E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth hormone deficiency |
|
E.1.1.1 | Medical condition in easily understood language |
Growth Hormone Deficiency |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
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 | 10056438 |
E.1.2 | Term | Growth hormone deficiency |
E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
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 |
Compare the safety and efficacy of subcutaneous VRS-317 and daily rhGH during 12 months of treatment. |
|
E.2.2 | Secondary objectives of the trial |
Evaluate and compare changes in pharmacodynamic responses (IGF-I, IGF binding protein-3 (IGFBP-3), growth hormone binding protein (GHBP) and acid labile subunit (ALS)), bone age, weight, body mass index, height standard deviation scores, pubertal development and anti-drug antibody responses. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Chronological Age ≥ 3.0 years and ≤ 10.0 (girls) and ≤ 11.0 (boys). 2. Pre-pubertal status: Absent breast development in girls, testicular volume <4.0 mL in boys. 3. Diagnosis of GHD as documented two or more GH stimulation test results ≤ 10.0 ng/mL. 4. Height SDS ≤ -2.0 at screening. 5. Weight for Stature ≥ 10th percentile. 6. IGF-I SD score ≤ -1.0 at screening. 7. Delayed bone age (≥ 6 months as determined by the central reader). Left hand X-Ray must be obtained within 90 days of screening visit or during screening. 8. Normal thyroid function test results at screening visit (or a minimum of four weeks of thyroxine replacement therapy prior to study drug administration). 9. Available adrenal function test results at screening visit (or in the preceding 6 months) in all subjects without a minimum of four weeks glucocorticoid replacement therapy prior to study drug administration. 10. Pathology relating to cause of GH deficiency must be stable for at least 6 months prior to screening. 11. Legally authorized representatives must be willing and able to give informed consent. |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with any growth promoting agent (e.g., GH, IGF-I, GH releasing hormone (GHRH), gonadotrophins, sex steroids). Up to 10 day exposures to a growth promoting agent for diagnostic purposes are permitted if administered 30 or more days prior to screening. 2. Documented history of, or current, significant disease. 3. Chromosomal aneuploidy, significant gene mutations (other than those that cause GHD) or confirmed diagnosis of a named syndrome. 4. Birth weight and/or birth length less than 5th percentile for gestational age using gestational age growth charts. 5. A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), use of ADHD medications or a likelihood of starting ADHD medications during study participation. 6. Daily use of anti-inflammatory doses of glucocorticoid. 7. Prior history of leukemia, lymphoma, sarcoma or cancer. 8. Treatment with an investigational drug in the 30 days prior to screening. 9. Known allergy to constituents of the study drug formulation. 10. Ocular findings suggestive of increased intracranial pressure and/or retinopathy at screening. 11. Significant spinal abnormalities including scoliosis, kyphosis and spina bifida variants. 12. Significant abnormality in screening laboratory studies. 13. Current social conditions which would prevent completion of study activities (e.g., planned family move to a distant location). 14. History of pancreatitis or undiagnosed chronic abdominal pain. 15. History of spinal or total body irradiation. 16. Subjects with other pituitary hormone deficiency who are not treated properly. 17. Unwillingness to provide consent for participation in all trial activities. 18. Unwillingness to accept dose assignments. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Annual height velocity after 12 months continous treatment with either VRS-317 or daily rhGH. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- IGF-1 and IGFBP-3 responses to study drug administration. - Change in height SDS. - Change in bone age relative to chronological age (BA / CA) - Change in body weight. - Change in body mass index. |
|
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 | 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 | 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 | 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
| 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Belgium |
Canada |
Netherlands |
Poland |
Sweden |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 16 |