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)

Growth Hormone Deficiency in Children Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03811535
• Other study ID #: NN8640-4263
• Secondary ID: U1111-1207-96912
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 20, 2019
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: September 30, 2025
• Est. primary completion date: November 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Growth Hormone Deficiency in Children

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Algeria	CHU Bab El Oued Pediatrics Dept	Algiers
Algeria	Endo and Diab Dept El Oued	Algiers
Algeria	endocrino-diabetology department, Hospital IBN BADIS.	Constantine
Austria	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	St. Poelten
Canada	Stollery Children's Hospital	Edmonton	Alberta
France	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-Bicetre
France	Hopital de Bicetre_Le Kremlin-Bicetre	Le Kremlin-bicetre
France	Hopital de La Timone	MARSEILLE Cédex 05
France	Ap-Hp-Hopital Necker-2	Paris
Germany	Endokrinologikum Frankfurt	Frankfurt am Main
Germany	Universitätsklinik für Kinder und Jugendmedizin Tübingen	Tübingen
Germany	Universitätsklinikum Ulm für Kinder- und Jugendmedizin	Ulm
India	Amrita Institute Of Medical Sciences & Research Centre	Kochi	Kerala
India	All India Institute of Medical Sciences	New Dehli	New Delhi
India	Jehangir Clinical Development Centre	Pune	Maharashtra
Ireland	Children's Health Ireland, Crumlin	Dublin
Israel	Rambam Medical Center Children A Dept.	Haifa
Israel	Department of Pediatrics , Meir Medical Center	Kfar Saba
Israel	Endrocrinology & DM Schneider MC	Petah Tikva
Israel	Shamir (Assaf Harofe) Medical Center	Zerifin
Italy	AOU Meyer	Firenze
Italy	Bambin Gesù	Roma
Japan	Fukuoka Children's Hospital	Fukuoka-shi, Fukuoka
Japan	Fukuyama City Hospital	Fukuyama-shi, Hiroshima
Japan	National Hospital Organization FUKUYAMA MEDICAL CENTER	Fukuyama-shi, Hiroshima
Japan	Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics	Kyoto
Japan	Ibaraki Children's Hospital	Mito, Ibaraki
Japan	Nara Prefecture General Medical Center_ Nara-shi, Nara	Nara-shi, Nara
Japan	Aichi Children's Health and Medical Center	Obu-shi, Aichi
Japan	Okayama Medical Center	Okayama-shi, Okayama
Japan	Osaka City General Hospital, Pediatric Endocrinology and Me	Osaka
Japan	Osaka Women's and Children's Hospital	Osaka
Japan	Hamamatsu Univ. School of Medicine Hospital, Pediatrics	Shizuoka
Japan	Osaka University Hospital_Osaka_0	Suita-shi, Osaka
Japan	National Center for Child Health and Dev, Endo and Metabo	Tokyo
Japan	Tanaka Growth Clinic	Tokyo
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Latvia	Children's Clinical University Hospital	Riga
Poland	SPSK nr 1 im Prof. T Sokolowskiego	Szczecin
Poland	Instytut ''Pomnik - Centrum Zdrowia Dziecka''	Warszawa
Russian Federation	Republic Children's Hospital of Ministry of Health of Udmurt	Izhevsk
Russian Federation	RMAPE	Moscow
Russian Federation	Setchenov First Moscow State Medical University	Moscow
Russian Federation	Children's clinical city hospital #1	Novosibirsk
Russian Federation	FSBEI of Higher Education "Rostov State Medical University"	Rostov-on-Don
Russian Federation	SPSBHI City Children out-patient clinic #44	Saint-Petersburg
Russian Federation	Samara Regional Children Clinical Hospital n.a. N.N. Ivanova	Samara
Russian Federation	Siberian State Medical University	Tomsk
Serbia	Institute for Mother and Child Health Care of Serbia	Belgrade
Serbia	University Children's Hospital Tirsova	Belgrade
Serbia	Institute for Health Care of Children and Adolescents	Novi Sad
Slovenia	PeK - Dept. of Paediatric Endocrinology, Diabetes and Metabolism	Ljubljana
Spain	Hospital Sant Joan de Déu	Esplugues Llobregat(Barcelona)
Spain	Hospital Clínico de Santiago de Compostela	Santiago de Compostela
Switzerland	Med. Kinder- und Poliklinik	Bern
Thailand	King Chulalongkorn Memorial hospital-Ped-Endocrinology	Bangkok
Thailand	Phramongkutklao Hospital - Paediatrics Endocrinology Centre	Bangkok
Ukraine	Kharkiv Regional Children Clincial Hospital_Lubyanka	Kharkiv
Ukraine	Institute of Endocrinology and Metabolism of AMSU	Kyiv
Ukraine	Vinnytsia Med University based on RegionalEndocrinDispensary	Vinnytsia
United Kingdom	Addenbrooke's Hospital_Cambridge	Cambridge
United Kingdom	Hull Royal Infirmary_Hull	Hull
United Kingdom	Alder Hey Children's Hospital	Liverpool
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	St Georges Hospital	Tooting
United States	Van Meter Pediatric Endo PC	Atlanta	Georgia
United States	Dell Children's Medical Center	Austin	Texas
United States	Pediatric Endocrine & Wellness Center	Aventura	Florida
United States	Univ of AL at Birmingham_BRM	Birmingham	Alabama
United States	Rocky Mt Ped and Endo	Centennial	Colorado
United States	CCHMC_Cinc	Cincinnati	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Ped Endo Assoc PC-G.V	Greenwood Village	Colorado
United States	Riley Hospital For Children	Indianapolis	Indiana
United States	University OF Iowa	Iowa City	Iowa
United States	Children's Mercy Clinics	Kansas City	Missouri
United States	The Docs	Las Vegas	Nevada
United States	Children's Hosp-Los Angeles	Los Angeles	California
United States	NYU Langone Hospital-LI	Mineola	New York
United States	Univ of Minnesota M.C.H.	Minneapolis	Minnesota
United States	Goryeb Children's Hospital	Morristown	New Jersey
United States	Univ Oklahoma Sci Ctr OK City	Oklahoma City	Oklahoma
United States	Children's Hosp Of Orange	Orange	California
United States	UPMC Child Hosp-Pittsburgh	Pittsburgh	Pennsylvania
United States	Sutter Valley Med Fdt Ped Endo	Sacramento	California
United States	Children's Minnesota	Saint Paul	Minnesota
United States	MultiCare Inst for Res & Innov	Tacoma	Washington
United States	A.I. duPont Hospital for Children/Nemours	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Algeria,  Austria,  Canada,  France,  Germany,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Poland,  Russian Federation,  Serbia,  Slovenia,  Spain,  Switzerland,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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.	Baseline (week -2), week 52
Secondary	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.	Baseline (week 0), week 52
Secondary	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.	Baseline (week 0), week 52
Secondary	Change in Fasting Plasma Glucose (FPG) at Week 52	Change from baseline (week -2) in FPG at week 52 is presented.	Baseline (week -2), week 52
Secondary	Change in FPG at Week 104		Baseline (week -2), week 104
Secondary	Change in FPG at Week 156		Baseline (week -2), week 156
Secondary	Change in FPG at Week 208		Baseline (week -2), week 208
Secondary	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.	Baseline (week -2), week 52
Secondary	Change in HOMA-B at Week 104		Baseline (week -2), week 104
Secondary	Change in HOMA-B at Week 156		Baseline (week -2), week 156
Secondary	Change in HOMA-B at Week 208		Baseline (week -2), week 208
Secondary	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.	Baseline (week -2), week 52
Secondary	Change in HOMA-IR at Week 104		Baseline (week -2), week 104
Secondary	Change in HOMA-IR at Week 156		Baseline (week -2), week 156
Secondary	Change in HOMA-IR at Week 208		Baseline (week -2), week 208
Secondary	Change in Glycated Haemoglobin (HbA1c) at Week 52	Change from baseline (week -2) in HbA1c at week 52 is presented.	Baseline (week -2), week 52
Secondary	Change in HbA1c at Week 104		Baseline (week -2), week 104
Secondary	Change in HbA1c at Week 156		Baseline (week -2), week 156
Secondary	Change in HbA1c at Week 208		Baseline (week -2), week 208
Secondary	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.	Baseline (week 0), week 52
Secondary	Change in IGF-I SDS at Week 104		Baseline (week 0), week 104
Secondary	Change in IGF-I SDS at Week 156		Baseline (week 0), week 156
Secondary	Change in IGF-I SDS at Week 208		Baseline (week 0), week 208
Secondary	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.	Baseline (week 0), week 52
Secondary	Change in IGFBP-3 SDS at Week 104		Baseline (week 0), week 104
Secondary	Change in IGFBP-3 SDS at Week 156		Baseline (week 0), week 156
Secondary	Change in IGFBP-3 SDS at Week 208		Baseline (week 0), week 208