| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Growth hormone deficiency in children |
|
| E.1.1.1 | Medical condition in easily understood language |
| Growth hormone deficiency in children |
|
| 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 |
| To compare efficacy of somapacitan vs Norditropin® on longitudinal growth in Chinese children with GHD |
|
| E.2.2 | Secondary objectives of the trial |
| To compare safety of somapacitan vs Norditropin® in Chinese children with GHD |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Informed consent of parent or legally acceptable representative of subject and child assent, as age-appropriate, must be obtained before any trial-related activities.
•The parent or legally acceptable representative of the child must sign and date the Informed Consent Form (according to local requirements).
• The child must sign and date the child assent form or provide oral assent (if required according to local requirements)
2. Pre-pubertal children:
•Boys:
•Testis volume < 4 ml
•Age ≥ 2 years and 26 weeks and ≤ 11.0 years at the time of signing informed consent.
•Girls:
•Tanner stage 1, for breast development (no palpable glandular breast tissue)
•Age ≥ 2 years and 26 weeks and ≤ 10.0 years at the time of signing informed consent.
3. Confirmed diagnosis of growth hormone deficiency determined by two different GH stimulation tests performed within 12 months prior to screening, defined as a peak growth hormone level of ≤ 10.0 ng/ml using the WHO International Somatropin 98/574 standard.
•If only one GH stimulation test is available before screening, then confirmation of GHD by second and different GH stimulation test must be done.
•For children with at least 2 additional pituitary hormone deficiencies (other than GHD) only one GH stimulation test is needed.
4. Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and gender according to Chinese general population standards at screening.
5. Impaired height velocity defined as annualised height velocity at screening less than 7 cm/year for subjects between 2.5 and 3 years old and less than 5 cm/year for subjects from 3 years and above calculated over a time span of minimum 3 months and maximum 18 months prior to screening according to Chinese guideline and expert consensus on children with short stature and GH therapy.
6. No prior exposure to GH therapy or IGF-I treatment
7. Bone age less than chronological age at screening.
8. Body Mass Index >5th and <95th percentile, body mass index for age growth charts according to the Chinese general population standards.
9. IGF-I < -1.0 SDS at screening, compared to age and gender normalized range measured at central laboratory
10. No intracranial tumour confirmed by magnetic resonance imaging or computer tomography scan. An image or scan taken within 9 months prior to screening can be used as screening data if the medical evaluation and conclusion is available. |
|
| E.4 | Principal exclusion criteria |
1. Known or suspected hypersensitivity to trial products or related products.
2. Previous participation in this trial. Participation is defined as randomisation.
3. Receipt of any investigational medicinal product within 3 months prior to screening or participation in another clinical trial before randomisation
4. Any suspected or known clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements:
•Turner syndrome (including mosaicisms)
•Chromosomal aneuploidy and significant gene mutations causing medical syndromes with short stature, including but not limited to Laron syndrome, Noonan syndrome, Prader-Willi syndrome, abnormal SHOX-1 gene analysis or absence of GH receptors.
•Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
•Congenital abnormalities (causing skeletal abnormalities), including but not limited to Russell-Silver syndrome or skeletal dysplasia.
•Family history of skeletal dysplasia
5. Children born small for gestational age (birth weight 10th percentile of the recommended gender-specific birth weight for gestational age according to national standards in China).
6. Children diagnosed with diabetes mellitus or screening values from central laboratory of
•fasting plasma glucose ≥126 mg/dl (7.0 mmol/L) or
• HbA1c ≥ 6.5%
7. Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening.
8. Children requiring inhaled glucocorticoid therapy at a dose greater than 400 µg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening.
9. Concomitant administration of other treatments that may have an effect on growth, e.g. but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder (ADHD)
10. Diagnosis of attention deficit hyperactivity disorder
11. Prior history or presence of malignancy including intracranial tumors.
12. Prior history or presence of active Hepatitis B or Hepatitis C (exceptions to this exclusion criterion is the presence of antibodies due to vaccination against Hepatitis B).
13. Any clinically significant abnormal laboratory screening tests, as judged by the investigator
14. Any disorder which, in the opinion of the investigator, might jeopardize subject’s safety or compliance with the protocol.
15. The subject or the parent/legally acceptable representative (LAR) is likely to be non-compliant in respect to trial conduct, as judged by the investigator.
16. Children with hypothyroidism and/or adrenal insufficiency not on adequate and stable replacement therapy for at least 90 days prior to randomisation. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Height velocity (annualised) at week 52 |
|
| E.5.2 | Secondary end point(s) |
Efficacy:
1. Change in bone age
2. Change in Height Standard Deviation Score
3. Change in Height Velocity Standard Deviation Score
Safety:
4. Change in fasting plasma glucose
5. Change in HbA1c
Pharmacodynamics
6. Change in IGF-I Standard Deviation Score
7. Change in IGFBP-3 Standard Deviation Score |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From visit 1 to week 52
2.-7. From baseline (week 0) to week 52 |
|
| 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 | 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 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| 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.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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