E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children with congenital hyperinsulinism |
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E.1.1.1 | Medical condition in easily understood language |
Childrens with hereditary high level of insulin |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 | 10061211 |
E.1.2 | Term | Hyperinsulinism |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of dasiglucagon administered as a subcutaneous
(SC) infusion in reducing hypoglycemia in children with Congenital
Hyperinsulinism. |
|
E.2.2 | Secondary objectives of the trial |
-To evaluate the safety and tolerability of dasiglucagon administered as an SC infusion in children with CHI
-To evaluate the efficacy of dasiglucagon in reducing glucose requirements
-To investigate quality of life and resource utilization |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Established and documented diagnosis of CHI based on standard of care.
2. Male or female between 3 months and 12 years of age (both inclusive) at screening
3. Has a negative serum pregnancy test at screening/baseline (only for girls of childbearing potential)
4. Sexually active female patients (and their partners) must continue to use acceptable contraception or refrain from sexual activity from screening until 30 days after the last dose of trial drug. Females must abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception. Abstinence can only be
accepted if this is true abstinence in line with the preferred and usual lifestyle of the patient.
Acceptable methods of contraception are:
a) Hormonal contraceptives (e.g., oral contraceptive pill, depot, patch, intramuscular implant or injection, sponge, or vaginal ring), stabilized for at least 30 days if first use
or
b) Barrier method, e.g., (i) condom (male or female) and (ii) diaphragm with spermicide
Germany: Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence.
5. Experiencing ≥3 events of hypoglycemia per week (PG <70 mg/dL [<3.9 mmol/L]) according to the investigator's evaluation
6. Following receipt of oral and written information about the trial, the patient (depending on local IRB/IEC requirements) must provide assent and one or both parents* or guardians of the patient must provide
signed informed consent before any trial-related activity is carried out. France, Germany, Israel: The consent must correspond to the patient's presumed will where such a will can be ascertained.
7. Previously undergone near-total pancreatectomy or being treated with a non-surgical approach, having been evaluated as not eligible for pancreatic surgery
8. If somatostatin analogues or sirolimus are used, the therapy should be well established as judged by the investigator, especially when considering their biological half-life
* If required by local regulations, both parents must give their permission unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child. |
|
E.4 | Principal exclusion criteria |
1.Previous administration of dasiglucagon (previously referred to as ZP4207)
2. Known or suspected allergy to the trial drug or related products
3. Previous participation (randomization) in this trial
4. Circulatory instability requiring supportive medication or presence of pheochromocytoma. United Kingdom: Presence of hypertension or hypotension, including circulatory instability requiring supportive medication or presence of pheochromocytoma
5. Requires exogenous insulin
6. Body weight of <4 kg (8.8 lbs.)
7. Documented HbA1c ≥7% subsequent to near-total pancreatectomy and within 6 months prior to screening
8. Known or suspected presence of significant central nervous system disease/injury such that in the investigator's opinion will affect trial participation
9. Use of systemic corticosteroids, e.g., hydrocortisone >20 mg/mg/m2 body surface area or equivalent in the 5 days before screening
10. Use of anti-inflammatory biological agents, or other immunemodulating agents in the 3 months prior to screening
11. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 X the upper limit of normal (ULN), or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 adjusted by a pediatric formula (e.g., Schwartz formula)
12. Any clinically significant abnormality identified on echocardiogram that in the opinion of the investigator would affect the patient's ability to participate in the trial
13. History of laboratory test results obtained before screening that show presence of HIV, hepatitis B surface antigen, hepatitis C antibody, or hepatitis A immunoglobulin M
14. Any recognized clotting or bleeding disorders.
15. Has participated in an interventional clinical trial (investigational or marketed product) within 3 months of screening or 5 half-lives of the drug under investigation (whichever comes first), or plans to participate
in another clinical trial.
16. The use of prescription or non-prescription medications known to
cause QT prolongation.
Randomization Exclusion Criteria:
1. Use of glucagon within 24 hours before randomization
2. Significant changes to CHI medications during screening
3. An average of <3 events per week of hypoglycemia, as recorded in the diary during the 2 weeks prior to randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
Treatment Period 1: Hypoglycemia event rate, defined as average weekly
number of hypoglycemic events (PG <70 mg/dL or 3.9 mmol/L) during
Weeks 2-4, as detected by self-monitored PG (SMPG). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Treatment Period 1
- Increase in fasting tolerance (time from beginning of meal to the beginning of the first continuous 15-minute Continuous glucose monitoring [CGM] reading <70 mg/dL [3.9 mmol/L].
-Total amount of gastric carbohydrates administered (via nasogastric [NG] tube or gastrostomy) per week to treat hypoglycemia during Weeks 2-4.
- CGM percent time in range 70-180 mg/dL (3.9-10.0 mmol/L) during Weeks 2-4.
- Clinically significant hypoglycemia event rates, defined as average weekly number of events < 54 mg/dL (3.0 mmol/L) as detected by SMPG during Weeks 2-4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Period 1: Randomised (Test drug versus SoC). Period 2: Open-label (Test drug and SoC) |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Germany |
Israel |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |