E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Growth hormone deficiency |
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E.1.1.1 | Medical condition in easily understood language |
Growth Hormone Deficiency |
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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 |
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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 |
Evaluate the safety of somavaratan during long-term treatment |
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E.2.2 | Secondary objectives of the trial |
To evaluate changes in pharmacodynamic responses (IGF-I and IGFBP-3), auxologic factors (height, weight, BMI, bone age, height velocity, and height standard deviation scores), metabolic parameters, pubertal development, and anti-drug antibody responses during long-term somavaratan treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria for Subjects Completing a Previous Somavaratan Study: 1. Completion of a somavaratan clinical study in pediatric subjects with GHD. 2. Willing and able to comply with all study procedures. 3. Legally authorized representatives must be willing and able to give informed consent.
Inclusion Criteria for New Treatment Naïve Subjects 1. Chronological Age ≥ 3.0 years. 2. Pre-pubertal status: Absent breast development in girls, testicular volume < 4.0 mL in boys. 3. Diagnosis of GHD as documented by two or more GH stimulation test results ≤ 10.0 ng/mL. The use of prior GH stimulation test results is permitted providing the stimulatory agents, GH assay and test results are approved in writing by the medical monitor. In localities with different diagnostic criteria, any child meeting the GH stimulation test criteria described here will be considered eligible. 4. Normal thyroid function at Screening Visit in subjects not being treated for hypothyroidism. Subjects requiring thyroxine replacement must be considered adequately treated by the PI and Medical Monitor. 5. Normal adrenal function (morning cortisol and/or local stimulation test) at Screening Visit or within 6 months of the Screening Visit, in subjects not being treated for adrenal insufficiency. Subjects with adrenal insufficiency must receive glucocorticoid treatment for a minimum of 4 weeks before study drug administration. 6. Pathology relating to cause of GHD must be stable for at least 6 months prior to screening. 7. Legally authorized representatives must be willing and able to give informed consent.
Inclusion Criteria for Subjects Transitioning from Daily rhGH (Switch Subjects) 1. Subjects with GHD (diagnosed according to the current consensus guidelines) who are receiving treatment with daily rhGH. 2. Chronological Age ≥ 3.0 years. 3. Pre-pubertal status: Absent breast development in girls, testicular volume < 4.0 mL in boys. 4. Normal thyroid function at Screening Visit in subjects not being treated for hypothyroidism. Subjects requiring thyroxine replacement must be considered adequately treated by the PI and Medical Monitor. 5. Normal adrenal function (morning cortisol and/or local stimulation test) at Screening Visit or within 6 months of the Screening Visit, in subjects not being treated for adrenal insufficiency. Subjects with adrenal insufficiency must receive glucocorticoid treatment for a minimum of 4 weeks before study drug administration. 6. Pathology relating to cause of GHD must be stable for at least 6 months prior to screening. 7. Willingness to discontinue daily rhGH therapy. 8. Legally authorized representatives must be willing and able to give informed consent. |
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E.4 | Principal exclusion criteria |
Exclusion Criteria for all Subjects: 1. Withdrawal from a somavaratan clinical study in pediatric subjects with GHD. 2. Current, significant disease (e.g., diabetes, cystic fibrosis, renal insufficiency). In all cases of concurrent disease, screening must be approved in writing by the medical monitor. 3. Chromosomal aneuploidy, significant gene mutations (other than those that cause GHD) or confirmed diagnosis of a named syndrome (e.g., Russell Silver, Prader Willi, Turner, etc.). Unconfirmed or suspected genetic variants will be considered individually. 4. Birth weight and/or birth length less than 5th percentile for gestational age using gestational age growth charts. 5. Prolonged daily (>14 days) use of anti-inflammatory doses of oral glucocorticoids. 6. Prior history of malignancy. 7. Treatment with an investigational drug in the 30 days prior to screening. 8. Known allergy to constituents of the study drug formulation. 9. Ocular findings suggestive of increased intracranial pressure and/or retinopathy at screening. 10. Significant spinal abnormalities including scoliosis, kyphosis, Chiari malformation, and spina bifida variants. 11. Significant abnormality in screening studies (as assessed by PI and medical monitor). 12. Current social conditions which would prevent completion of study activities (e.g., planned family move to a distant location). 13. History of pancreatitis or undiagnosed chronic abdominal pain. 14. History of spinal or total body irradiation. 15. Other pituitary hormone deficiencies that are not properly treated. 16. Unwillingness to provide consent for participation in all trial activities. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety as assessed by physical examination, inspection of injection sites, vital signs, clinical laboratory determinations (including fasting glucose, insulin, and lipids), 12-lead ECGs (for new treatment naïve subjects and subjects not previously exposed to somavaratan), PK/PD assessments, and immunogenicity assessments. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary growth endpoints are the annual assessment of height velocity, changes in height SDS, body weight, body mass index, bone age and pubertal status. Secondary PD endpoints include changes in IGF-I and IGFBP-3 expressed as concentrations and/or SD scores. These secondary endpoints may be further evaluated to determine potential differences in response due to age and gender, baseline conditions, as well as other measures.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 30 |
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 |
Poland |
Sweden |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |