Investigating Efficacy and Safety of Once-weekly NNC0195-0092 (Somapacitan) Treatment Compared to Daily Growth Hormone Treatment (Norditropin® FlexPro®) in Growth Hormone Treatment naïve Pre-pubertal Children With Growth Hormone Deficiency
- Conditions
- Growth Hormone DisorderGrowth Hormone Deficiency in Children
- Interventions
- Registration Number
- NCT02616562
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This trial is conducted globally. The aim of the trial is to investigate efficacy and safety of once-weekly NNC0195-0092 (somapacitan) treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in growth hormone treatment naïve pre-pubertal children with growth hormone deficiency.
The trial consists of a 26 week main trial period, followed by a 26 week extension trial period, a 104 week safety extension period, a 208 week longterm safety extension trial period and a 30 day follow up period. Participants receive NNC0195-0092 (somapacitan) (0.04 mg/kg/week) during the main trial and the extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the safety extension and the long-term safety extension periods. Two additional age groups, cohort II (age below 2 years and 26 weeks at screening) and cohort III (above 9 years (girls)/ above 10 years (boys) and equal to or below 17 years at screening) are included in the 208 week long-term safety extension trial period only.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
Cohort I:
- 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
Cohort II:
- Below 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-1 SDS below -1.0 at screening, compared to age and sex normalized range according to central laboratory measurements.
Cohort III:
Age:
-
Girls: Above 9.0 years and below or equal to 17.0 years at screening.
-
Boys: Above 10.0 years and below or equal to 17.0 years at screening.
-
Confirmed diagnosis of GHD
- 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 equal to or below 7.0 ng/ml. For children with three or more pituitary hormone deficiencies only one GH stimulation test is needed. FOR JAPAN ONLY: Confirmed diagnosis of GHD within 12 months prior to screening as determined by one GH stimulation tests for patients with intracranial organic disease or symptomatic hypoglycaemia and two different GH stimulation test for other patients, defined as a peak GH level of equal to or below 6 ng/ml by assay using recombinant GH standard.
- 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 below 14 years for females and bone age below 16 years for males.
- 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open labelled daily Norditropin® (0.034 mg/kg/day) somapacitan Participants receive Norditropin during the main trial, the extension period and the safety extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the long-term safety extension periods. Blinded NNC0195-0092 (somapacitan) (0.04 mg/kg/week) somapacitan Participants receive NNC0195-0092 (somapacitan) (0.04 mg/kg/week) during the main trial and the extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the safety extension and the long-term safety extension periods. Open labelled daily Norditropin® (0.034 mg/kg/day) Norditropin® FlexPro® pen Participants receive Norditropin during the main trial, the extension period and the safety extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the long-term safety extension periods. Blinded NNC0195-0092 (somapacitan) (0.08 mg/kg/week) somapacitan Participants receive NNC0195-0092 (somapacitan) (0.08 mg/kg/week) during the main trial and the extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the safety extension and the long-term safety extension periods. Blinded NNC0195-0092 (somapacitan) (0.16 mg/kg/week) somapacitan Participants receive the same dose (0.16 mg/kg/week) of NNC0195-0092 (somapacitan) during all 4 trial periods.
- Primary Outcome Measures
Name Time Method Cohort II and III: Incidence of adverse events, including injection site reactions, in children with GHD During 208 weeks Number of events
Cohort I: Height velocity (HV) during the first 26 weeks of treatment, measured as standing height with stadiometer Week 0-26 cm/year
- Secondary Outcome Measures
Name Time Method Insulin-like growth factor binding protein 3 (IGFBP-3) SDS Week 26-52 Typically -10 to +10
Height velocity Week 52 cm/year, derived from standing height from baseline (week 0) to week 52
Change in HV (height velocity) SDS Week 0-52 Baseline (week 0) HV SDS is derived from reported pre-trial standing height measured at minimum 6 months and maximum 18 months prior to screening visit to standing height at baseline (week 0)
Insulin-like growth factor 1 (IGF-I) SDS Week 26-52 Typically -10 to +10
Change in height standard deviation score (SDS) Week 26-52 Typically -10 to +10
Serum NNC0195-0092 (somapacitan) concentrations Week 52 ng/mL
Occurrence of anti-NNC0195-0092 (somapacitan) antibodies Week 364 Yes/no
Occurrence of anti-hGH antibodies Week 364 Yes/no
Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P) Week 52 The scores range from 0-100. A lower score indicates a better health state.
Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O) Week 52 The scores range from 0-100. A lower score indicates a better health state.
Incidence of adverse events, including injection site reactions Week 364 Number of events
Bone age Week 52 X-Ray of left hand and wrist, central assessed according to Greulich \& Pyle atlas progression vs. chronological age
Changes in emotional well-being score, physical health score, social well-being score and total score in Treatment Related Impact Measure - Child Growth Hormone Deficiency- Observer (TRIM-CGHD-O) Week 0-52 The scores range from 0-100. A lower score indicates a better health state.
Trial Locations
- Locations (37)
Landeskrankenhaus Villach
🇦🇹Villach, Austria
Hôpital Necker
🇫🇷Paris, France
Astrid Lindgrens Barnsjukhus
🇸🇪Stockholm, Sweden
Marmara University Medical Faculty
🇹🇷Istanbul, Turkey
Institute of Endocrinology and Metabolism of AMSU
🇺🇦Kyiv, Ukraine
HOPITAL SUD de RENNES
🇫🇷Rennes, France
Hôpital des Enfants
🇫🇷Toulouse cedex 9, France
Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
🇯🇵Kyoto, Japan
National Center for Child Health and Dev, Endo and Metabo
🇯🇵Tokyo, Japan
CCHMC_Cinc
🇺🇸Cincinnati, Ohio, United States
Deutsches Zentrum für Kinder- und Jugendgesundheit (DZKJ)
🇩🇪Ulm, Germany
Nemours/AI duPont Hosp-Chld
🇺🇸Wilmington, Delaware, United States
Clinique Médicale Pédiatrique
🇫🇷Nantes, France
Goryeb Children's Hospital
🇺🇸Morristown, New Jersey, United States
Rutgers-Rwjms
🇺🇸New Brunswick, New Jersey, United States
CPQuali Pesquisa Clínica Ltda
🇧🇷São Paulo, Sao Paulo, Brazil
NYU Langone Hospital-LI
🇺🇸Mineola, New York, United States
Kepler Universitätsklinikum GmbH - Med Campus IV (vorm.LFKK)
🇦🇹Linz, Upper Austria, Austria
Centre Hospitalier Régional Universitaire d' Angers
🇫🇷ANGERS cedex 09, France
CHU Pellegrin
🇫🇷Bordeaux, France
Amrita Institute Of Medical Sciences & Research Centre
🇮🇳Kochi, Kerala, India
Jehangir Clinical Development Centre
🇮🇳Pune, Maharashtra, India
All India Institute of Medical Sciences
🇮🇳New Dehli, New Delhi, India
Rambam Medical Center Children A Dept.
🇮🇱Haifa, Israel
Osaka City General Hospital, Pediatric Endocrinology and Me
🇯🇵Osaka, Japan
Tokyo Medical and Dental University Hospital
🇯🇵Tokyo, Japan
University Children's Hospital
🇸🇮Ljubljana, Slovenia
Ivano-Frankivsk Regional Clinical Children Hospital
🇺🇦Ivano-Frankivsk, Ukraine
Endokrinologikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Soroka Medical Center - Pediatric Endocrinology
🇮🇱Beer Sheva, Israel
Department of Pediatrics , Meir Medical Center
🇮🇱Kfar Saba, Israel
Endrocrinology & DM Schneider MC
🇮🇱Petah Tikva, Israel
St. Marianna University School of Medicine Hospital_Pediatrics
🇯🇵Kanagawa, Japan
Sheba Medical Center Pediatric Endocrinology
🇮🇱Tel Hashomer, Israel
Kurume University Hospital, Pediatrics
🇯🇵Fukuoka, Japan
Osaka Women's and Children's Hospital
🇯🇵Osaka, Japan
Institute of Science Tokyo Hospital
🇯🇵Tokyo, Japan