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

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

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 Overview

• Status: Completed
• Conditions: Growth Hormone Disorder; Growth Hormone Deficiency in Children
• Intervention / Treatment: Drug: somapacitan; Drug: Norditropin® FlexPro® pen

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
  • Graz, Austria, 8036
    • Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie
  • Salzburg, Austria, 5020
    • LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde
  • Sankt Pölten, Austria, 3100
    • LKH St. Poelten, Kinder-und Jugendheilkunde
  • Villach, Austria, 9500
    • Landeskrankenhaus Villach
  • Vöcklabruck, Austria, 4840
    • Salzkammergut-Klinikum Vöcklabruck
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Kepler Universitätsklinikum GmbH - Med Campus IV (vorm.LFKK)
• Belgium
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Brussels, Belgium, 1090
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc - Serv. Pédiatrie
  • Leuven, Belgium, 3000
    • UZ Leuven - Kindergeneeskunde
  • Liège, Belgium, 4030
    • CHU de Liège, site N.-D. des Bruyères
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80030-110
      • Serviço de Endocrinologia e Metabologia do HC-UFPR
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital São Lucas - PUC/RS
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01228-000
      • CPQuali Pesquisa Clinica Ltda
    • São Paulo, São Paulo, Brazil, 01228-000
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• France
  • Angers, France, 49033
    • Centre Hospitalier Universitaire D'Angers-2
  • Bordeaux, France, 33076
  • Bordeaux, France, 33076
    • Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
  • Nantes, France, 44000
    • Centre Hospitalier Universitaire de Nantes-Hopital Enfant-Adolescent
  • Paris, France, 75015
    • Ap-Hp-Hopital Necker
  • Rennes, France, 35056
    • HOPITAL SUD de RENNES
  • Toulouse, France, 31059
    • HOPITAL DES ENFANTS-HOPITAL PAULE DE VIGUIER - Pharmacie
• Germany
  • Frankfurt, Germany, 60596
  • Frankfurt am Main, Germany, 60596
    • Endokrinologikum Frankfurt
  • Ulm, Germany, 89075
    • Uniklinik Ulm - Dt. Zentrum für Kinder- und Jugendgesundheit (DZKJ)
• India
  • Kerala
    • Kochi, Kerala, India, 682041
      • Amrita Institute Of Medical Sciences & Research Centre
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • Jehangir Clinical Development Centre
  • New Delhi
    • New Dehli, New Delhi, India, 110029
      • All India Institute of Medical Sciences
    • New Dehli, New Delhi, India, 110029
• Israel
  • Beersheba, Israel, 84101
    • Soroka MC - Pediatric Endocrinology
  • Haifa, Israel, 31096
    • Rambam MC - Department of Pediatrics A
  • Kfar Saba, Israel, 44281
  • Kfar Saba, Israel, 44281
    • Meir MC - Department of Paediatrics
  • Petah Tikva, Israel, 49202
    • Schneider MC - Endrocrinology and Diabetes
  • Tel Litwinsky, Israel, 52621
    • Sheba MC - Pediatric endocrinology and adolescent diabetes clinics
• Japan
  • Fukuoka, Japan, 830-0011
    • Kurume University Hospital, Pediatrics
  • Fukuoka, Japan, 812-8582
    • Kyushu Univ. HP, Maternity & Perinatal Care Center
  • Kanagawa, Japan, 216-8511
    • St. Marianna University School of Medicine Hospital_Pediatrics
  • Kyoto, Japan, 602-8566
    • Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital, Pediatric Endocrinology and Me
  • Osaka, Japan, 594-1101
    • Osaka Women's and Children's Hospital
  • Osaka, Japan, 553-0003
    • JCHO Osaka Hospital_Pediatric
  • Tokyo, Japan, 113-8519
    • Tokyo Medical and Dental University Hospital
  • Tokyo, Japan, 157 8535
    • National Center for Child Health and Dev, Endo and Metabo
  • Tokyo, Japan, 157 8535
  • Tokyo, Japan, 113-8519
    • Institute of Science Tokyo Hospital_Pediatrics
• Slovenia
  • Ljubljana, Slovenia, 1525
  • Ljubljana, Slovenia, 1525
    • University Children's Hospital
• Sweden
  • Stockholm, Sweden, 171 76
  • Stockholm, Sweden, 171 76
    • Astrid Lindgrens Barnsjukhus
  • Umeå, Sweden, 901 85
    • Barn och ungdomscentrum Västerbotten
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Üniversitesi Hastanesi- Endokrinoloji
  • Istanbul, Turkey (Türkiye), 34093
  • Istanbul, Turkey (Türkiye), 34093
    • I.U Istanbul Medical Faculty
  • Istanbul, Turkey (Türkiye), 34854
    • Marmara University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34854
    • Marmara Üniversitesi Pendik EAH- Başıbüyük Yerleşkesi- Kardiyoloji
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Regional Clinical Children Hospital - Endocrinology dept.
  • Kiev, Ukraine, 04114
  • Kyiv, Ukraine, 04114
    • Komisarenko Institute of Endocrinology and Metabolism of NAMSU - Department of paediatric endocrine pathology
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • California
    • Los Angeles, California, United States, 90095
      • Mattel Children's Hospital at UCLA
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles - Endocrinology
    • Madera, California, United States, 93636-8762
      • Valley Children's Hospital
    • San Diego, California, United States, 92123
      • Novo Nordisk Clinical Trial Call Center
    • San Diego, California, United States, 92123
      • The Regents of the Univ of CA
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Rocky Mt Ped and Endo
    • Greenwood Village, Colorado, United States, 80111-2803
      • Ped Endo Assoc PC-G.V
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/AI duPont Hosp-Chld
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • The Endocrine Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Childrens Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • Novo Nordisk Clinical Trial Call Center
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota_Minneapolis_2
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Goryeb Children's Hospital
    • Morristown, New Jersey, United States, 07962
      • Novo Nordisk Clinical Trial Call Center
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-RWJMS
  • New York
    • Buffalo, New York, United States, 14203
      • UBMD Peds-Div of Endo/Diabetes
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital-LI
    • Mineola, New York, United States, 11501
      • Novo Nordisk Clinical Trial Call Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • CCHMC_Cinc
    • Cincinnati, Ohio, United States, 45229
      • Novo Nordisk Clinical Trial Call Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • University Of Oklahoma-Tulsa
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Pediatric Research Institute
    • Plano, Texas, United States, 75093
      • Endocrine Associates Of Dallas
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hsptl Of The Kings
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Inst for Res & Innov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort I Norditropin/somapacitan; Participants received Norditropin subcutaneously daily in main trial period, extension trial period and safety extension trial period. After completing the safety extension trial period (week 156), participants who received Norditropin were allocated to open-labelled Somapacitan dose 3 subcutaneously once weekly for the 208-week (up till week 364) long-term safety extension period. After week 364, participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.	Drug: somapacitan; Administered subcutaneously (s.c., under the skin) once-weekly.; Other Names: NNC0195-0092; Drug: Norditropin® FlexPro® pen; Administered subcutaneously (s.c., under the skin) once daily.
Experimental: Cohort I somapacitan pooled; Participants were randomized (1:1:1) to receive Somapacitan treatment (dose 1/dose 2/dose 3) subcutaneously once-weekly during the 26-week main trial period and the 26-week extension trial period. After completing the main and extension trial periods (week 52), all participants initially randomized to double-blinded Somapacitan received open-labelled Somapacitan dose 3 for the 104-week safety extension trial period. After completing the safety extension trial period (week 156), all participants in cohort I were allocated to open-labelled somapacitan dose 3 for the 208-week (up till week 364) long-term safety extension period. In extension after week 364 period participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.	Drug: somapacitan; Administered subcutaneously (s.c., under the skin) once-weekly.; Other Names: NNC0195-0092
Experimental: Cohort II somapacitan previously treated; Participant who was previously treated with GH (Growth hormone) prior to enrollment in the trial at week 156, received somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.	Drug: somapacitan; Administered subcutaneously (s.c., under the skin) once-weekly.; Other Names: NNC0195-0092
Experimental: Cohort III somapacitan treatment naive; Participants who were naive to treatment with GH prior to enrolment in the trial at week 156, received open-labelled somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.	Drug: somapacitan; Administered subcutaneously (s.c., under the skin) once-weekly.; Other Names: NNC0195-0092
Experimental: Cohort III somapacitan previously treated; Participants who were previously treated with GH prior to enrollment in the trial at week 156, received open-labelled somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.	Drug: somapacitan; Administered subcutaneously (s.c., under the skin) once-weekly.; Other Names: NNC0195-0092

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	From week 156 up to week 364

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	(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.	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)	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.	At week 52
Serum Somapacitan Concentrations	Serum somapacitan concentrations are presented at week 52.	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.	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.	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.	At week 26, at week 52

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• 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.
• 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.
• Savendahl L, Battelino T, Hojby Rasmussen M, Brod M, Rohrich S, Saenger P, Horikawa R. Weekly Somapacitan in GH Deficiency: 4-Year Efficacy, Safety, and Treatment/Disease Burden Results From REAL 3. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2569-2578. doi: 10.1210/clinem/dgad183.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2016
• Primary Completion (Actual): September 26, 2024
• Study Completion (Actual): September 26, 2024

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimated): November 30, 2015

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Bone Diseases, Endocrine; Bone Diseases, Developmental; Dwarfism; Hypopituitarism; Endocrine System Diseases; Dwarfism, Pituitary; somapacitan; NNC0195-0092
• Other Study ID Numbers: NN8640-4172; 2015-000531-32 (EudraCT Number); U1111-1166-7062 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No