Growth Hormone Deficiency in ChildrenPhase 3REAL4NCT03811535
A Research Study in Children With a Low Level of Hormone to Grow. Treatment is Somapacitan Once a Week Compared to Norditropin® Once a Day (REAL4)
A Phase 3 study testing Somapacitan and Norditropin® in people with Growth Hormone Deficiency in Children, run by Novo Nordisk A/S at 139 sites in 26 countries.
Trial summary
The study compares 2 medicines for children who do not have enough hormone to grow: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Researchers will test to see how well somapacitan works. The study will also test if somapacitan is safe. Read more about this study
- Who is it for?
- Ages Up to 11 years
- Conditions the study is for
- Growth Hormone Deficiency in Children
- What is being tested?
- Somapacitan and Norditropin®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 139 sitesin 26 countries
- Study dates
- 20 May 2019to 30 Sep 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Prepubertal children: a) Boys: Age more than or equal to 2 years and 26 weeks and less than 11.0 years at screening. Testis volume less than 4 ml. b) Girls: Age more than or equal to 2 years and 26 weeks and less than 10.0 years at screening. Tanner stage 1 for breast development (no palpable glandular breast tissue)
- Confirmed diagnosis of growth hormone deficiency determined by two different growth hormone stimulation tests performed within 12 months prior to randomisation, defined as a peak growth hormone level of less than or equal to 10.0 ng/ml using the World Health Organisation (WHO) International Somatropin 98/574 standard
- Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and gender at screening according to the standards of Center for Disease Control and Prevention
- Impaired height velocity, defined as annualised height velocity below the 25th percentile for chronological age and gender according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening
- Insulin-like Growth Factor-I (IGF-I) less than -1.0 SDS at screening, compared to age and gender normalized range measured at central laboratory
- No prior exposure to growth hormone therapy or IGF-I treatment
Who cannot join
- Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements
- Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening
- Children requiring inhaled glucocorticoid therapy at a dose of greater than 400 μg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening
- Diagnosis of attention deficit hyperactivity disorder
- Concomitant administration of other treatments that may have an effect on growth, e.g. but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder
- Prior history or presence of malignancy including intracranial tumours
Trial locations and contacts
139 sites in 26 countries.
139 sites in 26 countries
United States27 sites
Van Meter Pediatric Endo PC
Atlanta, Georgia, 30318
Dell Children's Medical Center
Austin, Texas, 78723
Pediatric Endocrine & Wellness Center
Aventura, Florida, 33180
Univ of AL at Birmingham_BRM
Birmingham, Alabama, 35233
UBMD Peds-Div of Endo/Diabetes
Buffalo, New York, 14203
Rocky Mt Ped and Endo
Centennial, Colorado, 80112
CCHMC_Cinc
Cincinnati, Ohio, 45229
Cook Children's Medical Center
Fort Worth, Texas, 76104
Ped Endo Assoc PC-G.V
Greenwood Village, Colorado, 80111-2803
Riley Hospital For Children
Indianapolis, Indiana, 46202
University OF Iowa
Iowa City, Iowa, 52242
Children's Mercy Clinics
Kansas City, Missouri, 64111
The Docs
Las Vegas, Nevada, 89113
Children's Hospital Los Angeles - Endocrinology
Los Angeles, California, 90027
Valley Children's Hospital
Madera, California, 93636-8762
NYU Langone Hospital-LI
Mineola, New York, 11501
Univ of Minnesota M.C.H.
Minneapolis, Minnesota, 55454
Goryeb Children's Hospital
Morristown, New Jersey, 07962
Yale-New Haven Hospital
New Haven, Connecticut, 06504
Univ Oklahoma Sci Ctr OK City
Oklahoma City, Oklahoma, 73104
Children's Hosp Of Orange
Orange, California, 92868
UPMC Child Hosp-Pittsburgh
Pittsburgh, Pennsylvania, 15224
WakeMed Childn Endo-Dbt_Raleig
Raleigh, North Carolina, 27610
Sutter Valley Med Fdt Ped Endo
Sacramento, California, 95821
Children's Minnesota
Saint Paul, Minnesota, 55102
MultiCare Inst for Res & Innov
Tacoma, Washington, 98405
A.I. duPont Hospital for Children/Nemours
Wilmington, Delaware, 19803
Japan26 sites
Kurume University Hospital, Pediatrics
Fukuoka, 830-0011
Fukuoka Children's Hospital_Endocrinology and Metabolism
Fukuoka-shi, Fukuoka, 813-0017
National Hospital Organization FUKUYAMA MEDICAL CENTER_Pediatrics
Fukuyama-shi, Hiroshima, 720-8520
National Hospital Organization FUKUYAMA MEDICAL CENTER
Fukuyama-shi, Hiroshima, 720-8520
Fukuyama City Hospital_Department of Pediatrics
Fukuyama-shi, Hiroshima, 721-8511
Kanagawa Children's Medical Center_Endo and Metabo
Kanagawa, 232-8555
Hyogo Prefectual Kobe Children's Hospital_Metab & endo
Kobe-shi, Hyogo, 650-0047
Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
Kyoto, 602-8566
Ibaraki Children's Hospital_General Pediatrics
Mito, Ibaraki, 311-4145
Nara Prefecture General Medical Center_ Nara-shi, Nara
Nara-shi, Nara, 630-8581
Nara Prefecture General Medical Center_Pediatric
Nara-shi, Nara, 630-8581
Niigata University Medical & Dental Hospital_Pediatrics
Niigata-shi, Niigata, 951 8520
Aichi Children's Health and Medical Center
Obu-shi, Aichi, 474-8710
Okayama Medical Center_Cardiology
Okayama-shi, Okayama, 701-1192
Osaka City General Hospital, Pediatric Endocrinology and Me
Osaka, 534-0021
Osaka Women's and Children's Hospital
Osaka, 594-1101
Saitama Children's Medical Center, Endocrinorogy&Metabolism
Saitama-shi, Saitama, 330-8777
Hamamatsu University Hospital_Pediatrics
Shizuoka, 431-3192
Osaka University Hospital_Pediatrics
Suita-shi, Osaka, 565-0871
Institute of Science Tokyo Hospital_Pediatrics
Tokyo, 113-8519
KOUJIYA Kodomo Clinic
Tokyo, 144-0034
National Center for Child Health and Dev, Endo and Metabo
Tokyo, 157 8535
National Center for Child Health and Development_Endo and Metabo
Tokyo, 157 8535
Tanaka Growth Clinic
Tokyo, 158-0097
Keio University Hospital_Pediatrics
Tokyo, 160-8582
Tokyo Metropolitan Children's Medical Center_Endo and Metab
Tokyo, 183-8561
South Korea12 sites
Inje University Busan Paik Hospital
Busan, 47392
Kyungpook National University Hospital
Daegu, 41944
Seoul National University Bundang Hospital
Gyeonggi-do, 13620
Ajou University Hospital
Gyeonggi-do, 16499
Inha University Hospital
Incheon, 22332
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Kangdong Sacred Heart Hospital
Seoul, 05355
Asan Medical Center
Seoul, 05505
Samsung Medical Center_Seoul
Seoul, 06351
Ajou University Hospital
Suwon, Gyeonggi-do, 16499
France8 sites
Centre Hospitalier Universitaire D'Angers-2
Angers, 49100
Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
Bordeaux, 33000
Ap-Hp-Hopital de Bicetre
Le Kremlin-Bicêtre, 94270
Hopital de Bicetre_Le Kremlin-Bicetre
Le Kremlin-Bicêtre, 94275
Assistance Publique Hopitaux de Marseille-Hopital de La Timone-2
Marseille, 13005
Hopital de La Timone
Marseille Cédex 05, 13385
Ap-Hp-Hopital Necker
Paris, 75015
HOPITAL DES ENFANTS-HOPITAL PAULE DE VIGUIER - Pharmacie
Toulouse, 31059
Russia8 sites
Republic Children's Hospital of Ministry of Health of Udmurt
Izhevsk, 426009
Setchenov First Moscow State Medical University
Moscow, 119435
RMAPE
Moscow, 125373
Children's clinical city hospital #1
Novosibirsk, 630048
FSBEI of Higher Education "Rostov State Medical University"
Rostov-on-Don, 344013
SPSBHI City Children out-patient clinic #44
Saint Petersburg, 191144
Samara Regional Children Clinical Hospital n.a. N.N. Ivanova
Samara, 443079
Siberian State Medical University
Tomsk, 634050
United Kingdom7 sites
Addenbrooke's Hospital_Cambridge
Cambridge, CB2 0QQ
Hull Royal Infirmary
Hull, HU3 2JZ
Alder Hey Children's Hospital
Liverpool, L12 2AP
Royal London Hospital_London
London, E1 1BB
Royal Manchester Children's Hospital
Manchester, M13 9WL
St George's Hospital
Tooting, SW17 0RE
St Georges Hospital
Tooting, SW17 0RE
Serbia5 sites
University Children's Hospital Tirsova
Belgrade, 11000
Institute for Mother and Child Health Care of Serbia
Belgrade, 11070
University Clinical Centre Kragujevac
Kragujevac, 34000
University Clinical Centre Nis
Niš, RS, 18 000
Institute for Health Care of Children and Adolescents
Novi Sad, 21000
Austria4 sites
Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie
Graz, 8036
LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde
Salzburg, A 5020
LKH St. Poelten, Kinder-und Jugendheilkunde
Sankt Pölten, 3100
Salzkammergut-Klinikum Vöcklabruck
Vöcklabruck, 4840
Germany4 sites
Endokrinologikum Frankfurt
Frankfurt am Main, 60596
Auf der Bult Medizinisches Versorgungszentrum Hannover
Hanover, 30159
Uniklinik Tübingen - Kinder- und Jugendmedizin
Tübingen, 72076
Uniklinik Ulm - Dt. Zentrum für Kinder- und Jugendgesundheit (DZKJ)
Ulm, 89075
Israel4 sites
Rambam MC - Department of Pediatrics A
Haifa, 31096
Meir MC - Department of Paediatrics
Kfar Saba, 44281
Schneider MC - Endrocrinology and Diabetes
Petah Tikva, 49202
Shamir MC - Pediatric and Adolescents Endocrinology unit
Ẕerifin, 7033001
Italy4 sites
IRCCS Meyer Firenze
Florence, 50139
Ospedale Pediatrico Gaslini
Genova, 16147
Ospedale Maggiore Policlinico UO Endocrinologia Diabetolgia
Milan, 20122
Ospedale Pediatrico Bambino Gesu
Roma, 00165
Algeria3 sites
CHU Bab El Oued Pediatrics Dept
Algiers, 16000
Endo and Diab Dept El Oued
Algiers, 16000
endocrino-diabetology department, Hospital IBN BADIS.
Constantine, 25000
India3 sites
Amrita Institute Of Medical Sciences & Research Centre
Kochi, Kerala, 682041
All India Institute of Medical Sciences
New Dehli, New Delhi, 110029
Jehangir Clinical Development Centre
Pune, Maharashtra, 411001
Poland3 sites
Kliniczny Szpital Wojewodzki nr 2 im. Sw. Jadwigi Krolowej w Rzeszowie
Rzeszów, Podkarpackie Voivodeship, 35-301
SPSK nr 1 im Prof. T Sokolowskiego
Szczecin, 71-252
Instytut ''Pomnik - Centrum Zdrowia Dziecka''
Warsaw, 04-730
Switzerland3 sites
Universitäts-Kinderspital beider Basel
Basel, 4031
Med. Kinder- und Poliklinik
Bern, 3010
Kinderspital Endokrinologie, Zürich
Zurich, 8032
Ukraine3 sites
Kharkiv Regional Children's Clinical Hospital - Endocrinological department
Kharkiv, 61093
Komisarenko Institute of Endocrinology and Metabolism of NAMSU - Department of paediatric endocrine pathology
Kyiv, 04114
Vinnytsia Regional Clinical Endocrinological Centre - Therapeutic department #2
Vinnytsia, 21010
Canada2 sites
Stollery Children's Hospital
Edmonton, Alberta, T6G 2B7
Mntrl Chldrn Hsptl PedEndoMUHC
Montreal, Quebec, H4A 3J1
Estonia2 sites
Tallinn Children's Hospital
Tallinn, 13419
Tartu University Hospital Children's Clinic
Tartu, 50406
Hungary2 sites
Észak-Közép-budai Centrum, Szent János Kórház és Szakrendelő
Budapest, 1023
Szegedi Tudományegyetem Gyermekgyógyászati Klinika
Szeged, 6720
Spain2 sites
Hospital Sant Joan de Déu
Esplugues Llobregat(Barcelona), 08950
Hospital Clínico de Santiago de Compostela
Santiago de Compostela, A Coruña, 15706
Thailand2 sites
King Chulalongkorn Memorial hospital_Ped-Endocrinology
Bangkok, 10330
Phramongkutklao Hospital_Ped-Endo_Pediatrics
Bangkok, 10400
Denmark1 site
Rigshospitalet Klinik for Vækst og Reproduktion Afsnit 5064
Copenhagen Ø, 2100
About this study
Official title: A Trial Comparing the Effect and Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® in Children With Growth Hormone Deficiency
The study compares 2 medicines for children who do not have enough hormone to grow: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Researchers will test to see how well somapacitan works. The study will also test if somapacitan is safe. Participants will either get somapacitan or Norditropin® - which treatment participants get, is decided by chance. Both participants and the study doctor will know which treatment participants get. The study will last for 4 years. Participants will attend 19 clinic visits and have 1 phone call with the study doctor.
- Conditions
- Growth Hormone Deficiency in Children
- Being tested
- Somapacitan, Norditropin®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SomapacitanDrug
Somapacitan will be administered subcutaneously (s.c.; under the skin) once weekly by PDS290 pen-injector. Somapacitan can be injected any time during the once weekly dosing day. The dose will be calculated based on the subject's current body weight.
Norditropin®Drug
Norditropin® will be administered s.c. once daily by FlexPro® pen-injector. Norditropin® should be injected daily in the evening. The dose will be calculated based on the subject's current body weight.
| Study group | Role | What they receive |
|---|---|---|
| Somapacitan weekly | Experimental | Participants will receive somapacitan weekly for 52 weeks (main trial period). Participants completing the main trial period in both the treatment arms ('Somapacitan weekly' and 'Norditropin® daily') will receive somapacitan weekly for 3 years (extension trial period). Receives: Drug: Somapacitan |
| Norditropin® daily | Active comparator | Participants will receive Norditropin® daily for 52 weeks (main trial period). Receives: Drug: Norditropin® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Height Velocity: In-trial Observation Period
Height velocity (HV) was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: From baseline (week 0) to visit 7 (week 52)
Height Velocity: On-treatment Observation Period
Height velocity was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'on-treatment' observation period. On-treatment observation period: from first administration and up until last trial contact, visit 7 or 14 days after last administration, whichever comes first.
Measured: From baseline (week 0) to visit 7 (week 52)
Secondary outcomes (27)
Change in Bone Age
Change from baseline (week -2) in bone age at week 52 is presented. X-ray images of left hand and wrist for bone age assessment according to the Greulich and Pyle atlas were taken. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week -2), week 52
Change in Height Standard Deviation Score (HSDS)
Change from baseline (week 0) in HSDS at week 52 is presented. HSDS was derived using Centre for Disease Control and Prevention (CDC) standards. 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. Positive value in change from baseline in HSDS indicated that HSDS was better than baseline HSDS. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 52
Change in Height Velocity Standard Deviation Score (HV SDS)
Change from baseline (week 0) in HV SDS at week 52 is presented. HV SDS was calculated using the formula: HV SDS = (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 HV SDS 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. Positive value in change from baseline in HV SDS indicated that HV SDS was better than baseline HV SDS. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 52
Change in Fasting Plasma Glucose (FPG) at Week 52
Change from baseline (week -2) in FPG at week 52 is presented.
Measured: Baseline (week -2), week 52
Change in FPG at Week 104
Change from baseline (week -2) in FPG at week 104 is presented.
Measured: Baseline (week -2), week 104
Change in FPG at Week 156
Change from baseline (week -2) in FPG at week 156 is presented.
Measured: Baseline (week -2), week 156
Change in FPG at Week 208
Change from baseline (week -2) in FPG at week 208 is presented.
Measured: Baseline (week -2), week 208
Change in Homeostatic Model Assessment Steady State Beta Cell Function (HOMA-B) at Week 52
Change from baseline (week -2) in HOMA-B at week 52 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 * fasting insulin (picomoles per liter [pmol/L]) * 1/6(microunit per milliliter [µU/mL]))/ FPG(mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.
Measured: Baseline (week -2), week 52
Change in HOMA-B at Week 104
Change from baseline (week -2) in HOMA-B at week 104 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 * fasting insulin [pmol/L]) * 1/6 ([µU/mL] / FPG (mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.
Measured: Baseline (week -2), week 104
Change in HOMA-B at Week 156
Change from baseline (week -2) in HOMA-B at week 156 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 * fasting insulin [pmol/L]) * 1/6 ([µU/mL] / FPG (mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.
Measured: Baseline (week -2), week 156
Change in HOMA-B at Week 208
Change from baseline (week -2) in HOMA-B at week 208 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 * fasting insulin [pmol/L]) * 1/6 ([µU/mL] / FPG (mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.
Measured: Baseline (week -2), week 208
Change in Homeostatic Model Assessment Insulin Resistance (HOMA-IR) at Week 52
Change from baseline (week -2) in HOMA-IR at week 52 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) * 1/6(µU/mL) * FPG(mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.
Measured: Baseline (week -2), week 52
Change in HOMA-IR at Week 104
Change from baseline (week -2) in HOMA-IR at week 104 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) * 1/6(µU/mL) * FPG (mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.
Measured: Baseline (week -2), week 104
Change in HOMA-IR at Week 156
Change from baseline (week -2) in HOMA-IR at week 156 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) * 1/6(µU/mL) * FPG (mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.
Measured: Baseline (week -2), week 156
Change in HOMA-IR at Week 208
Change from baseline (week -2) in HOMA-IR at week 208 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) * 1/6(µU/mL) * FPG (mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.
Measured: Baseline (week -2), week 208
Change in Glycated Haemoglobin (HbA1c) at Week 52
Change from baseline (week -2) in HbA1c at week 52 is presented.
Measured: Baseline (week -2), week 52
Change in HbA1c at Week 104
Change from baseline (week -2) in HbA1c at week 104 is presented.
Measured: Baseline (week -2), week 104
Change in HbA1c at Week 156
Change from baseline (week -2) in HbA1c at week 156 is presented.
Measured: Baseline (week -2), week 156
Change in HbA1c at Week 208
Change from baseline (week -2) in HbA1c at week 208 is presented.
Measured: Baseline (week -2), week 208
Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) at Week 52
Change from baseline (week 0) in IGF-I SDS at week 52 is presented. 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. For participants with low IGF-I SDS at baseline, a positive change from baseline in IGF-I SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 52
Change in IGF-I SDS at Week 104
Change from baseline (week 0) in IGF-I SDS at week 104 is presented. 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. For participants with low IGF-I SDS at baseline, a positive change from baseline in IGF-I SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 104
Change in IGF-I SDS at Week 156
Change from baseline (week 0) in IGF-I SDS at week 156 is presented. 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. For participants with low IGF-I SDS at baseline, a positive change from baseline in IGF-I SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 156
Change in IGF-I SDS at Week 208
Change from baseline (week 0) in IGF-I SDS at week 208 is presented. 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. For participants with low IGF-I SDS at baseline, a positive change from baseline in IGF-I SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 208
Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Standard Deviation Score (SDS) at Week 52
Change from baseline (week 0) in IGFBP-3 SDS at week 52 is presented. 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. For participants with low IGFBP-3 SDS at baseline, a positive change from baseline in IGFBP-3 SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 52
Change in IGFBP-3 SDS at Week 104
Change from baseline (week 0) in IGFBP-3 SDS at week 104 is presented. 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. For participants with low IGFBP-3 SDS at baseline, a positive change from baseline in IGFBP-3 SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 104
Change in IGFBP-3 SDS at Week 156
Change from baseline (week 0) in IGFBP-3 SDS at week 156 is presented. 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. For participants with low IGFBP-3 SDS at baseline, a positive change from baseline in IGFBP-3 SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 156
Change in IGFBP-3 SDS at Week 208
Change from baseline (week 0) in IGFBP-3 SDS at week 208 is presented. 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. For participants with low IGFBP-3 SDS at baseline, a positive change from baseline in IGFBP-3 SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Measured: Baseline (week 0), week 208
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2019
- Study start20 May 2019
- Primary completion10 Nov 2021
- Study completion30 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Growth Hormone Deficiency in ChildrenStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will receive either somapacitan once weekly or Norditropin® once daily for 52 weeks (main trial period). All participants completing the main trial period will receive somapacitan weekly for 3 years (extension trial period).
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Transparency (dept. 2834), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03811535
- Sponsor's protocol ID
- NN8640-4263
- Other IDs
- U1111-1207-9691, 2018-000231-27, JapicCTI-194773, 2018
- Acronym
- REAL4
- Status last verified
- Sep 2026
- First submitted
- 18 Jan 2019
- Last updated
- 22 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
Miller BS, Blair JC, Rasmussen MH, Frystyk J, Lemminger AK, Maniatis A, Mori J, Bottcher V, Kim HS, Polak M, Horikawa R. Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4. Eur J Endocrinol. 2025 Apr 30;192(5):651-661. doi: 10.1093/ejendo/lvaf096.
PubMed 40400262Mori J, Ohata Y, Fujisawa Y, Sato Y, Rohrich S, Rasmussen MH, Bang RB, Horikawa R. Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial. Clin Endocrinol (Oxf). 2024 Apr;100(4):389-398. doi: 10.1111/cen.15025. Epub 2024 Feb 18.
PubMed 38368603Garner T, Clayton P, Hojby M, Murray P, Stevens A. Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency. J Clin Endocrinol Metab. 2024 Apr 19;109(5):1214-1221. doi: 10.1210/clinem/dgad717.
PubMed 38066644Miller BS, Blair JC, Rasmussen MH, Maniatis A, Mori J, Bottcher V, Kim HS, Bang RB, Polak M, Horikawa R. Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3090-3099. doi: 10.1210/clinem/dgad394.
PubMed 37406251Miller BS, Blair JC, Rasmussen MH, Maniatis A, Kildemoes RJ, Mori J, Polak M, Bang RB, Bottcher V, Stagi S, Horikawa R. Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial. J Clin Endocrinol Metab. 2022 Nov 25;107(12):3378-3388. doi: 10.1210/clinem/dgac513.
PubMed 36062966
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial Comparing the Effect and Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® in Children With Growth Hormone Deficiency
- ClinicalTrials.gov ID
- NCT03811535
- Acronym / sponsor ID
- REAL4 / NN8640-4263
- Conditions
- Growth Hormone Deficiency in Children
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 20 May 2019 (actual)
- Primary completion
- 10 Nov 2021 (actual)
- Study completion
- 30 Sep 2025 (actual)
- First posted
- 22 Jan 2019 (actual)
- Results
- Posted 4 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study compares 2 medicines for children who do not have enough hormone to grow: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Researchers will test to see how well somapacitan works. The study will also test if somapacitan is safe. Participants will either get somapacitan or Norditropin® - which treatment participants get, is decided by chance. Both participants and the study doctor will know which treatment participants get. The study will last for 4 years. Participants will attend 19 clinic visits and have 1 phone call with the study doctor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will receive either somapacitan once weekly or Norditropin® once daily for 52 weeks (main trial period). All participants completing the main trial period will receive somapacitan weekly for 3 years (extension trial period).
| Arm | Type | Receives |
|---|---|---|
| Somapacitan weekly | Experimental | Drug: SomapacitanParticipants will receive somapacitan weekly for 52 weeks (main trial period). Participants completing the main trial period in both the treatment arms ('Somapacitan weekly' and 'Norditropin® daily') will receive somapacitan weekly for 3 years (extension trial period). |
| Norditropin® daily | Active comparator | Drug: Norditropin®Participants will receive Norditropin® daily for 52 weeks (main trial period). |
Who may qualify
- Ages
- Up to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Prepubertal children: a) Boys: Age more than or equal to 2 years and 26 weeks and less than 11.0 years at screening. Testis volume less than 4 ml. b) Girls: Age more than or equal to 2 years and 26 weeks and less than 10.0 years at screening. Tanner stage 1 for breast development (no palpable glandular breast tissue)
- Confirmed diagnosis of growth hormone deficiency determined by two different growth hormone stimulation tests performed within 12 months prior to randomisation, defined as a peak growth hormone level of less than or equal to 10.0 ng/ml using the World Health Organisation (WHO) International Somatropin 98/574 standard
- Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and gender at screening according to the standards of Center for Disease Control and Prevention
- Impaired height velocity, defined as annualised height velocity below the 25th percentile for chronological age and gender according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening
- Insulin-like Growth Factor-I (IGF-I) less than -1.0 SDS at screening, compared to age and gender normalized range measured at central laboratory
Key exclusion criteria (6 listed)
- Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements
- Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening
- Children requiring inhaled glucocorticoid therapy at a dose of greater than 400 μg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening
- Diagnosis of attention deficit hyperactivity disorder
- Concomitant administration of other treatments that may have an effect on growth, e.g. but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SomapacitanSomapacitan will be administered subcutaneously (s.c.; under the skin) once weekly by PDS290 pen-injector. Somapacitan can be injected any time during the once weekly dosing day. The dose will be calculated based on the subject's current body weight. | Drug | Somapacitan weekly |
| Norditropin®Norditropin® will be administered s.c. once daily by FlexPro® pen-injector. Norditropin® should be injected daily in the evening. The dose will be calculated based on the subject's current body weight. | Drug | Norditropin® daily |
Primary outcome
Height Velocity: In-trial Observation Period
Time frame: From baseline (week 0) to visit 7 (week 52)
Height velocity (HV) was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.
Height Velocity: On-treatment Observation Period
Time frame: From baseline (week 0) to visit 7 (week 52)
Height velocity was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'on-treatment' observation period. On-treatment observation period: from first administration and up until last trial contact, visit 7 or 14 days after last administration, whichever comes first.
27 secondary outcomes
Change in Bone Age
Time frame: Baseline (week -2), week 52
Change in Height Standard Deviation Score (HSDS)
Time frame: Baseline (week 0), week 52
Change in Height Velocity Standard Deviation Score (HV SDS)
Time frame: Baseline (week 0), week 52
Change in Fasting Plasma Glucose (FPG) at Week 52
Time frame: Baseline (week -2), week 52
Change in FPG at Week 104
Time frame: Baseline (week -2), week 104
Change in FPG at Week 156
Time frame: Baseline (week -2), week 156
Change in FPG at Week 208
Time frame: Baseline (week -2), week 208
Change in Homeostatic Model Assessment Steady State Beta Cell Function (HOMA-B) at Week 52
Time frame: Baseline (week -2), week 52
Change in HOMA-B at Week 104
Time frame: Baseline (week -2), week 104
Change in HOMA-B at Week 156
Time frame: Baseline (week -2), week 156
Change in HOMA-B at Week 208
Time frame: Baseline (week -2), week 208
Change in Homeostatic Model Assessment Insulin Resistance (HOMA-IR) at Week 52
Time frame: Baseline (week -2), week 52
Change in HOMA-IR at Week 104
Time frame: Baseline (week -2), week 104
Change in HOMA-IR at Week 156
Time frame: Baseline (week -2), week 156
Change in HOMA-IR at Week 208
Time frame: Baseline (week -2), week 208
Change in Glycated Haemoglobin (HbA1c) at Week 52
Time frame: Baseline (week -2), week 52
Change in HbA1c at Week 104
Time frame: Baseline (week -2), week 104
Change in HbA1c at Week 156
Time frame: Baseline (week -2), week 156
Change in HbA1c at Week 208
Time frame: Baseline (week -2), week 208
Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) at Week 52
Time frame: Baseline (week 0), week 52
Change in IGF-I SDS at Week 104
Time frame: Baseline (week 0), week 104
Change in IGF-I SDS at Week 156
Time frame: Baseline (week 0), week 156
Change in IGF-I SDS at Week 208
Time frame: Baseline (week 0), week 208
Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Standard Deviation Score (SDS) at Week 52
Time frame: Baseline (week 0), week 52
Change in IGFBP-3 SDS at Week 104
Time frame: Baseline (week 0), week 104
Change in IGFBP-3 SDS at Week 156
Time frame: Baseline (week 0), week 156
Change in IGFBP-3 SDS at Week 208
Time frame: Baseline (week 0), week 208
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40400262Miller BS, Blair JC, Rasmussen MH, Frystyk J, Lemminger AK, Maniatis A, Mori J, Bottcher V, Kim HS, Polak M, Horikawa R. Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4. Eur J Endocrinol. 2025 Apr 30;192(5):651-661. doi: 10.1093/ejendo/lvaf096.
- Derived from this study: PubMed 38368603Mori J, Ohata Y, Fujisawa Y, Sato Y, Rohrich S, Rasmussen MH, Bang RB, Horikawa R. Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial. Clin Endocrinol (Oxf). 2024 Apr;100(4):389-398. doi: 10.1111/cen.15025. Epub 2024 Feb 18.
- Derived from this study: PubMed 38066644Garner T, Clayton P, Hojby M, Murray P, Stevens A. Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency. J Clin Endocrinol Metab. 2024 Apr 19;109(5):1214-1221. doi: 10.1210/clinem/dgad717.
- Derived from this study: PubMed 37406251Miller BS, Blair JC, Rasmussen MH, Maniatis A, Mori J, Bottcher V, Kim HS, Bang RB, Polak M, Horikawa R. Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3090-3099. doi: 10.1210/clinem/dgad394.
- Derived from this study: PubMed 36062966Miller BS, Blair JC, Rasmussen MH, Maniatis A, Kildemoes RJ, Mori J, Polak M, Bang RB, Bottcher V, Stagi S, Horikawa R. Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial. J Clin Endocrinol Metab. 2022 Nov 25;107(12):3378-3388. doi: 10.1210/clinem/dgac513.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Transparency (dept. 2834) study director
Novo Nordisk A/S
139 sites in 26 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Somapacitan and Norditropin® in people with Growth Hormone Deficiency in Children, run by Novo Nordisk A/S at 139 sites in 26 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 139 sites in United States, Japan, South Korea, France, Russia and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Height Velocity: In-trial Observation Period (time frame: From baseline (week 0) to visit 7 (week 52)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03811535, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.