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)

NCT ID: NCT03811535

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2025-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Norditropin® daily

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

Group Type: ACTIVE_COMPARATOR

Norditropin®

Intervention Type: 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.

Somapacitan weekly

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).

Group Type: EXPERIMENTAL

Somapacitan

Intervention Type: 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.

Interventions

Somapacitan

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Transparency (dept. 2834)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Univ of AL at Birmingham_BRM

Birmingham, Alabama, United States

Children's Hospital Los Angeles - Endocrinology

Los Angeles, California, United States

Valley Children's Hospital

Madera, California, United States

Children's Hosp Of Orange

Orange, California, United States

Sutter Valley Med Fdt Ped Endo

Sacramento, California, United States

Rocky Mt Ped and Endo

Centennial, Colorado, United States

Ped Endo Assoc PC-G.V

Greenwood Village, Colorado, United States

Yale-New Haven Hospital

New Haven, Connecticut, United States

A.I. duPont Hospital for Children/Nemours

Wilmington, Delaware, United States

Pediatric Endocrine & Wellness Center

Aventura, Florida, United States

Van Meter Pediatric Endo PC

Atlanta, Georgia, United States

Riley Hospital For Children

Indianapolis, Indiana, United States

University OF Iowa

Iowa City, Iowa, United States

Univ of Minnesota M.C.H.

Minneapolis, Minnesota, United States

Children's Minnesota

Saint Paul, Minnesota, United States

Children's Mercy Clinics

Kansas City, Missouri, United States

The Docs

Las Vegas, Nevada, United States

Goryeb Children's Hospital

Morristown, New Jersey, United States

UBMD Peds-Div of Endo/Diabetes

Buffalo, New York, United States

NYU Langone Hospital-LI

Mineola, New York, United States

WakeMed Childn Endo-Dbt_Raleig

Raleigh, North Carolina, United States

CCHMC_Cinc

Cincinnati, Ohio, United States

Univ Oklahoma Sci Ctr OK City

Oklahoma City, Oklahoma, United States

UPMC Child Hosp-Pittsburgh

Pittsburgh, Pennsylvania, United States

Dell Children's Medical Center

Austin, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

MultiCare Inst for Res & Innov

Tacoma, Washington, United States

CHU Bab El Oued Pediatrics Dept

Algiers, , Algeria

Endo and Diab Dept El Oued

Algiers, , Algeria

endocrino-diabetology department, Hospital IBN BADIS.

Constantine, , Algeria

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

Graz, , Austria

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

Salzburg, , Austria

LKH St. Poelten, Kinder-und Jugendheilkunde

Sankt Pölten, , Austria

Salzkammergut-Klinikum Vöcklabruck

Vöcklabruck, , Austria

Stollery Children's Hospital

Edmonton, Alberta, Canada

Mntrl Chldrn Hsptl PedEndoMUHC

Montreal, Quebec, Canada

Rigshospitalet Klinik for Vækst og Reproduktion Afsnit 5064

Copenhagen Ø, , Denmark

Tallinn Children's Hospital

Tallinn, , Estonia

Tartu University Hospital Children's Clinic

Tartu, , Estonia

Centre Hospitalier Universitaire D'Angers-2

Angers, , France

Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin

Bordeaux, , France

Ap-Hp-Hopital de Bicetre-1

Le Kremlin-Bicêtre, , France

Hopital de Bicetre_Le Kremlin-Bicetre

Le Kremlin-Bicêtre, , France

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

Marseille, , France

Hopital de La Timone

Marseille Cédex 05, , France

Ap-Hp-Hopital Necker-2

Paris, , France

HOPITAL DES ENFANTS-HOPITAL PAULE DE VIGUIER - Pharmacie

Toulouse, , France

Endokrinologikum Frankfurt

Frankfurt am Main, , Germany

Auf der Bult Medizinisches Versorgungszentrum Hannover

Hanover, , Germany

Uniklinik Tübingen - Kinder- und Jugendmedizin

Tübingen, , Germany

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

Ulm, , Germany

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

Budapest, , Hungary

Szegedi Tudományegyetem Gyermekgyógyászati Klinika

Szeged, , Hungary

Amrita Institute Of Medical Sciences & Research Centre

Kochi, Kerala, India

Jehangir Clinical Development Centre

Pune, Maharashtra, India

All India Institute of Medical Sciences

New Dehli, New Delhi, India

CHI Crumlin Dept of Endocrinology

Dublin, , Ireland

Rambam MC - Department of Pediatrics A

Haifa, , Israel

Meir MC - Department of Paediatrics

Kfar Saba, , Israel

Schneider MC - Endrocrinology and Diabetes

Petah Tikva, , Israel

Shamir MC - Pediatric and Adolescents Endocrinology unit

Ẕerifin, , Israel

IRCCS Meyer Firenze

Florence, , Italy

Ospedale Pediatrico Gaslini

Genova, , Italy

Ospedale Maggiore Policlinico UO Endocrinologia Diabetolgia

Milan, , Italy

Ospedale Pediatrico Bambino Gesu

Roma, , Italy

Kurume University Hospital, Pediatrics

Fukuoka, , Japan

Fukuoka Children's Hospital_Endocrinology and Metabolism

Fukuoka-shi, Fukuoka, , Japan

National Hospital Organization FUKUYAMA MEDICAL CENTER

Fukuyama-shi, Hiroshima, , Japan

Fukuyama City Hospital_Department of Pediatrics

Fukuyama-shi, Hiroshima, , Japan

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

Kanagawa, , Japan

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

Kobe-shi, Hyogo, , Japan

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

Kyoto, , Japan

Ibaraki Children's Hospital_General Pediatrics

Mito, Ibaraki, , Japan

Nara Prefecture General Medical Center_ Nara-shi, Nara

Nara-shi, Nara, , Japan

Niigata University Medical & Dental Hospital_Pediatrics

Niigata-shi, Niigata, , Japan

Aichi Children's Health and Medical Center

Obu-shi, Aichi, , Japan

Okayama Medical Center_Cardiology

Okayama-shi, Okayama, , Japan

Osaka City General Hospital, Pediatric Endocrinology and Me

Osaka, , Japan

Osaka Women's and Children's Hospital

Osaka, , Japan

Saitama Children's Medical Center, Endocrinorogy&Metabolism

Saitama-shi, Saitama, , Japan

Hamamatsu Univ. School of Medicine Hospital, Pediatrics

Shizuoka, , Japan

Osaka University Hospital_Pediatrics

Suita-shi, Osaka, , Japan

Institute of Science Tokyo Hospital_Pediatrics

Tokyo, , Japan

KOUJIYA Kodomo Clinic

Tokyo, , Japan

National Center for Child Health and Dev, Endo and Metabo

Tokyo, , Japan

Tanaka Growth Clinic

Tokyo, , Japan

Keio University Hospital, Pediatrics

Tokyo, , Japan

Tokyo Metropolitan Children's Medical Center_Endo and Metab

Tokyo, , Japan

Children's Clinical University Hospital

Riga, , Latvia

Haukeland Universitetssykehus, Barneklinikken

Bergen, , Norway

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

Rzeszów, Podkarpackie Voivodeship, Poland

SPSK nr 1 im Prof. T Sokolowskiego

Szczecin, , Poland

Instytut ''Pomnik - Centrum Zdrowia Dziecka''

Warsaw, , Poland

Republic Children's Hospital of Ministry of Health of Udmurt

Izhevsk, , Russia

Setchenov First Moscow State Medical University

Moscow, , Russia

RMAPE

Moscow, , Russia

Children's clinical city hospital #1

Novosibirsk, , Russia

FSBEI of Higher Education "Rostov State Medical University"

Rostov-on-Don, , Russia

SPSBHI City Children out-patient clinic #44

Saint Petersburg, , Russia

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

Samara, , Russia

Siberian State Medical University

Tomsk, , Russia

University Clinical Centre Nis

Niš, RS, Serbia

University Children's Hospital Tirsova

Belgrade, , Serbia

Institute for Mother and Child Health Care of Serbia

Belgrade, , Serbia

University Clinical Centre Kragujevac

Kragujevac, , Serbia

Institute for Health Care of Children and Adolescents

Novi Sad, , Serbia

University Children's Hospital

Ljubljana, , Slovenia

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Inje University Busan Paik Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Ajou University Hospital

Gyeonggi-do, , South Korea

Inha University Hospital

Incheon, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Kangdong Sacred Heart Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center_Seoul

Seoul, , South Korea

Hospital Clínico de Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Hospital Sant Joan de Déu

Esplugues Llobregat(Barcelona), , Spain

Universitäts-Kinderspital beider Basel

Basel, , Switzerland

Med. Kinder- und Poliklinik

Bern, , Switzerland

Kinderspital Endokrinologie, Zürich

Zurich, , Switzerland

King Chulalongkorn Memorial hospital_Ped-Endocrinology

Bangkok, , Thailand

Phramongkutklao Hospital_Ped-Endo_Pediatrics

Bangkok, , Thailand

Kharkiv Regional Children's Clinical Hospital - Endocrinological department

Kharkiv, , Ukraine

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

Kyiv, , Ukraine

Vinnytsia Regional Clinical Endocrinological Centre - Therapeutic department #2

Vinnytsia, , Ukraine

Addenbrooke's Hospital_Cambridge

Cambridge, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

Alder Hey Children's Hospital

Liverpool, , United Kingdom

Royal London Hospital_London

London, , United Kingdom

Royal Manchester Children's Hospital

Manchester, , United Kingdom

St George's Hospital

Tooting, , United Kingdom

St Georges Hospital

Tooting, , United Kingdom

Countries

United States; Algeria; Austria; Canada; Denmark; Estonia; France; Germany; Hungary; India; Ireland; Israel; Italy; Japan; Latvia; Norway; Poland; Russia; Serbia; Slovenia; South Korea; Spain; Switzerland; Thailand; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40400262 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38368603 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37406251 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36062966 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U1111-1207-9691

Identifier Type: OTHER

Identifier Source: secondary_id

2018-000231-27

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-194773

Identifier Type: REGISTRY

Identifier Source: secondary_id

NN8640-4263

Identifier Type: -

Identifier Source: org_study_id