A trial investigating efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in pre-pubertal children with growth hormone deficiency previously untreated with growth hormone

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2015-000531-32-AT
• Date of registration: 03/11/2015
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A trial investigating efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in pre-pubertal children with growth hormone deficiency previously untreated with growth hormone
• Scientific title: A randomised, multinational, active-controlled,(open-labelled), dose finding, (double-blinded), parallel group trial investigating efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in growth hormone treatment naïve pre-pubertal children with growth hormone deficiency
• Date of first enrolment: 10/12/2015
• Target sample size: 75
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000531-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: 3 treatment periods, 2 controlled and 1 where all patients receive once-weekly trial drug; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Brazil, European Union, Germany, India, Israel, Japan, Slovenia, Sweden, Turkey, Ukraine, United States

Contacts

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

Key inclusion & exclusion criteria

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 years and = 17 years at screening.
- Boys: > 10 years and = 17 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 75
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 (not applicable to non-GH treatment naïve subjects in
cohort II and III), including but not limited to methylphenidate for
treatment of attention deficit hyperactivity disorder (ADHD).
• Prior history or presence of malignancy and/or intracranial tumour.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Growth hormone deficiency in children
MedDRA version: 20.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Code: NNC0195-0092 5 mg/1.5 ml PDS290-10
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: 1338578-34-9
Other descriptive name: NNC0195-0092
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.3-

Product Code: NNC0195-0092 10 mg/1.5 ml PDS290-10
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: 1338578-34-9
Other descriptive name: NNC0195-0092
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6.7-

Product Code: NNC0195-0092 15 mg/1.5 ml PDS290-15
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: 1338578-34-9
Other descriptive name: NNC0195-0092
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Norditropin FlexPro 10 mg/1.5 ml
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Somatropin
CAS Number: 12629-01-5
Other descriptive name: SOMATROPIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6.7-

Primary Outcome(s)

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

Main Objective: 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 at least 13
weeks and up to 208
weeks of treatment in children with GHD.

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.

Secondary Objective: 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.

Secondary Outcome(s)

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

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

Secondary ID(s)

NN8640-4172

Source(s) of Monetary Support

Novo Nordisk A/S

Ethics review

Status: Approved
Approval date: 10/11/2015
Contact: