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

Novo Nordisk A/S76 enrolled

Overview

This trial is conducted globally. The aim of the trial is to investigate 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. The main trial period will consist of 26 weeks of treatment, followed by a 26 week extension period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Growth Hormone Disorder Growth Hormone Deficiency in Children

Interventions

Eligibility

Sex: ALLMin age: 2 YearsMax age: 10 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Boys: Tanner stage 1 for pubic hair and testis volume below 4 ml , age at least 2 years and 26 weeks and below or equal to 10.0 years at screening * Girls: Tanner stage 1 for breast development (no palpable glandular breast tissue) and pubic hair, age at least 2 years and 26 weeks and below or equal to 9.0 years at screening * Confirmed diagnosis of GHD (growth hormone deficiency) within 12 months prior to screening as determined by two different GH (growth hormone) stimulation tests, defined as a peak GH level of below or equal to 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-for-age and weight-for-age percentiles CDC at screening * Annualized height velocity (HV) below the 25th percentile for CA (chronological age) and gender or below -0.7 SD (standard deviation) score for CA and sex, according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months Exclusion Criteria: * Any clinically significant abnormality likely to affect growth or the ability to evaluate * growth with standing 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 below-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

Locations (89)

Children's of Alabama

Birmingham, Alabama, United States

Children's Hospital Los Angeles - Endocrinology

Los Angeles, California, United States

Mattel Children's Hospital at UCLA

Los Angeles, California, United States

Valley Children's Hospital

Madera, California, United States

Novo Nordisk Clinical Trial Call Center

San Diego, California, United States

Outcomes

Primary Outcomes

Height Velocity (HV) (cm/Year) During the First 26 Weeks of Treatment, Measured as Standing Height With Stadiometer

Height velocity (HV) was derived from height measurements taken at baseline (week 0) and the week 26 as: HV = (height at 26 weeks visit- height at baseline) / (time from baseline to 26 weeks visit in years).

Time frame: Baseline (week 0), week 26

Cohort II and Cohort III - Adverse Events Rate, Including Injection Site Reactions in Children With GHD.

This primary outcome measure was analysed by cohort using descriptive statistics. Adverse event per 100 patient years are presented in this outcome measure.

Time frame: From week 156 up to week 364

Secondary Outcomes

Cohort I: Change in Height Standard Deviation Score (HSDS)

Change in height standard deviation score is presented from baseline (week 0) to end of the main trial period week 26 and end of extension trial period week 52. The formula to calculate HSDS is: HSDS = ((Height / M)\*\*L-1) / (L\*S). L: The gender and age-specific power in the Box-Cox transformation, M: The gender and age-specific median, S: The gender and age-specific generalized coefficient of variation. The range for HSDS was -10 to +10. Negative scores indicated a height below the mean height for a child with the same age and gender, whereas positive scores indicated a height above the mean height for a child with the same age and gender.

Time frame: Baseline (Week 0), week 26, week 52

Cohort I: Change in Height Velocity Standard Deviation Score (HVSDS)

Change in height velocity standard deviation score is presented from baseline (week 0) to end of main trial period week 26 and end of extension trial period week 52. HVSDS was calculated using the formula: HVSDS = (height velocity - mean)/standard deviation (SD), where height velocity was the height velocity variable measured, mean and SD of height velocity by gender and age for the reference population. The range for HVSDS was -10 to +10. Negative scores indicated a height velocity below the mean height velocity for a child with the same age and gender, whereas positive scores indicated a height velocity above the mean height velocity for a child with the same age and gender.

Time frame: Baseline (Week 0), week 26, week 52

Cohort I: Adverse Events Rate, Including Injection Site Reactions

Adverse events per 100 patient years are presented. AEs with an onset after the first administration of trial product and up until 14 days after last trial drug administration for withdrawn participants, and with an onset after the first administration of trial product and up until visit 32 (week 364) or 14 days after last trial drug administration, which ever comes first, for all other participants, are analysed.

Time frame: From week 0 Up to week 364

Cohort I: Occurrence of Anti-NNC0195-0092 and Anti-hGH Antibodies

Participants who developed anti-NNC0195-0092 and anti-hGH antibodies are reported in this outcome measure.

Time frame: From week 0 Up to week 364

Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS)

Change in IGF-I SDS is presented from baseline (week 0) to end of main trial period week 26 and end of extension period week 52. The range for IGF-I SDS was from -10 to +10. Negative scores indicated a IGF-I below the mean IGF-I for a child with the same age and gender, whereas positive scores indicated a IGF-I above the mean IGF-I for a child with the same age and gender.

Time frame: (Week 0), week 26, week 52

Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Standard Deviation Score (SDS)

Change in IGFBP-3 SDS is presented from baseline (week 0) to end of main trial period week 26 and end of extension trial period week 52. The range for IGFBP-3 SDS was from -10 to +10. Negative scores indicated a IGFBP-3 below the mean IGFBP-3 for a child with the same age and gender, whereas positive scores indicated a IGFBP-3 above the mean IGFBP-3 for a child with the same age and gender.

Time frame: Baseline (Week 0), week 26, week 52

Height Velocity (HV) (cm/Year) at Weeks 52 (Derived From Standing Height)

HV was derived from height measurements taken at baseline (week 0) and the week 52 as: HV = (height at 52 weeks visit-height at baseline) / (time from baseline to 52 weeks visit in years)

Time frame: Baseline (week 0); week 52

Bone Age Progression vs. Chronological Age Ratio

The bone age vs. chronological age ratio is presented at week 52. X-Ray of left hand and wrist, central assessed according to Greulich \& Pyle atlas were taken.

Time frame: At week 52

Serum Somapacitan Concentrations

Serum somapacitan concentrations are presented at week 52.

Time frame: At week 52

Changes in Emotional Well-being Score, Physical Health Score, Social Well-being Score and Total Score in TRIM-CGHD-O (Treatment Related Impact Measure - Child Growth Hormone Deficiency- Observer)

Change in Treatment Related Impact Measure from baseline (week 0) to week 26 and week 52 were assessed in children with growth hormone deficiency. This outcome measure was assessed using patient reported outcome (PRO) questionnaires with 3 domains, such as emotional well-being score, physical health score, social wellbeing core and total score. The total score was calculated by taking average of each domain. The scale range for each domain and total score was from 0-100 and a lower score indicates a better health state. TRIMCGHD-O was analysed using descriptive statistics.

Time frame: Baseline (Week 0), week 26, week 52

Total Score of TB-CGHD-O (The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer)

Total score of Treatment Burden Measure (observer) was assessed at week 26 and at week 52 in children with growth hormone deficiency. This outcome measure was assessed using PRO questionnaires. The scale range for total score was from 0-100 and a lower score indicates a better health state.

Time frame: At week 26, at week 52

Total Score of TB-CGHD-P (The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian)

Total score of Treatment Burden Measure (parent/guardian) is reported at week 26 and at week 52 in children with growth hormone deficiency. This outcome measure was assessed using PRO questionnaires. The scale range for total score was from 0-100 and a lower score indicates a better health state.

Time frame: At week 26, at week 52