E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
growth hormone deficiency (GHD) in children |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056438 |
E.1.2 | Term | Growth hormone deficiency |
|
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 determine safety and tolerability of single subcutaneous (sc) doses of pegylated long-acting human growth hormone (NNC126-0083) compared to 7 days treatment with sc doses of Norditropin NordiFlex® in growth hormone deficient (GHD) children
|
|
E.2.2 | Secondary objectives of the trial |
To determine pharmacokinetics (PK) and pharmacodynamics (PD) of single sc doses of NNC126-0083 compared to 7 days treatment with sc doses of Norditropin NordiFlex® in GHD children. To compare local tolerability (i.e. injection site reactions) of single sc doses of NNC126-0083 compared to 7 days treatment with sc doses of Norditropin NordiFlex® in GHD children
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 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 GHD child.) 2. Confirmed diagnosis of growth hormone insufficiency as defined by two different GH provocation tests, defined as a peak of GH level < 7 ng/mL. For children with three or more pituitary hormone deficiency only one GH provocation test will be needed. If in accordance with country specific practice growth hormone insufficiency can be defined by only one GH provocation test, defined as a peak of GH level < 7 ng/mL. 3. Pre-pubertal children. 4. Boys: Age ≥ 6 year and ≤ 12 years. Girls: Age ≥ 6 year and ≤ 12 years. 5. Body weight ≥ 16 kg. 6. GH replacement treatment ≥ 3 month.
All GHD children will be required to discontinue GH replacement treatment 7 days (+2days) prior to NNC126-0083 and Norditropin NordiFlex® administration.
|
|
E.4 | Principal exclusion criteria |
1. Known or suspected allergy to trial product(s) or related products. 2. Previous participation (randomisation) in this trial. 3. Participation in any other clinical trial involving any investigational products within the last three months prior to this trial. 4. Evidence of tumour growth or malignant disease. 5. GHD children with overt diabetes mellitus (fasting blood glucose > 7 mmol/l (126 mg/dL)). 6. GHD children with a history of previous hypoglycaemic episode(s) after cessation of GH treatment. 7. Known chromosomal abnormalities and medical “syndromes” (Turner syndrome, Laron syndrome, Noonan syndrome or absence of growth hormone receptors). 8. Congenital abnormalities (causing skeletal abnormalities), Russell-Silver Syndrome, skeletal dysplasias. 9. Poorly controlled or uncontrolled pituitary insufficiencies of other axes (e.g., thyroid-stimulating hormone, adrenocorticotropic hormone/cortisol, vasopressin deficiency): Children who are on stable replacement therapy for less than 3 months for other hormonal deficiencies prior to enrolment. 10. Major medical conditions and/or presence of contraindication to GH treatment. 11. History of any illnesses or disease that, in the opinion of the Investigator might confound the results of the trial or pose additional risk in administering the trial product to the GHD child 12. Clinically significant illness within 4 weeks of dosing. 13. Any clinically significant abnormal haematology or biochemistry screening tests, as judged by the Investigator. 14. Active hepatitis B, measured by surface antigen B (HbsAg) and/or active hepatitis C, measured by positive hepatitis C virus antibody test. 15. Clinically significant abnormal ECG at screening as evaluated by Investigator. 16. Surgery or trauma with significant blood loss within the last 3 months prior to dosing. 17. Mental incapacity of the child, parents/legal guardian or language barriers which preclude adequate understanding or cooperation, who are unwilling to participate in the trial or who in the opinion of their general practitioner or the Investigator should not participate in the trial. 18. The GHD child and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct. 19. Any condition interfering with trial participation or evaluation or that may be hazardous to the GHD child.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Adverse Events • Clinical laboratory safety (haematology, biochemistry and urinalysis) • Fasting glucose • Fasting insulin • Physical examination • Vital signs • Body weight • ECG • Local tolerability • NNC126-0083 antibodies • Human Growth hormone antibodies
|
|
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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
open-labelled, single dose, dose-escalation, sequential dose group trial |
|
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.8.3 |
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.8.4.1 | 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 | 14 |
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 | Information not present in EudraCT |
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 |
|
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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 18 |