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| Name | Class |
|---|---|
| SynteractHCR | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dasiglucagon (ZP4207) | Experimental | Repeated single fixed doses (s.c.injection) of dasiglucagon |
|
| GlucaGen | Experimental | Repeated single fixed doses (s.c.injection) of GlucaGen |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dasiglucagon | Drug | Glucagon Analog |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Percentage of Patients With Treatment-boosted ADA |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christina Sylvest, MSc Pharm | Zealand Pharma A/S | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Compass Research | Orlando | Florida | 32806 | United States | ||
| Advanced Clinical Research |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dasiglucagon (ZP4207) | 3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog |
| FG001 | GlucaGen | 3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline characteristics are presented for the patients who were randomized and treated: 111 in total
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| ID | Title | Description |
|---|---|---|
| BG000 | Dasiglucagon (ZP4207) | 3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog |
| BG001 | GlucaGen | 3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Full analysis set of all patients in the safety analysis set (those randomized who received at least 1 dose of trial product) with at least 1 measurement of ADA titres at baseline | Posted | Count of Participants | Participants | 104 days after the first dose |
|
104 days
Adverse events were recorded at each trial visit by the investigator or other designated trial personnel.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dasiglucagon (ZP4207) | 3 repeated doses (s.c.injection) of 0.6 mg dasiglucagon, with 1 week between each dose. dasiglucagon: Glucagon Analog |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kim Mark Knudsen | Zealand Pharma A/S | +45 50603780 | KMKnudsen@zealandpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 21, 2017 | Mar 11, 2021 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 19, 2018 | Mar 11, 2021 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003920 | Diabetes Mellitus |
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| ID | Term |
|---|---|
| C000710373 | dasiglucagon |
| D052216 | Glucagon-Like Peptide 1 |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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| GlucaGen | Drug | Native Glucagon |
|
|
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 |
| Characterization of ADA Response - Neutralizing Activity | Percentage of ADA positive patients with ADA neutralizing activity. ADA = antidrug antibodies. | 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. | 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. | 104 days after the first dose |
| Characterization of ADA Response - Timing | The timing of detected ADA response. ADA = antidrug antibodies. | 104 days after the first dose |
| Characterization of ADA Response - Duration | The Duration of detected ADA response. ADA = antidrug antibodies. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 30 minutes |
| Meridian |
| Idaho |
| 83642 |
| United States |
| CRC - Clinical Research Center, Medizinische Universität Graz | Graz | Austria |
| LMC Manna Research | Barrie | Canada |
| LMC Calgary | Calgary | Canada |
| LMC Diabetes & Manna Research | Toronto | Canada |
| Diabeteszentrum Hamburg West, Gemeinschaftspraxis für Innere Medizin | Hamburg | Germany |
| Patient unable to take time off work to come in for the third injection |
|
| Deviation from protocol window during visit as patient had to leave for work |
|
| Patient withdrawn prior to treatment. Patient veins unsuitable for blood draws |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body weight | Mean | Standard Deviation | kg |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose.
GlucaGen: Native Glucagon
|
|
| 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 | Full analysis set of all patients in the safety analysis set (those randomized who received at least 1 dose of trial product) with at least 1 measurement of ADA titres at baseline | Posted | Count of Participants | Participants | 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 | Full analysis set of all patients in the safety analysis set (those randomized who received at least 1 dose of trial product) with at least 1 measurement of ADA titres at baseline | Posted | Count of Participants | Participants | 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. | No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response. | Posted | 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. | No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of titre of neutralizing activity. | Posted | 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. | No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of cross-reactivity towards endogenous glucagon. | Posted | 104 days after the first dose |
|
|
| Secondary | Characterization of ADA Response - Timing | The timing of detected ADA response. ADA = antidrug antibodies. | No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of timing. | Posted | 104 days after the first dose |
|
|
| Secondary | Characterization of ADA Response - Duration | The Duration of detected ADA response. ADA = antidrug antibodies. | No ADAs were recorded in this trial, therefore it was not possible to characterize the ADA response in terms of duration. | Posted | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Mean | Standard Deviation | h*pmol/L | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Mean | Standard Deviation | h*pmol/L | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Mean | Standard Deviation | pmol/L | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Median | Full Range | hours | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Mean | Standard Deviation | h*mmol/L | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Mean | Standard Deviation | h*mmol/L | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Mean | Standard Deviation | mmol/L | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Median | Full Range | hours | 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. | PK/PD set: all patients in the safety analysis set (patients who were randomized and received at least 1 dose of trial product) with at least 1 pre- and post-dose PK value at 1 visit. PK = pharmacokinetic. PD = pharmacodynamic. | Posted | Count of Participants | Participants | 30 minutes |
|
|
|
| 0 |
| 57 |
| 1 |
| 57 |
| 42 |
| 57 |
| EG001 | GlucaGen | 3 repeated doses (s.c.injection) of 1.0 mg GlucaGen, with 1 week between each dose. GlucaGen: Native Glucagon | 0 | 54 | 0 | 54 | 43 | 54 |
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Retinopathy | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
Not provided
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| Day 14 |
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| Day 14 |
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| Day 14 |
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| Day 14 |
|
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| Day 14 |
|
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| Day 14 |
|
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| Day 14 |
|
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| Day 14 |
|
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| No |
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| Day 14 |
|
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