Clinical trial NCT03811535: 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)
Official title: A Trial Comparing the Effect and Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® in Children With Growth Hormone Deficiency
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Growth Hormone Deficiency in Children
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-01-22
Enrollment: 200
Sex: ALL
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Height Velocity: In-trial Observation Period
timeFrame: From baseline (week 0) to visit 7 (week 52)
measure: Height Velocity: On-treatment Observation Period
timeFrame: From baseline (week 0) to visit 7 (week 52)
Secondary outcomes:
measure: Change in Bone Age
timeFrame: Baseline (week -2), week 52
measure: Change in Height Standard Deviation Score (HSDS)
timeFrame: Baseline (week 0), week 52
measure: Change in Height Velocity Standard Deviation Score (HV SDS)
timeFrame: Baseline (week 0), week 52
measure: Change in Fasting Plasma Glucose (FPG) at Week 52
timeFrame: Baseline (week -2), week 52
measure: Change in FPG at Week 104
timeFrame: Baseline (week -2), week 104
measure: Change in FPG at Week 156
timeFrame: Baseline (week -2), week 156
measure: Change in FPG at Week 208
timeFrame: Baseline (week -2), week 208
measure: Change in Homeostatic Model Assessment Steady State Beta Cell Function (HOMA-B) at Week 52
timeFrame: Baseline (week -2), week 52
measure: Change in HOMA-B at Week 104
timeFrame: Baseline (week -2), week 104
measure: Change in HOMA-B at Week 156
timeFrame: Baseline (week -2), week 156
measure: Change in HOMA-B at Week 208
timeFrame: Baseline (week -2), week 208
measure: Change in Homeostatic Model Assessment Insulin Resistance (HOMA-IR) at Week 52
timeFrame: Baseline (week -2), week 52
measure: Change in HOMA-IR at Week 104
timeFrame: Baseline (week -2), week 104
measure: Change in HOMA-IR at Week 156
timeFrame: Baseline (week -2), week 156
measure: Change in HOMA-IR at Week 208
timeFrame: Baseline (week -2), week 208
measure: Change in Glycated Haemoglobin (HbA1c) at Week 52
timeFrame: Baseline (week -2), week 52
measure: Change in HbA1c at Week 104
timeFrame: Baseline (week -2), week 104
measure: Change in HbA1c at Week 156
timeFrame: Baseline (week -2), week 156
measure: Change in HbA1c at Week 208
timeFrame: Baseline (week -2), week 208
measure: Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) at Week 52
timeFrame: Baseline (week 0), week 52
measure: Change in IGF-I SDS at Week 104
timeFrame: Baseline (week 0), week 104
measure: Change in IGF-I SDS at Week 156
timeFrame: Baseline (week 0), week 156
measure: Change in IGF-I SDS at Week 208
timeFrame: Baseline (week 0), week 208
measure: Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Standard Deviation Score (SDS) at Week 52
timeFrame: Baseline (week 0), week 52
measure: Change in IGFBP-3 SDS at Week 104
timeFrame: Baseline (week 0), week 104
measure: Change in IGFBP-3 SDS at Week 156
timeFrame: Baseline (week 0), week 156
measure: Change in IGFBP-3 SDS at Week 208
timeFrame: Baseline (week 0), week 208
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of AL at Birmingham_BRM
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Orange
country: United States
facility: Children's Hosp Of Orange
state: California
city: Sacramento
country: United States
facility: Sutter Valley Med Fdt Ped Endo
state: California
city: Centennial
country: United States
facility: Rocky Mt Ped and Endo
state: Colorado
city: Greenwood Village
country: United States
facility: Ped Endo Assoc PC-G.V
state: Colorado
city: Wilmington
country: United States
facility: A.I. duPont Hospital for Children/Nemours
state: Delaware
city: Aventura
country: United States
facility: Pediatric Endocrine & Wellness Center
state: Florida
city: Atlanta
country: United States
facility: Van Meter Pediatric Endo PC
state: Georgia
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Iowa City
country: United States
facility: University OF Iowa
state: Iowa
city: Minneapolis
country: United States
facility: Univ of Minnesota M.C.H.
state: Minnesota
city: Saint Paul
country: United States
facility: Children's Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Clinics
state: Missouri
city: Las Vegas
country: United States
facility: The Docs
state: Nevada
city: Morristown
country: United States
facility: Goryeb Children's Hospital
state: New Jersey
city: Mineola
country: United States
facility: NYU Langone Hospital-LI
state: New York
city: Cincinnati
country: United States
facility: CCHMC_Cinc
state: Ohio
city: Oklahoma City
country: United States
facility: Univ Oklahoma Sci Ctr OK City
state: Oklahoma
city: Pittsburgh
country: United States
facility: UPMC Child Hosp-Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Tacoma
country: United States
facility: MultiCare Inst for Res & Innov
state: Washington
city: Algiers
country: Algeria
facility: CHU Bab El Oued Pediatrics Dept
city: Algiers
country: Algeria
facility: Endo and Diab Dept El Oued
city: Constantine
country: Algeria
facility: endocrino-diabetology department, Hospital IBN BADIS.
city: Graz
country: Austria
facility: Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie
city: Salzburg
country: Austria
facility: LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde
city: St. Poelten
country: Austria
facility: LKH St. Poelten, Kinder-und Jugendheilkunde
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Angers
country: France
facility: Centre Hospitalier Universitaire D'Angers-2
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux-Hopital Pellegrin
city: Le Kremlin-Bicetre
country: France
facility: Ap-Hp-Hopital de Bicetre-1
city: Le Kremlin-bicetre
country: France
facility: Hopital de Bicetre_Le Kremlin-Bicetre
city: MARSEILLE Cédex 05
country: France
facility: Hopital de La Timone
city: Paris
country: France
facility: Ap-Hp-Hopital Necker-2
city: Frankfurt am Main
country: Germany
facility: Endokrinologikum Frankfurt
city: Tübingen
country: Germany
facility: Universitätsklinik für Kinder und Jugendmedizin Tübingen
city: Kochi
country: India
facility: Amrita Institute Of Medical Sciences & Research Centre
state: Kerala
city: Pune
country: India
facility: Jehangir Clinical Development Centre
state: Maharashtra
city: New Dehli
country: India
facility: All India Institute of Medical Sciences
state: New Delhi
city: Dublin
country: Ireland
facility: Children's Health Ireland, Crumlin
city: Haifa
country: Israel
facility: Rambam Medical Center Children A Dept.
city: Kfar Saba
country: Israel
facility: Department of Pediatrics , Meir Medical Center
city: Petah Tikva
country: Israel
facility: Endrocrinology & DM Schneider MC
city: Zerifin
country: Israel
facility: Shamir (Assaf Harofe) Medical Center
city: Firenze
country: Italy
facility: IRCCS Meyer Firenze
city: Roma
country: Italy
facility: Bambin Gesù
city: Fukuoka-shi, Fukuoka
country: Japan
facility: Fukuoka Children's Hospital
city: Fukuyama-shi, Hiroshima
country: Japan
facility: National Hospital Organization FUKUYAMA MEDICAL CENTER
city: Fukuyama-shi, Hiroshima
country: Japan
facility: Fukuyama City Hospital
city: Kyoto
country: Japan
facility: Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
city: Mito, Ibaraki
country: Japan
facility: Ibaraki Children's Hospital
city: Nara-shi, Nara
country: Japan
facility: Nara Prefecture General Medical Center_ Nara-shi, Nara
city: Obu-shi, Aichi
country: Japan
facility: Aichi Children's Health and Medical Center
city: Okayama-shi, Okayama
country: Japan
facility: Okayama Medical Center
city: Osaka
country: Japan
facility: Osaka City General Hospital, Pediatric Endocrinology and Me
city: Osaka
country: Japan
facility: Osaka Women's and Children's Hospital
city: Shizuoka
country: Japan
facility: Hamamatsu Univ. School of Medicine Hospital, Pediatrics
city: Suita-shi, Osaka
country: Japan
facility: Osaka University Hospital_Osaka_0
city: Tokyo
country: Japan
facility: National Center for Child Health and Dev, Endo and Metabo
city: Tokyo
country: Japan
facility: Tanaka Growth Clinic
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Riga
country: Latvia
facility: Children's Clinical University Hospital
city: Szczecin
country: Poland
facility: SPSK nr 1 im Prof. T Sokolowskiego
city: Warszawa
country: Poland
facility: Instytut ''Pomnik - Centrum Zdrowia Dziecka''
city: Izhevsk
country: Russian Federation
facility: Republic Children's Hospital of Ministry of Health of Udmurt
city: Moscow
country: Russian Federation
facility: Setchenov First Moscow State Medical University
city: Moscow
country: Russian Federation
facility: RMAPE
city: Novosibirsk
country: Russian Federation
facility: Children's clinical city hospital #1
city: Rostov-on-Don
country: Russian Federation
facility: FSBEI of Higher Education "Rostov State Medical University"
city: Saint-Petersburg
country: Russian Federation
facility: SPSBHI City Children out-patient clinic #44
city: Samara
country: Russian Federation
facility: Samara Regional Children Clinical Hospital n.a. N.N. Ivanova
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Belgrade
country: Serbia
facility: University Children's Hospital Tirsova
city: Belgrade
country: Serbia
facility: Institute for Mother and Child Health Care of Serbia
city: Novi Sad
country: Serbia
facility: Institute for Health Care of Children and Adolescents
city: Ljubljana
country: Slovenia
facility: University Children's Hospital
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago de Compostela
state: A Coruña
city: Esplugues Llobregat(Barcelona)
country: Spain
facility: Hospital Sant Joan de Déu
city: Bern
country: Switzerland
facility: Med. Kinder- und Poliklinik
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial hospital-Ped-Endocrinology
city: Bangkok
country: Thailand
facility: Phramongkutklao Hospital - Paediatrics Endocrinology Centre
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Children Clincial Hospital_Lubyanka
city: Kyiv
country: Ukraine
facility: Institute of Endocrinology and Metabolism of AMSU
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Med University based on RegionalEndocrinDispensary
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital_Cambridge
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary_Hull
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Tooting
country: United Kingdom
facility: St Georges Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References:
citation: 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.