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) (REAL4)

March 12, 2024 updated by: Novo Nordisk A/S

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.

Study Overview

Status

Active, not recruiting

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Algiers, Algeria, 16000
        • CHU Bab El Oued Pediatrics Dept
      • Algiers, Algeria, 16000
        • Endo and Diab Dept El Oued
      • Constantine, Algeria, 25000
        • endocrino-diabetology department, Hospital IBN BADIS.
      • Graz, Austria, 8036
        • Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie
      • Salzburg, Austria, A 5020
        • LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde
      • St. Poelten, Austria, A 3100
        • LKH St. Poelten, Kinder-und Jugendheilkunde
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • Stollery's Children Hospital
      • Tallinn, Estonia, 13419
        • Tallinn Children's Hospital
      • Tartu, Estonia, 50406
        • Tartu University Hospital Children's Clinic
      • Angers, France, 49100
        • Centre Hospitalier Universitaire D'Angers-2
      • Bordeaux, France, 33000
        • Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
      • Le Kremlin-Bicetre, France, 94270
        • Ap-Hp-Hopital de Bicetre-1
      • Le Kremlin-bicetre, France, 94275
        • Hopital de Bicetre_Le Kremlin-Bicetre
      • MARSEILLE Cédex 05, France, 13385
        • Hopital de La Timone
      • Paris, France, 75015
        • Ap-Hp-Hopital Necker-2
      • Frankfurt am Main, Germany, 60596
        • Endokrinologikum Frankfurt
      • Tübingen, Germany, 72076
        • Universitätsklinik für Kinder und Jugendmedizin Tübingen
      • Ulm, Germany, 89075
        • Universitätsklinikum Ulm für Kinder- und Jugendmedizin
    • 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
      • Dublin, Ireland, D12 N512
        • Children's Health Ireland, Crumlin
      • Haifa, Israel, 31096
        • Rambam Medical Center Children A Dept.
      • Kfar Saba, Israel, 44281
        • Department of Pediatrics , Meir Medical Center
      • Petah Tikva, Israel, 49202
        • Endrocrinology & DM Schneider MC
      • Zerifin, Israel, 70300
        • Shamir (Assaf Harofe) Medical Center
      • Firenze, Italy, 50139
        • AOU Meyer
      • Roma, Italy, 00165
        • Bambin Gesù
      • Fukuoka-shi, Fukuoka, Japan, 813-0017
        • Fukuoka Children's Hospital
      • Fukuyama-shi, Hiroshima, Japan, 720-8520
        • National Hospital Organization FUKUYAMA MEDICAL CENTER
      • Fukuyama-shi, Hiroshima, Japan, 721-8511
        • Fukuyama City Hospital
      • Kyoto, Japan, 602-8566
        • Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
      • Mito, Ibaraki, Japan, 311-4145
        • Ibaraki Children's Hospital
      • Nara-shi, Nara, Japan, 630-8581
        • Nara Prefecture General Medical Center_ Nara-shi, Nara
      • Obu-shi, Aichi, Japan, 474-8710
        • Aichi Children's Health and Medical Center
      • Okayama-shi, Okayama, Japan, 701-1192
        • Okayama Medical Center
      • Osaka, Japan, 534-0021
        • Osaka City General Hospital, Pediatric Endocrinology and Me
      • Osaka, Japan, 594-1101
        • Osaka Women's and Children's Hospital
      • Shizuoka, Japan, 431-3192
        • Hamamatsu Univ. School of Medicine Hospital, Pediatrics
      • Suita-shi, Osaka, Japan, 565-0871
        • Osaka University Hospital_Osaka_0
      • Tokyo, Japan, 157 8535
        • National Center for Child Health and Dev, Endo and Metabo
      • Tokyo, Japan, 158-0097
        • Tanaka Growth Clinic
      • Busan, Korea, Republic of, 47392
        • Inje University Busan Paik Hospital
      • Daegu, Korea, Republic of, 41944
        • Kyungpook National University Hospital
      • Gyeonggi-do, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Gyeonggi-do, Korea, Republic of, 16499
        • Ajou University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Riga, Latvia, LV1004
        • Children's Clinical University Hospital
      • Szczecin, Poland, 71-252
        • SPSK nr 1 im Prof. T Sokolowskiego
      • Warszawa, Poland, 04-730
        • Instytut ''Pomnik - Centrum Zdrowia Dziecka''
    • Podkarpackie Voivodeship
      • Rzeszow, Podkarpackie Voivodeship, Poland, 35-301
        • Kliniczny Szpital Wojewodzki nr 2 im. Sw. Jadwigi Krolowej w Rzeszowie
      • Izhevsk, Russian Federation, 426009
        • Republic Children's Hospital of Ministry of Health of Udmurt
      • Moscow, Russian Federation, 119435
        • Setchenov First Moscow State Medical University
      • Moscow, Russian Federation, 125373
        • RMAPE
      • Novosibirsk, Russian Federation, 630048
        • Children's clinical city hospital #1
      • Rostov-on-Don, Russian Federation, 344013
        • FSBEI of Higher Education "Rostov State Medical University"
      • Saint-Petersburg, Russian Federation, 191144
        • SPSBHI City Children out-patient clinic #44
      • Samara, Russian Federation, 443079
        • Samara Regional Children Clinical Hospital n.a. N.N. Ivanova
      • Tomsk, Russian Federation, 634050
        • Siberian State Medical University
      • Belgrade, Serbia, 11000
        • University Children's Hospital Tirsova
      • Belgrade, Serbia, 11070
        • Institute for Mother and Child Health Care of Serbia
      • Novi Sad, Serbia, 21000
        • Institute for Health Care of Children and Adolescents
      • Ljubljana, Slovenia, 1525
        • PeK - Dept. of Paediatric Endocrinology, Diabetes and Metabolism
      • Esplugues Llobregat(Barcelona), Spain, 08950
        • Hospital Sant Joan de Déu
      • Santiago de Compostela, Spain, 15706
        • Hospital Clínico de Santiago de Compostela
      • Bern, Switzerland, 3010
        • Med. Kinder- und Poliklinik
      • Bangkok, Thailand, 10330
        • King Chulalongkorn Memorial hospital-Ped-Endocrinology
      • Bangkok, Thailand, 10400
        • Phramongkutklao Hospital - Paediatrics Endocrinology Centre
      • Kharkiv, Ukraine, 61000
        • Kharkiv Regional Children Clincial Hospital_Lubyanka
      • Kyiv, Ukraine, 04114
        • Institute of Endocrinology and Metabolism of AMSU
      • Vinnytsia, Ukraine, 21010
        • Vinnytsia Med University based on RegionalEndocrinDispensary
      • Cambridge, United Kingdom, CB2 0QQ
        • Addenbrooke's Hospital_Cambridge
      • Hull, United Kingdom, HU3 2JZ
        • Hull Royal Infirmary_Hull
      • Liverpool, United Kingdom, L12 2AP
        • Alder Hey Children's Hospital
      • Manchester, United Kingdom, M13 9WL
        • Royal Manchester Children's Hospital
      • Tooting, United Kingdom, SW17 0RE
        • St Georges Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Univ of AL at Birmingham_BRM
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hosp-Los Angeles
      • Orange, California, United States, 92868
        • Children's Hosp Of Orange
      • Sacramento, California, United States, 95821
        • Ctr of Exclnce in Diab and Endo
    • 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
        • A.I. duPont Hospital for Children/Nemours
    • Florida
      • Aventura, Florida, United States, 33180
        • Pediatric Endocrine & Wellness Center
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Van Meter Pediatric Endo PC
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • Univ of Minnesota M.C.H.
      • Saint Paul, Minnesota, United States, 55102
        • Children's Minnesota
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Children's Mercy Clinics
    • Nevada
      • Las Vegas, Nevada, United States, 89113
        • The Docs
    • New Jersey
      • Morristown, New Jersey, United States, 07962
        • Goryeb Children's Hospital
    • New York
      • Mineola, New York, United States, 11501
        • NYU Langone Hospital-LI
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • CCHMC_Cinc
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Univ Oklahoma Sci Ctr OK City
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • UPMC Child Hosp-Pittsburgh
    • Texas
      • Austin, Texas, United States, 78723
        • Dell Children's Medical Center
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
    • Washington
      • Tacoma, Washington, United States, 98405
        • MultiCare Inst for Res & Innov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 11 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
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.
Active Comparator: Norditropin® daily
Participants will receive Norditropin® daily for 52 weeks (main trial period).
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From baseline (week 0) to visit 7 (week 52)
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.
From baseline (week 0) to visit 7 (week 52)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Bone Age
Time Frame: Baseline (week -2), week 52
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.
Baseline (week -2), week 52
Change in Height Standard Deviation Score (HSDS)
Time Frame: Baseline (week 0), week 52
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.
Baseline (week 0), week 52
Change in Height Velocity Standard Deviation Score (HV SDS)
Time Frame: Baseline (week 0), week 52
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.
Baseline (week 0), week 52
Change in Fasting Plasma Glucose (FPG) at Week 52
Time Frame: Baseline (week -2), week 52
Change from baseline (week -2) in FPG at week 52 is presented.
Baseline (week -2), week 52
Change in FPG at Week 104
Time Frame: Baseline (week -2), week 104
Baseline (week -2), week 104
Change in FPG at Week 156
Time Frame: Baseline (week -2), week 156
Baseline (week -2), week 156
Change in FPG at Week 208
Time Frame: Baseline (week -2), week 208
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 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.
Baseline (week -2), week 52
Change in HOMA-B at Week 104
Time Frame: Baseline (week -2), week 104
Baseline (week -2), week 104
Change in HOMA-B at Week 156
Time Frame: Baseline (week -2), week 156
Baseline (week -2), week 156
Change in HOMA-B at Week 208
Time Frame: Baseline (week -2), week 208
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 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.
Baseline (week -2), week 52
Change in HOMA-IR at Week 104
Time Frame: Baseline (week -2), week 104
Baseline (week -2), week 104
Change in HOMA-IR at Week 156
Time Frame: Baseline (week -2), week 156
Baseline (week -2), week 156
Change in HOMA-IR at Week 208
Time Frame: Baseline (week -2), week 208
Baseline (week -2), week 208
Change in Glycated Haemoglobin (HbA1c) at Week 52
Time Frame: Baseline (week -2), week 52
Change from baseline (week -2) in HbA1c at week 52 is presented.
Baseline (week -2), week 52
Change in HbA1c at Week 104
Time Frame: Baseline (week -2), week 104
Baseline (week -2), week 104
Change in HbA1c at Week 156
Time Frame: Baseline (week -2), week 156
Baseline (week -2), week 156
Change in HbA1c at Week 208
Time Frame: Baseline (week -2), week 208
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 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.
Baseline (week 0), week 52
Change in IGF-I SDS at Week 104
Time Frame: Baseline (week 0), week 104
Baseline (week 0), week 104
Change in IGF-I SDS at Week 156
Time Frame: Baseline (week 0), week 156
Baseline (week 0), week 156
Change in IGF-I SDS at Week 208
Time Frame: Baseline (week 0), week 208
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 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.
Baseline (week 0), week 52
Change in IGFBP-3 SDS at Week 104
Time Frame: Baseline (week 0), week 104
Baseline (week 0), week 104
Change in IGFBP-3 SDS at Week 156
Time Frame: Baseline (week 0), week 156
Baseline (week 0), week 156
Change in IGFBP-3 SDS at Week 208
Time Frame: Baseline (week 0), week 208
Baseline (week 0), week 208

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2019

Primary Completion (Actual)

November 10, 2021

Study Completion (Estimated)

September 30, 2025

Study Registration Dates

First Submitted

January 18, 2019

First Submitted That Met QC Criteria

January 18, 2019

First Posted (Actual)

January 22, 2019

Study Record Updates

Last Update Posted (Actual)

March 13, 2024

Last Update Submitted That Met QC Criteria

March 12, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • NN8640-4263
  • U1111-1207-9691 (Other Identifier: World Health Organization (WHO))
  • 2018-000231-27 (Other Identifier: European Medicines Agency (EudraCT))
  • JapicCTI-194773 (Registry Identifier: JAPIC (Japan))

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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