Clinical trial NCT02616562: 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Growth Hormone Disorder
Growth Hormone Deficiency in Children
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2015-11-30
Enrollment: 74
Sex: ALL
Minimum age (years): 30
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

  1. 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.
  2. 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Cohort I: Height velocity (HV) during the first 26 weeks of treatment, measured as standing height with stadiometer
timeFrame: Week 0-26
measure: Cohort II and III: Incidence of adverse events, including injection site reactions, in children with GHD
timeFrame: During 208 weeks
Secondary outcomes:
measure: Change in height standard deviation score (SDS)
timeFrame: Week 0-26
measure: Change in height standard deviation score (SDS)
timeFrame: Week 0-52
measure: Change in height standard deviation score (SDS)
timeFrame: Week 26-52
measure: Change in HV (height velocity) SDS
timeFrame: Week 0-26
measure: Change in HV (height velocity) SDS
timeFrame: Week 0-52
measure: Insulin-like growth factor 1 (IGF-I) SDS
timeFrame: Week 0-26
measure: Insulin-like growth factor 1 (IGF-I) SDS
timeFrame: Week 0-52
measure: Insulin-like growth factor 1 (IGF-I) SDS
timeFrame: Week 26-52
measure: Insulin-like growth factor binding protein 3 (IGFBP-3) SDS
timeFrame: Week 0-26
measure: Insulin-like growth factor binding protein 3 (IGFBP-3) SDS
timeFrame: Week 0-52
measure: Insulin-like growth factor binding protein 3 (IGFBP-3) SDS
timeFrame: Week 26-52
measure: Height velocity
timeFrame: Week 52
measure: Bone age
timeFrame: Week 52
measure: Serum NNC0195-0092 (somapacitan) concentrations
timeFrame: Week 52
measure: 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)
timeFrame: Week 0-26
measure: 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)
timeFrame: Week 0-52
measure: Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O)
timeFrame: Week 26
measure: Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O)
timeFrame: Week 52
measure: Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P)
timeFrame: Week 26
measure: Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P)
timeFrame: Week 52
measure: Incidence of adverse events, including injection site reactions
timeFrame: Week 364
measure: Occurrence of anti-NNC0195-0092 (somapacitan) antibodies
timeFrame: Week 364
measure: Occurrence of anti-hGH antibodies
timeFrame: Week 364
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Nemours/AI duPont Hosp-Chld
state: Delaware
city: Morristown
country: United States
facility: Goryeb Children's Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers-Rwjms
state: New Jersey
city: Mineola
country: United States
facility: NYU Langone Hospital-LI
state: New York
city: Cincinnati
country: United States
facility: CCHMC_Cinc
state: Ohio
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH - Med Campus IV (vorm.LFKK)
state: Upper Austria
city: Villach
country: Austria
facility: Landeskrankenhaus Villach
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica Ltda
state: Sao Paulo
city: ANGERS cedex 09
country: France
facility: Centre Hospitalier Régional Universitaire d' Angers
city: Bordeaux
country: France
facility: CHU Pellegrin
city: Nantes
country: France
facility: Clinique Médicale Pédiatrique
city: Paris
country: France
facility: Hôpital Necker
city: Rennes
country: France
facility: HOPITAL SUD de RENNES
city: Toulouse cedex 9
country: France
facility: Hôpital des Enfants
city: Frankfurt am Main
country: Germany
facility: Endokrinologikum Frankfurt
city: Ulm
country: Germany
facility: Deutsches Zentrum für Kinder- und Jugendgesundheit (DZKJ)
city: Kochi
country: India
facility: Amrita Institute Of Medical Sciences & Research Centre
state: Kerala
city: Pune
country: India
facility: Jehangir Clinical Development Centre
state: Maharashtra
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
state: New Delhi
city: Beer Sheva
country: Israel
facility: Soroka Medical Center - Pediatric Endocrinology
city: Haifa
country: Israel
facility: Rambam Medical Center Children A Dept.
city: Kfar Saba
country: Israel
facility: Department of Pediatrics , Meir Medical Center
city: Petah Tikva
country: Israel
facility: Endrocrinology & DM Schneider MC
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center Pediatric Endocrinology
city: Fukuoka
country: Japan
facility: Kurume University Hospital, Pediatrics
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital_Pediatrics
city: Kyoto
country: Japan
facility: Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
city: Osaka
country: Japan
facility: Osaka City General Hospital, Pediatric Endocrinology and Me
city: Osaka
country: Japan
facility: Osaka Women's and Children's Hospital
city: Tokyo
country: Japan
facility: Institute of Science Tokyo Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Tokyo
country: Japan
facility: National Center for Child Health and Dev, Endo and Metabo
city: Ljubljana
country: Slovenia
facility: University Children's Hospital
city: Stockholm
country: Sweden
facility: Astrid Lindgrens Barnsjukhus
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Children Hospital
city: Kyiv
country: Ukraine
facility: Institute of Endocrinology and Metabolism of AMSU
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
citation: Savendahl L, Battelino T, Hojby Rasmussen M, Brod M, Saenger P, Horikawa R. Effective GH Replacement With Once-weekly Somapacitan vs Daily GH in Children with GHD: 3-year Results From REAL 3. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1357-1367. doi: 10.1210/clinem/dgab928.
citation: Savendahl L, Battelino T, Brod M, Hojby Rasmussen M, Horikawa R, Juul RV, Saenger P; REAL 3 study group. Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1847-61. doi: 10.1210/clinem/dgz310.