E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Foetal growth problem
Small for Gestational Age
Growth hormone deficiency in children |
|
E.1.1.1 | Medical condition in easily understood language |
Foetal growth problem
Small for Gestational Age
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 |
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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 |
GHLiquid-1517: To investigate the long-term efficacy as assessed by change in height standard deviation score (SDS) for chronological age (Δ height SDS for chronological age) after treatment in subjects with short stature born small for gestational age (SGA), comparing two doses of NN-220 (0.033 mg/kg/day and 0.067 mg/kg/day).
GHLiquid-1516: To evaluate the efficacy of two doses of NN-220 (0.033 mg/kg/day and 0.067 mg/kg/day) compared to no treatment as assessed by change in height standard deviation score (SDS) for chronological age (delta height SDS for chronological age) from baseline to 52-week treatment in subjects with short stature born small for gestational age (SGA). |
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E.2.2 | Secondary objectives of the trial |
1. To investigate the safety profile of 0.033 mg/kg/day and 0.067 mg/kg/day as assessed by adverse events, clinical laboratory tests, OGTT, HbA1C and bone age.
2. To investigate the growth promoting effect of 0.033 mg/kg/day and 0.067 mg/kg/day as assessed by Δ height velocity SDS for chronological age.
3. To compare the relationship between bone age and height increase of 0.033 mg/kg/day and 0.067 mg/kg/day as assessed by Δ height SDS for bone age.
4. To compare the relationships between concentrations of IGF-I and IGFBP-3 and growth promoting effect of 0.033 mg/kg/day and 0.067 mg/kg/day.
5. To compare the score obtained from questionnaire survey between 0.033 mg/kg/day and 0.067 mg/kg/day.
6. To compare the efficacy of 0.033 mg/kg/day and 0.067 mg/kg/day as assessed by delta height SDS for chronological age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent obtained from each subject’s parent or the subject’s legally acceptable representative before any trial-related activities. If the subject has the agreement ability (as per the Investigator’s or Sub-Investigator’s discretion), informed consent should be also obtained from that subject (Trial-related activities are any procedure that would not have been performed during normal management of the subject.).
2. Subjects who completed GHLiquid-1516
3. Chronological age : boys 4 to < 11 years, girls 4 to < 10 years |
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E.4 | Principal exclusion criteria |
1. Known or suspected allergy to the trial product or related products
2. Subjects with serious heart disease, renal disease or hepatic disease (as judged by the Investigator or Sub-Investigator)
3. Subjects with diabetic type diagnosed with Japanese Diabetes Society Classification (in 1999)
4. Subjects with history or presence of active malignancy
5. Subjects who have been treated with radiotherapy or chemotherapy
6. Subjects who have received systemic administration of following medications within two years prior to Visit 1 (for Subjects in No treatment group in GHLiquid-1516)
− Thyroid hormone, androgen, oestrogen, progesterone, anabolic steroid, adrenocortical steroid (except temporary use), derivative of gonadotropin releasing hormone and somatomedin C
7. Subjects with endocrine diseases which lead to short stature (as judged by the Investigator or Sub-Investigator) (see Appendix E)
8. Subjects with chromosomal abnormalities and malformation syndromes i.e. Turner syndrome, which lead to short stature with exception of Silver-Russell syndrome (as judged by the Investigator or Sub-Investigator) (see Appendix E)
9. Subjects with short stature due to systemic bone diseases such as achondroplasia (as judged by the Investigator or Sub-Investigator) (see Appendix E)
10. Previous participation in this trial (subject who has been registered in this trial previously)
11. Subjects with any condition that the Investigator or Sub-Investigator would judge as not appropriate for trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in height SDS for chronological age (Δ height SDS for chronological age) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to the end of treatment (208 weeks or 260 weeks)
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E.5.2 | Secondary end point(s) |
1. Yearly Height velocity SDS for chronological age - subjects received NN220 treatment for 5 years.
2. Yearly Height velocity SDS for chronological age - subjects received NN220 treatment for 4 years.
3. Change in bone age (left hand X-Ray) at Week 260 - subjects received NN220 treatment for 5 years.
4. Change in bone age (left hand X-Ray) at Week 208 - subjects received NN220 treatment for 4 years.
5. Adverse events - subjects received NN220 treatment for 5 years.
6. Adverse events - subjects received NN220 treatment for 4 years.
(Includes endpoints from main trial GHLiquid-1516) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time frame: Weeks 0-260
2. Time frame: Weeks 0-208
3. Time frame: Week 0, week 260
4. Time frame: Week 0, week 208
5. Time frame: Weeks 0-260
6. Time frame: Weeks 0-208 |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Different doses of the same IMP |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 5 |
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 | 10 |