug: GlucaGen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 104 days after the first dose
Secondary outcomes (16)
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
Measured: 104 days after the first dose
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
Measured: 104 days after the first dose
Characterization of ADA Response - Neutralizing Activity
Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies.
Measured: 104 days after the first dose
Characterization of ADA Response - Titer of Neutralizing Activity
Titre of neutralizing activity of ADA positive patients. ADA = antidrug antibodies.
Measured: 104 days after the first dose
Characterization of ADA Response - Cross-reactivity
Percentage of ADA positive patients with cross-reactivity towards endogenous glucagon. ADA = antidrug antibodies.
Measured: 104 days after the first dose
Characterization of ADA Response - Timing
The timing of detected ADA response. ADA = antidrug antibodies.
Measured: 104 days after the first dose
Characterization of ADA Response - Duration
The Duration of detected ADA response. ADA = antidrug antibodies.
Measured: 104 days after the first dose
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.
Measured: 0-30 minutes
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.
Measured: 0-90 minutes
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.
Measured: 90 minutes
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.
Measured: 90 minutes
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.
Measured: 0-30 minutes
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.
Measured: 0-90 minutes
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.
Measured: 90 minutes
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.
Measured: 90 minutes
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.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2017
- Study start28 Jun 2017
- Primary completion13 Feb 2018
- Study completion13 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zealand Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SynteractHCR
- Responsible party
- Sponsor
- Investigators
- Christina Sylvest, MSc Pharm, Study director, Zealand Pharma A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03216226
- Sponsor's protocol ID
- ZP4207-16136
- Status last verified
- Apr 2021
- First submitted
- 7 Jul 2017
- Last updated
- 4 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03216226
- Acronym / sponsor ID
- ZP4207-16136
- Conditions
- Hypoglycemia, Diabetes Mellitus, Type 1
- Keywords
- Glucagon, Dasiglucagon
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Zealand PharmaIndustry (pharma, biotech, devices)
- Collaborators
- SynteractHCR
- Study start
- 28 Jun 2017 (actual)
- Primary completion
- 13 Feb 2018 (actual)
- Study completion
- 13 Feb 2018 (actual)
- First posted
- 13 Jul 2017 (actual)
- Results
- Posted 16 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dasiglucagon (ZP4207) | Experimental | Drug: dasiglucagonRepeated single fixed doses (s.c.injection) of dasiglucagon |
| GlucaGen | Experimental | Drug: GlucaGenRepeated single fixed doses (s.c.injection) of GlucaGen |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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%
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dasiglucagonAlso: ZP4207Glucagon Analog | Drug | dasiglucagon (ZP4207) |
| GlucaGenAlso: GlucaGen HypoKitNative Glucagon | Drug | GlucaGen |
Primary outcome
Percentage of Patients With ADA
Time frame: 104 days after the first dose
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.
16 secondary outcomes
Percentage of Patients With Treatment-induced ADA
Time frame: 104 days after the first dose
Percentage of Patients With Treatment-boosted ADA
Time frame: 104 days after the first dose
Characterization of ADA Response - Neutralizing Activity
Time frame: 104 days after the first dose
Characterization of ADA Response - Titer of Neutralizing Activity
Time frame: 104 days after the first dose
Characterization of ADA Response - Cross-reactivity
Time frame: 104 days after the first dose
Characterization of ADA Response - Timing
Time frame: 104 days after the first dose
Characterization of ADA Response - Duration
Time frame: 104 days after the first dose
Pharmacokinetics - Area Under the Plasma Concentration Curve
Time frame: 0-30 minutes
Pharmacokinetics - Area Under the Plasma Concentration Curve
Time frame: 0-90 minutes
Pharmacokinetics - Maximum Plasma Concentration
Time frame: 90 minutes
Pharmacokinetics - Time to Maximum Plasma Concentration
Time frame: 90 minutes
Pharmacodynamics - Area Under the Effect Curve
Time frame: 0-30 minutes
Pharmacodynamics - Area Under the Effect Curve
Time frame: 0-90 minutes
Pharmacodynamics - Change From Baseline Plasma Glucose
Time frame: 90 minutes
Pharmacodynamics - Time to Maximum Plasma Glucose Concentration
Time frame: 90 minutes
Pharmacodynamics - An Increase in the Plasma Glucose Concentration of ≥20 mg/dL Within 30 Minutes After Treatment
Time frame: 30 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christina Sylvest, MSc Pharm study director
Zealand Pharma A/S
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing dasiglucagon and GlucaGen in people with Hypoglycemia and Diabetes Mellitus, Type 1, run by Zealand Pharma at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada, United States, Austria, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With ADA (time frame: 104 days after the first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2021.