| 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 |
Cohort I:
To evaluate the efficacy of multiple dose regimens of once-weekly
NNC0195-0092 after 26 weeks of treatment in GH treatment naïve prepubertal
children with GHD compared to once-daily hGH administration
(Norditropin® FlexPro®)
Cohort II and III:
To evaluate the safety of once-weekly NNC0195-0092 during up to 208
weeks of treatment in children with GHD. |
|
| E.2.2 | Secondary objectives of the trial |
Cohort I:
• To evaluate the safety of multiple dose regimens of once-weekly
NNC0195-0092 during 26 weeks of treatment in GH treatment naïve prepubertal
children with GHD.
• To evaluate the efficacy and safety of multiple dose regimens of onceweekly
NNC0195- 0092 for up to 364 weeks of treatment in GH
treatment naïve pre-pubertal children with GHD compared to
Norditropin® FlexPro®.
• To investigate the impact of NNC0195-0092 relative to Norditropin®
FlexPro® on wellbeing, psychosocial functioning and treatment
satisfaction in GH treatment naïve prepubertal children with GHD.
• To monitor NNC0195-0092 and Norditropin® PK throughout the trial. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Cohort I:
• Pre-pubertal children
- Boys: Tanner stage 1 for pubic hair and testis volume < 4 ml, age ≥ 2
years and 26 weeks and ≤ 10.0 years at screening
- Girls: Tanner stage 1 for breast development (no palpable glandular
breast tissue) and pubic hair, age ≥ 2 years and 26 weeks and ≤ 9.0
years at screening
• Confirmed diagnosis of GHD within 12 months prior to screening as
determined by two different GH stimulation tests, defined as a peak GH
level of ≤7.0 ng/ml. For children with three or more pituitary hormone
deficiencies only one GH stimulation test is needed.
• No prior exposure to GH therapy and/or IGF-I (insulin-like growth
factor I) treatment.
• Height of at least 2.0 standard deviations below the mean height for
chronological age (CA) and gender according to the standards of Centers
for Disease Control and Prevention 2-20 years: Girls/Boys stature-forage
and weight-for-age percentiles CDC at screening.
• Annualized height velocity (HV) at screening below the 25th percentile
for CA and gender or below -0.7 SD score for CA and sex, according to
the standards of Prader calculated over a time span of minimum 6
months and maximum 18 months prior to screening.
Cohort II:
- < 2 years and 26 weeks and a minimum weight of 5 kg at screening.
- Confirmed diagnosis of GHD, the GHD diagnosis must be confirmed by
investigator according to local practice.
- For GH treatment naïve subjects, no prior exposure to GH therapy
and/or IGF-I treatment.
- For GH treatment naïve subjects, IGF-I SDS < -1.0 at screening,
compared to age and sex normalized range according to central
laboratory measurements.
Cohort III:
Age:
- Girls: > 9.0 years and ≤ 17.0 years at screening.
- Boys: > 10.0 years and ≤ 17.0 years at screening.
- Confirmed diagnosis of GHD:
a) for GH treatment naïve subjects, confirmed diagnosis within 12
months prior to screening as determined by two different GH stimulation
tests, defined as a peak GH level of ≤ 7.0 ng/ml. For children with three
or more pituitary hormone deficiencies only one GH stimulation test is
needed.
b) for non-GH treatment naïve subjects, confirmed GHD diagnosis by
investigator according to local practice
- For GH treatment naïve subjects, no prior exposure to GH therapy
and/or IGF-I treatment.
- Open epiphyses; defined as bone age < 14 years for females and bone
age < 16 years for males. |
|
| E.4 | Principal exclusion criteria |
Cohort I, II and III:
• Any clinically significant abnormality likely to affect growth or the
ability to evaluate growth with standing/length measurements:
- Chromosomal aneuploidy and significant gene mutations causing
medical "syndromes" with short stature, including but not limited to
Turner syndrome, Laron syndrome, Noonan syndrome, or absence of GH
receptors.
- Congenital abnormalities (causing skeletal abnormalities), including
but not limited to Russell-Silver Syndrome, skeletal dysplasias.
- Significant spinal abnormalities including but not limited to scoliosis,
kyphosis and spina bifida variants.
• Children born small for gestational age (SGA - birth weight and/or
birth length < -2 SD for gestational age).
• Concomitant administration of other treatments that may have an
effect on growth, including but not limited to methylphenidate for
treatment of attention deficit hyperactivity disorder (ADHD).
• Prior history or presence of malignancy and/or intracranial tumour. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Cohort I:
Height velocity (HV) (cm/year) during first 26 week of treatment,
measured as standing height with stadiometer
Cohort II and III:
Incidence of adverse events, including injection site reactions in children
with GHD. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cohort I:
At baseline and after 26 weeks
Cohort II and III:
During at least 13 weeks and up to 208 weeks of treatment |
|
| E.5.2 | Secondary end point(s) |
Cohort I:
Efficacy
Changes in the following variables will be used to address the primary
objective:
1. Height standard deviation score (SDS)
2. HV SDS
Safety
The following endpoints will be used to support the secondary objectives
of evaluation of safety:
3. Incidence of adverse events, including injection site reactions
4. Occurrence of anti-NNC0195-0092 and anti-hGH antibodies |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. + 2.: From baseline to end of main trial period (week 26)
3. + 4.: up to 364 weeks of treatment |
|
| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| 3 treatment periods, 2 controlled and 1 where all patients receive once-weekly trial drug |
|
| 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 | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 |
| Brazil |
| India |
| Israel |
| Japan |
| United States |
| European Union |
| Turkey |
| Ukraine |
|
| 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 | 8 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 3 |
| E.8.9.2 | In all countries concerned by the trial years | 8 |
| 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 | 3 |
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