E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the immunogenicity of repeated single doses of dasiglucagon and GlucaGen following subcutaneous (s.c.) administration compared with s.c. GlucaGen in T1DM patients. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to evaluate the safety, tolerability and pharmacodynamic response of repeated single doses of dasiglucagon following s.c. administration compared with s.c. GlucaGen in T1DM patients. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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)
|
|
E.4 | Principal exclusion criteria |
3. History of anaphylaxis or symptoms of severe systemic allergy (such as angioedema) 6. Patients on a closed loop artificial pancreas 8. Active malignancy within the last 5 years 9. Congestive heart failure, New York Heart Association class II-IV 10. Inadequately treated blood pressure as defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥90 mmHg at screening 11. Current bleeding disorder, including use of anticoagulant treatment 12. Known presence or history of pheochromocytoma (i.e. adrenal gland tumor) or insulinoma (i.e. insulin-secreting pancreas tumor) 13. Known or suspected HIV infection 14. Use of a systemic beta-blocker drug, indomethacin, warfarin or anticholinergic drugs in the previous 28 days before Day 1 of this trial 15. Use of systemic corticosteroids, anti-inflammatory biological agents, kinase inhibitors or other immune modulating agents within the last 3 months prior to screening 16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 X the upper limit of normal (ULN), bilirubin >1.5 X ULN, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) Study definition. Altered electrolytes values of clinical relevance for cardiac conduction, as judged by the investigator. 17. Clinically significant abnormal ECG at screening as evaluated by Investigator 19. 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. 23. Use of prescription or non-prescription medications known to cause QT prolongation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall ADA incidence This will be calculated as a percentage of the combined results of treatment-induced ADA-positive patients and treatment-boosted ADA-positive patients and the total number of evaluable patients, excluding baseline-positive patients without any samples available after drug administration.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 7(Day 104 of the follow-up period; EoT visit) |
|
E.5.2 | Secondary end point(s) |
• Treatment-induced ADA Incidence calculated as a percentage of the total number of evaluable patients that were ADA negative at baseline and ADA positive after drug administration and the total number of evaluable patients, excluding baseline positive patients without any samples available after drug administration. • Treatment-boosted ADA Incidence calculated as percentage of baseline ADA-positive patients with significant increases (≥5-fold) in ADA titer after drug administration and the total number of evaluable patients, excluding baseline-positive patients without any samples available after drug administration.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 7(Day 104 of the follow-up period; EoT visit) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Canada |
Germany |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |