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

Growth Hormone Disorder Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02616562
• Other study ID #: NN8640-4172
• Secondary ID: 2015-000531-32U1
• Status: Recruiting
• Phase: Phase 2
• Start date: March 23, 2016
• Est. completion date: September 27, 2024

Study information

• Verified date: June 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: September 27, 2024
• Est. primary completion date: August 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Months to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency in Children
• Growth Hormone Disorder

Intervention

Drug:
• somapacitan
Administered subcutaneously (s.c., under the skin) once-weekly.
• Norditropin® FlexPro® pen
Administered subcutaneously (s.c., under the skin) once daily.

Locations

Country	Name	City	State
Austria	Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie	Graz
Austria	Kepler Universitätsklinikum GmbH - Med Campus IV (vorm.LFKK)	Linz	Upper Austria
Austria	LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde	Salzburg
Austria	LKH St. Poelten, Kinder-und Jugendheilkunde	St. Poelten
Austria	Landeskrankenhaus Villach	Villach
Austria	Salzkammergut-Klinikum Vöcklabruck	Vöcklabruck
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires Saint-Luc - Serv. Pédiatrie	Bruxelles
Belgium	UZ Leuven - Kindergeneeskunde	Leuven
Belgium	CHU de Liège, site N.-D. des Bruyères	Liège
Brazil	Serviço de Endocrinologia e Metabologia do HC-UFPR	Curitiba	Paraná
Brazil	Hospital São Lucas - PUC/RS	Porto Alegre	Rio Grande Do Sul
Brazil	CPQuali Pesquisa Clínica Ltda	São Paulo	Sao Paulo
France	Centre Hospitalier Régional Universitaire d' Angers	ANGERS cedex 09
France	CHU Pellegrin	Bordeaux
France	Clinique Médicale Pédiatrique	Nantes
France	Hôpital Necker	Paris
France	HOPITAL SUD de RENNES	Rennes
France	Hôpital des Enfants	Toulouse cedex 9
Germany	Endokrinologikum Frankfurt	Frankfurt am Main
Germany	Universitätsklinikum Ulm für Kinder- und Jugendmedizin	Ulm
India	Amrita Institute Of Medical Sciences & Research Centre	Kochi	Kerala
India	All India Institute of Medical Sciences	New Dehli	New Delhi
India	Jehangir Clinical Development Centre	Pune	Maharashtra
Israel	Soroka Medical Center - Pediatric Endocrinology	Beer Sheva
Israel	Rambam Medical Center Children A Dept.	Haifa
Israel	Department of Pediatrics , Meir Medical Center	Kfar Saba
Israel	Endrocrinology & DM Schneider MC	Petah Tikva
Israel	Sheba Medical Center Pediatric Endocrinology	Tel Hashomer
Japan	Kurume University Hospital, Pediatrics	Fukuoka
Japan	Kyushu Univ. HP, Maternity & Perinatal Care Center	Fukuoka
Japan	St. Marianna University School of Medicine Hospital_Pediatrics	Kanagawa
Japan	St. Marianna University School of Medicine Hospital_Pediatrics	Kanagawa
Japan	Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics	Kyoto
Japan	JCHO Osaka HP, Pediatric	Osaka
Japan	Osaka City General Hospital, Pediatric Endocrinology and Me	Osaka
Japan	Osaka Women's and Children's Hospital	Osaka
Japan	National Center for Child Health and Dev, Endo and Metabo	Tokyo
Japan	Tokyo Medical and Dental University Hospital	Tokyo
Japan	Tokyo Medical and Dental University Hospital	Tokyo
Slovenia	PeK - Dept. of Paediatric Endocrinology, Diabetes and Metabolism	Ljubljana
Sweden	Astrid Lindgrens Barnsjukhus	Stockholm
Sweden	Barn och ungdomskliniken Västerbotten	Umeå
Turkey	Cukurova Universitesi Tip Fakultesi_Istanbul	Adana
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	I.U Istanbul Medical Faculty	Istanbul
Turkey	Marmara University Medical Faculty	Istanbul
Ukraine	Ivano-Frankivsk Regional Clinical Children Hospital	Ivano-Frankivsk
Ukraine	Institute of Endocrinology and Metabolism of AMSU	Kyiv
United States	Rocky Mt Ped and Endo	Centennial	Colorado
United States	CCHMC_Cinc	Cincinnati	Ohio
United States	NYU Langone Hospital-LI	Mineola	New York
United States	University of Minnesota_Minneapolis_2	Minneapolis	Minnesota
United States	Goryeb Children's Hospital	Morristown	New Jersey
United States	Rutgers-Rwjms	New Brunswick	New Jersey
United States	The Regents of the Univ of CA	San Diego	California
United States	MultiCare Inst for Res & Innov	Tacoma	Washington
United States	Nemours/AI duPont Hosp-Chld	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort I: Height velocity (HV) during the first 26 weeks of treatment, measured as standing height with stadiometer	cm/year	Week 0-26
Primary	Cohort II and III: Incidence of adverse events, including injection site reactions, in children with GHD	Number of events	During 208 weeks
Secondary	Change in height standard deviation score (SDS)	Typically -10 to +10	Week 0-26
Secondary	Change in height standard deviation score (SDS)	Typically -10 to +10	Week 0-52
Secondary	Change in height standard deviation score (SDS)	Typically -10 to +10	Week 26-52
Secondary	Change in HV (height velocity) SDS	Typically -10 to +10. 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)	Week 0-26
Secondary	Change in HV (height velocity) SDS	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)	Week 0-52
Secondary	Insulin-like growth factor 1 (IGF-I) SDS	Typically -10 to +10	Week 0-26
Secondary	Insulin-like growth factor 1 (IGF-I) SDS	Typically -10 to +10	Week 0-52
Secondary	Insulin-like growth factor 1 (IGF-I) SDS	Typically -10 to +10	Week 26-52
Secondary	Insulin-like growth factor binding protein 3 (IGFBP-3) SDS	Typically -10 to +10	Week 0-26
Secondary	Insulin-like growth factor binding protein 3 (IGFBP-3) SDS	Typically -10 to +10	Week 0-52
Secondary	Insulin-like growth factor binding protein 3 (IGFBP-3) SDS	Typically -10 to +10	Week 26-52
Secondary	Height velocity	cm/year, derived from standing height from baseline (week 0) to week 52	Week 52
Secondary	Bone age	X-Ray of left hand and wrist, central assessed according to Greulich & Pyle atlas progression vs. chronological age	Week 52
Secondary	Serum NNC0195-0092 (somapacitan) concentrations	ng/mL	Week 52
Secondary	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)	The scores range from 0-100. A lower score indicates a better health state.	Week 0-26
Secondary	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)	The scores range from 0-100. A lower score indicates a better health state.	Week 0-52
Secondary	Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O)	The scores range from 0-100. A lower score indicates a better health state.	Week 26
Secondary	Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O)	The scores range from 0-100. A lower score indicates a better health state.	Week 52
Secondary	Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P)	The scores range from 0-100. A lower score indicates a better health state.	Week 26
Secondary	Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P)	The scores range from 0-100. A lower score indicates a better health state.	Week 52
Secondary	Incidence of adverse events, including injection site reactions	Number of events	Week 364
Secondary	Occurrence of anti-NNC0195-0092 (somapacitan) antibodies	Yes/no	Week 364
Secondary	Occurrence of anti-hGH antibodies	Yes/no	Week 364