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)

NCT03811535 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: NN8640-4263U1111-1207-96912018-000231-27JapicCTI-194773
• Study Type: interventional
• Target: 200
• Locations: 25 countries
• Sites: 133

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From baseline (week 0) to visit 7 (week 52)

Secondary Outcomes (27)

• Change in Bone Age

  Baseline (week -2), week 52

• Change in Height Standard Deviation Score (HSDS)

  Baseline (week 0), week 52

• Change in Height Velocity Standard Deviation Score (HV SDS)

  Baseline (week 0), week 52

• Change in Fasting Plasma Glucose (FPG) at Week 52

  Baseline (week -2), week 52

• Change in FPG at Week 104

  Baseline (week -2), week 104

Study Arms (2)

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).

Drug: Somapacitan

Norditropin® daily

ACTIVE COMPARATOR

Participants will receive Norditropin® daily for 52 weeks (main trial period).

Drug: Norditropin®

Interventions

Somapacitan DRUG

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.

Somapacitan weekly

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.

Norditropin® daily

Eligibility Criteria

• Age: Up to 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (135)

Univ of AL at Birmingham_BRM

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Los Angeles - Endocrinology

Los Angeles, California, 90027, United States

Location

Valley Children's Hospital

Madera, California, 93636-8762, United States

Location

Children's Hosp Of Orange

Orange, California, 92868, United States

Location

Sutter Valley Med Fdt Ped Endo

Sacramento, California, 95821, United States

Location

Rocky Mt Ped and Endo

Centennial, Colorado, 80112, United States

Location

Ped Endo Assoc PC-G.V

Greenwood Village, Colorado, 80111-2803, United States

Location

Yale-New Haven Hospital

New Haven, Connecticut, 06504, United States

Location

A.I. duPont Hospital for Children/Nemours

Wilmington, Delaware, 19803, United States

Location

Pediatric Endocrine & Wellness Center

Aventura, Florida, 33180, United States

Location

Van Meter Pediatric Endo PC

Atlanta, Georgia, 30318, United States

Location

Riley Hospital For Children

Indianapolis, Indiana, 46202, United States

Location

University OF Iowa

Iowa City, Iowa, 52242, United States

Location

Univ of Minnesota M.C.H.

Minneapolis, Minnesota, 55454, United States

Location

Children's Minnesota

Saint Paul, Minnesota, 55102, United States

Location

Children's Mercy Clinics

Kansas City, Missouri, 64111, United States

Location

The Docs

Las Vegas, Nevada, 89113, United States

Location

Goryeb Children's Hospital

Morristown, New Jersey, 07962, United States

Location

UBMD Peds-Div of Endo/Diabetes

Buffalo, New York, 14203, United States

Location

NYU Langone Hospital-LI

Mineola, New York, 11501, United States

Location

WakeMed Childn Endo-Dbt_Raleig

Raleigh, North Carolina, 27610, United States

Location

CCHMC_Cinc

Cincinnati, Ohio, 45229, United States

Location

Univ Oklahoma Sci Ctr OK City

Oklahoma City, Oklahoma, 73104, United States

Location

UPMC Child Hosp-Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Dell Children's Medical Center

Austin, Texas, 78723, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

MultiCare Inst for Res & Innov

Tacoma, Washington, 98405, United States

Location

CHU Bab El Oued Pediatrics Dept

Algiers, 16000, Algeria

Location

Endo and Diab Dept El Oued

Algiers, 16000, Algeria

Location

endocrino-diabetology department, Hospital IBN BADIS.

Constantine, 25000, Algeria

Location

Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie

Graz, 8036, Austria

Location

LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde

Salzburg, A 5020, Austria

Location

LKH St. Poelten, Kinder-und Jugendheilkunde

Sankt Pölten, 3100, Austria

Location

Salzkammergut-Klinikum Vöcklabruck

Vöcklabruck, 4840, Austria

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Mntrl Chldrn Hsptl PedEndoMUHC

Montreal, Quebec, H4A 3J1, Canada

Location

Rigshospitalet Klinik for Vækst og Reproduktion Afsnit 5064

Copenhagen Ø, 2100, Denmark

Location

Tallinn Children's Hospital

Tallinn, 13419, Estonia

Location

Tartu University Hospital Children's Clinic

Tartu, 50406, Estonia

Location

Centre Hospitalier Universitaire D'Angers-2

Angers, 49100, France

Location

Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin

Bordeaux, 33000, France

Location

Ap-Hp-Hopital de Bicetre-1

Le Kremlin-Bicêtre, 94270, France

Location

Hopital de Bicetre_Le Kremlin-Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

Assistance Publique Hopitaux de Marseille-Hopital de La Timone-2

Marseille, 13005, France

Location

Hopital de La Timone

Marseille Cédex 05, 13385, France

Location

Ap-Hp-Hopital Necker-2

Paris, 75015, France

Location

HOPITAL DES ENFANTS-HOPITAL PAULE DE VIGUIER - Pharmacie

Toulouse, 31059, France

Location

Endokrinologikum Frankfurt

Frankfurt am Main, 60596, Germany

Location

Auf der Bult Medizinisches Versorgungszentrum Hannover

Hanover, 30159, Germany

Location

Uniklinik Tübingen - Kinder- und Jugendmedizin

Tübingen, 72076, Germany

Location

Uniklinik Ulm - Dt. Zentrum für Kinder- und Jugendgesundheit (DZKJ)

Ulm, 89075, Germany

Location

Észak-Közép-budai Centrum, Szent János Kórház és Szakrendelő

Budapest, 1023, Hungary

Location

Szegedi Tudományegyetem Gyermekgyógyászati Klinika

Szeged, 6720, Hungary

Location

Amrita Institute Of Medical Sciences & Research Centre

Kochi, Kerala, 682041, India

Location

Jehangir Clinical Development Centre

Pune, Maharashtra, 411001, India

Location

All India Institute of Medical Sciences

New Dehli, New Delhi, 110029, India

Location

CHI Crumlin Dept of Endocrinology

Dublin, D12 N512, Ireland

Location

Rambam MC - Department of Pediatrics A

Haifa, 31096, Israel

Location

Meir MC - Department of Paediatrics

Kfar Saba, 44281, Israel

Location

Schneider MC - Endrocrinology and Diabetes

Petah Tikva, 49202, Israel

Location

Shamir MC - Pediatric and Adolescents Endocrinology unit

Ẕerifin, 7033001, Israel

Location

IRCCS Meyer Firenze

Florence, 50139, Italy

Location

Ospedale Pediatrico Gaslini

Genova, 16147, Italy

Location

Ospedale Maggiore Policlinico UO Endocrinologia Diabetolgia

Milan, 20122, Italy

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Kurume University Hospital, Pediatrics

Fukuoka, 830-0011, Japan

Location

Fukuoka Children's Hospital_Endocrinology and Metabolism

Fukuoka-shi, Fukuoka, 813-0017, Japan

Location

National Hospital Organization FUKUYAMA MEDICAL CENTER

Fukuyama-shi, Hiroshima, 720-8520, Japan

Location

Fukuyama City Hospital_Department of Pediatrics

Fukuyama-shi, Hiroshima, 721-8511, Japan

Location

Kanagawa Children's Medical Center, Dev. Endo and Metabo

Kanagawa, 232-8555, Japan

Location

Hyogo Prefectual Kobe Children's Hospital Dept. Metab & endo

Kobe-shi, Hyogo, 650-0047, Japan

Location

Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics

Kyoto, 602-8566, Japan

Location

Ibaraki Children's Hospital_General Pediatrics

Mito, Ibaraki, 311-4145, Japan

Location

Nara Prefecture General Medical Center_ Nara-shi, Nara

Nara-shi, Nara, 630-8581, Japan

Location

Niigata University Medical & Dental Hospital_Pediatrics

Niigata-shi, Niigata, 951 8520, Japan

Location

Aichi Children's Health and Medical Center

Obu-shi, Aichi, 474-8710, Japan

Location

Okayama Medical Center_Cardiology

Okayama-shi, Okayama, 701-1192, Japan

Location

Osaka City General Hospital, Pediatric Endocrinology and Me

Osaka, 534-0021, Japan

Location

Osaka Women's and Children's Hospital

Osaka, 594-1101, Japan

Location

Saitama Children's Medical Center, Endocrinorogy&Metabolism

Saitama-shi, Saitama, 330-8777, Japan

Location

Hamamatsu Univ. School of Medicine Hospital, Pediatrics

Shizuoka, 431-3192, Japan

Location

Osaka University Hospital_Pediatrics

Suita-shi, Osaka, 565-0871, Japan

Location

Institute of Science Tokyo Hospital_Pediatrics

Tokyo, 113-8519, Japan

Location

KOUJIYA Kodomo Clinic

Tokyo, 144-0034, Japan

Location

National Center for Child Health and Dev, Endo and Metabo

Tokyo, 157 8535, Japan

Location

Tanaka Growth Clinic

Tokyo, 158-0097, Japan

Location

Keio University Hospital, Pediatrics

Tokyo, 160-8582, Japan

Location

Tokyo Metropolitan Children's Medical Center_Endo and Metab

Tokyo, 183-8561, Japan

Location

Children's Clinical University Hospital

Riga, 1004, Latvia

Location

Haukeland Universitetssykehus, Barneklinikken

Bergen, 5021, Norway

Location

Kliniczny Szpital Wojewodzki nr 2 im. Sw. Jadwigi Krolowej w Rzeszowie

Rzeszów, Podkarpackie Voivodeship, 35-301, Poland

Location

SPSK nr 1 im Prof. T Sokolowskiego

Szczecin, 71-252, Poland

Location

Instytut ''Pomnik - Centrum Zdrowia Dziecka''

Warsaw, 04-730, Poland

Location

Republic Children's Hospital of Ministry of Health of Udmurt

Izhevsk, 426009, Russia

Location

Setchenov First Moscow State Medical University

Moscow, 119435, Russia

Location

RMAPE

Moscow, 125373, Russia

Location

Children's clinical city hospital #1

Novosibirsk, 630048, Russia

Location

FSBEI of Higher Education "Rostov State Medical University"

Rostov-on-Don, 344013, Russia

Location

SPSBHI City Children out-patient clinic #44

Saint Petersburg, 191144, Russia

Location

Samara Regional Children Clinical Hospital n.a. N.N. Ivanova

Samara, 443079, Russia

Location

Siberian State Medical University

Tomsk, 634050, Russia

Location

University Clinical Centre Nis

Niš, RS, 18 000, Serbia

Location

University Children's Hospital Tirsova

Belgrade, 11000, Serbia

Location

Institute for Mother and Child Health Care of Serbia

Belgrade, 11070, Serbia

Location

University Clinical Centre Kragujevac

Kragujevac, 34000, Serbia

Location

Institute for Health Care of Children and Adolescents

Novi Sad, 21000, Serbia

Location

University Children's Hospital

Ljubljana, 1525, Slovenia

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Inje University Busan Paik Hospital

Busan, 47392, South Korea

Location

Kyungpook National University Hospital

Daegu, 41944, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Ajou University Hospital

Gyeonggi-do, 16499, South Korea

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Kangdong Sacred Heart Hospital

Seoul, 05355, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center_Seoul

Seoul, 06351, South Korea

Location

Hospital Clínico de Santiago de Compostela

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Sant Joan de Déu

Esplugues Llobregat(Barcelona), 08950, Spain

Location

Universitäts-Kinderspital beider Basel

Basel, 4031, Switzerland

Location

Med. Kinder- und Poliklinik

Bern, 3010, Switzerland

Location

Kinderspital Endokrinologie, Zürich

Zurich, 8032, Switzerland

Location

King Chulalongkorn Memorial hospital_Ped-Endocrinology

Bangkok, 10330, Thailand

Location

Phramongkutklao Hospital_Ped-Endo_Pediatrics

Bangkok, 10400, Thailand

Location

Kharkiv Regional Children's Clinical Hospital - Endocrinological department

Kharkiv, 61093, Ukraine

Location

Komisarenko Institute of Endocrinology and Metabolism of NAMSU - Department of paediatric endocrine pathology

Kyiv, 04114, Ukraine

Location

Vinnytsia Regional Clinical Endocrinological Centre - Therapeutic department #2

Vinnytsia, 21010, Ukraine

Location

Addenbrooke's Hospital_Cambridge

Cambridge, CB2 0QQ, United Kingdom

Location

Hull Royal Infirmary

Hull, HU3 2JZ, United Kingdom

Location

Alder Hey Children's Hospital

Liverpool, L12 2AP, United Kingdom

Location

Royal London Hospital_London

London, E1 1BB, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

St George's Hospital

Tooting, SW17 0RE, United Kingdom

Location

St Georges Hospital

Tooting, SW17 0RE, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40400262 DERIVED

• Mori 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.

  PMID: 38368603 DERIVED

• Miller 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.

  PMID: 37406251 DERIVED

• Miller 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.

  PMID: 36062966 DERIVED

MeSH Terms

Interventions

somapacitan; Human Growth Hormone

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 22, 2019
• Study Start: May 20, 2019
• Primary Completion: November 10, 2021
• Study Completion: September 30, 2025
• Last Updated: January 6, 2026
• Results First Posted: August 4, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

TH (2); AU (4); US (27); DE (4); IE (1); NO (1); KR (11); CA (2); AL (3); CH (3); JP (23); RU (8); SE (5); HU (2); IT (4); IL (4); DK (1); ES (2); UA (3); FR (8); LA (1); GB (7); SL (1); PL (3); IN (3)