E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Juvenile idiopathic arthritis (JIA) and nephrotic syndrome (NeS)
|
|
E.1.1.1 | Medical condition in easily understood language |
Inflammatory disorder of joints and kidney disorder |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of long-term treatment with Genotonorm on linear growth in children with short stature receiving steroid therapy |
|
E.2.2 | Secondary objectives of the trial |
To assess the effect of long term treatment with Genotonorm on bone mineralization.
To assess the effect of long term treatment with Genotonorm on body composition.
To assess safety (clinically and biologically eg glucose and lipid metabolism).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Children with JIA or NeS,
2. Chronological age (CA) (greater than)> 3 years old,
3. Before or during puberty,
4. Treated with corticoids for at least 1 year at a dose greater than equal to (>=) 0.2 mg/kg/day equivalent prednisone, IV or orally, daily or alternate day regimen, and were intending to continue corticotherapy with hGH treatment,
5. Height less than (<) -2 standard deviation (SD) or loss of 1 SD during the 2 years preceding inclusion in the study,
6. Bone age (BA) <13 years for females and; <14 years for males,
7. In pubertal subjects B2 ≤breast development less than equal to (<=) B3 for females and 4 ml <= testicular volume <= 12 ml for males,
8. Provided signed informed consent.
|
|
E.4 | Principal exclusion criteria |
1. Diabetes Type 1 and 2,
2. Endocrine disease, except well substituted hypothyroidism,
3. Chronic renal diseases with glomerular filtration rate <50 ml/min/1.73 m2,
4. Known or suspected allergy to the preservative m-cresol, Non compliant subjects,
5. Subjects treated with sexual steroids (estrogens, testosterone) during the 6 months before inclusion in the study,
6. Secondary resistance to the treatment of NeS defined by proteinuria with albuminemia <30 grams per liter (g/l) for >3 consecutive months,
7. Malignancies,
8. Previous human growth hormone (hGH) treatment,
9. Inclusion in other study protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Change From Baseline in Height Standard Deviation Score According to Chronological Age (SDS/CA) at Year 3
2) Change From Baseline in Height Standard Deviation Score According to Chronological Age (SDS/CA) at Final Height
3) Change From Baseline in Weight Standard Deviation Score (SDS) at Final Height
4) Puberty Stage at Final Height |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Baseline, Year 3
2) Baseline, when final height was reached (assessed up to Year 11)
3) Baseline, when final height was reached (assessed up to Year 11)
4) When final height was reached (assessed up to Year 11) |
|
E.5.2 | Secondary end point(s) |
1) Bone Age
2) Lean Body Mass
3) Annual Percent Change in Lean Body Mass at Year 1, 2 and 3
4) Percent Change From Baseline in Lean Body Mass at Year 3
5) Lean Body Mass as Percentage of Total Weight
6) Lean Body Mass Standard Deviation Score According to Chronological Age (SDS/CA)
7) Fat Mass
8) Annual Percent Change in Fat Mass at Year 1, 2 and 3
9) Percent Change From Baseline in Fat Mass at Year 3
10) Fat Mass as Percentage of Total Weight
Baseline
11) Fat Mass Standard Deviation Score According to Chronological Age (SDS/CA)
12) Apparent Bone Mineral Density of Lumbar Spine (BMAD [LS])
13) Apparent Bone Mineral Density Standard Deviation Score of Lumbar Spine According to Chronological Age (BMAD [LS] [SDS/CA])
14) Apparent Bone Mineral Density Standard Deviation Score of Lumber Spine According to Tanner Puberty Stage (BMAD [LS] [SDS/Tanner Puberty Stage])
15) Bone Mineral Density of Total Body (BMD [TB])
16) Bone Mineral Density of Lumbar Spine (BMD [LS])
17) Bone Mineral Content of Total Body (BMC [TB])
18) Annual Percent Change in Bone Mineral Content of Total Body (BMC [TB]) at Year 1, 2 and 3
19) Percent Change From Baseline in Bone Mineral Content of Total Body (BMC [TB]) at Year 3
20) Bone Mineral Content Standard Deviation Score of Total Body According to Chronological Age (BMC [TB] [SDS/CA])
21) Bone Mineral Content Standard Deviation Score of Total Body According to Tanner Puberty Stage (BMC [TB] [SDS/Tanner Puberty Stage])
Timepoints for Secondary endpoints number 15-21 listed here:
15) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
16) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
17) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
18) Baseline, Year 1, 2, 3
19) Baseline, Year 3
20) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
21) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
2) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
3) Baseline, Year 1, 2, 3
4) Baseline, Year 3
5) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
6) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
7) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
8) Baseline, Year 1, 2, 3
9) Baseline, Year 3
10)Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
11) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
12) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
13) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
14) Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11
|
|
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 | 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.8.3 |
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 | No |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 29 |