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CTRI Number  CTRI/2023/03/050330 [Registered on: 03/03/2023] Trial Registered Prospectively
Last Modified On: 19/06/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Study to know the safety and efficacy of once once weekly dosing of somapacitan with daily Norditropin in children with short stature either born small for gestational age or with Turner syndrome, Noonan syndrome, or idiopathic short stature 
Scientific Title of Study   A study comparing the effect and safety of once weekly dosing of somapacitan with daily Norditropin® as well as evaluating long-term safety of somapacitan in a basket study design in children with short stature either born small for gestational age or with Turner syndrome, Noonan syndrome, or idiopathic short stature 
Trial Acronym  REAL 8 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
2021-005607-13  EudraCT 
NN8640-4467 Version 7.0 dated 22 March 2023  Protocol Number 
U1111-1270-0862  UTN 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
Modification(s)  
Name  Dr Maya Sharma 
Designation  Vice President - Clinical, Medical, Regulatory & Pharmacovigilance 
Affiliation  Novo Nordisk India Private Limited 
Address  Novo Nordisk India Private Limited
Nxt Tower - 2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli
Bangalore
KARNATAKA
560045
India 
Phone  9911497869  
Fax  080-41123518  
Email  yrms@novonordisk.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Dr Maya Sharma 
Designation  Vice President - Clinical, Medical, Regulatory & Pharmacovigilance 
Affiliation  Novo Nordisk India Private Limited 
Address  Novo Nordisk India Private Limited
Nxt Tower - 2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli
Bangalore
KARNATAKA
560045
India 
Phone  9911497869  
Fax  080-41123518  
Email  yrms@novonordisk.com  
 
Source of Monetary or Material Support
Modification(s)  
Novo Nordisk AS, Novo Allé, 2880 Bagsvaerd Denmark 
 
Primary Sponsor
Modification(s)  
Name  Novo Nordisk India Private Limited 
Address  Nxt Tower - 2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India Tel No.: 080-40303200 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NA  NA 
 
Countries of Recruitment     Austria
Belgium
Brazil
Bulgaria
Canada
China
Croatia
Finland
France
Germany
Greece
India
Ireland
Israel
Italy
Japan
Latvia
Malaysia
Mexico
Netherlands
Poland
Portugal
Republic of Korea
Russian Federation
Saudi Arabia
Serbia
Slovenia
South Africa
Spain
Switzerland
Thailand
United Kingdom
United States of America  
Sites of Study  
No of Sites = 3  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Rajesh Khadgawat  All India Institute of Medical Sciences (AIIMS)  Room 303, Biotechnology Block, Dept of Endocrinology, Ansari Nagar
New Delhi
DELHI 		 9891418190

rajeshkhadgawat@hotmail.com 
Dr Praveen Valliyaparambil Pavithran  Amrita Institute of Medical Sciences & Research Centre  Dept of Endocrinology and Diabetes, AIMS Ponekkara.P.O,Kochi
Ernakulam
KERALA 		 9495247676

praveenvp@aims.amrita.edu 
Dr Vaman Khadilkar  Jehangir Clinical Development Centre Pvt. Ltd  Jehangir Hospital Premises , 32 , Sassoon Road
Pune
MAHARASHTRA 		 9860027285

vamankhadilkar@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 3  
Name of Committee  Approval Status 
Ethics Committee Jehangir clinical development centre Pvt Ltd  Approved 
Institute Ethics Committee AIIMS  Approved 
Institute Ethics Committee Amrita institute of medical sciences  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: E368||Other intraoperative complicationsof endocrine system,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Comparator Agent  Norditropin  Norditropin® will be administered s.c. once daily using FlexPro® pen-injector.Participants will receive Norditropin® for 52 weeks (main treatment period) and Somapacitan for 221 weeks (extension period) 
Intervention  Somapacitan  Somapacitan will be administered subcutaneously (s.c.) once weekly using PDS290 pen-injector. Participants will receive Somapacitan for 273 weeks. 
 
Inclusion Criteria
Modification(s)  
Age From  30.00 Month(s)
Age To  11.00 Year(s)
Gender  Both 
Details  1. Informed consent of parent or legally acceptable representative of participant and child assent, as age appropriate must be obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
2. No prior exposure to growth promoting therapy, including but not limited to growth hormone, IGF-I and ghrelin analogues

Applicable to children with SGA:
3. Born small for gestational age (birth length below -2 SDS OR birth weight below -2 SDS OR both) (according to national standards).
4. Prepubertal children:
a. Boys:
- Age above or equal to 2 years and 26 weeks and below 11.0 years at screening.
- Testis volume below 4 mL
b. Girls:
- Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
- Tanner stage 1 for breast development: No palpable glandular breast tissue)
5. Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
6. Impaired height velocity defined as annualized height velocity below the 50th percentile for chronological age and sex according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening.
7. Body Mass Index below the 95th percentile according to Centers for Disease Control and Prevention, Body Mass Index-for-age growth charts.

Applicable to girls with TS:
8. Confirmed diagnosis of TS by 30-cell (or more) lymphocyte chromosomal analysis.*
9. Prepubertal girls:
- Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
- Tanner stage 1 for breast development: No palpable glandular breast tissue)
10. Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
11. Historical height measured 6-18 months prior to screening.
12. Thyroid hormone replacement therapy should be adequate and stable for at least 90 days prior to randomization, if applicable.

Applicable to children with NS:
13. Clinical diagnosis of NS according to van der Burgt score list
14. Prepubertal children:
a. Boys:
- Age above or equal to 2 years and 26 weeks and below 11.0 years at screening.
- Testis volume below 4 mL
b. Girls:
- Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
- Tanner stage 1 for breast development: No palpable glandular breast tissue)
15. Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
16. Historical height measured 6-18 months prior to screening.
17. Thyroid hormone replacement therapy should be adequate and stable for at least 90 days prior to randomization, if applicable.
Applicable to children with ISS:
18. Prepubertal children:
a. Boys:
- Age above or equal to 2 years and 26 weeks and below 11.0 years at screening.
- Testis volume below 4 mL
b. Girls:
- Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
- Tanner stage 1 for breast development: No palpable glandular breast tissue)
19. Bone age:
a. Boys:
- Bone age below or equal to 12 years.
- Bone age not delayed or advanced more than 2 years compared to chronological age.
b. Girls:
- Bone age below or equal to 11 years.
- Bone age not delayed or advanced more than 2 years compared to chronological age.
20. Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
21. Historical height measured 6-18 months prior to screening.
22. One normal GH secretion (GH peak above 7 ng/mL) during GH stimulation test performed within 18 months prior to screening or if such a test is not available for children with ISS, a test should be performed as part of the screening assessments and the result must be available prior to randomization.
- If a 30-cell count is not available for patients with TS, a test should be done, and results must be available prior to randomization.
 
 
ExclusionCriteria 
Details  1. Known or suspected hypersensitivity to study intervention(s) or related products.
2. Previous randomisation into same sub-study in this study.
3. Receipt of any investigational medicinal product within 3 months before screening or participation in another clinical study at the time of randomisation
Children with suspected or confirmed growth hormone deficiency according to local practice.
5. Children diagnosed with diabetes mellitus or screening values from the central laboratory of
a. fasting plasma glucose above or equal to 126 mg/dL (7.0 mmol/L) or
b. HbA1c above or equal to 6.5%.
6. Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening.
7. Children requiring inhaled glucocorticoid therapy at a dose greater than 400 microg/day of inhaled budesonide or equivalent (i.e., 250 microg/day for fluticasone propionate) for longer than 4 consecutive weeks within the last 12 months prior to screening.
8. 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 (ADHD).
9. Diagnosis of attention deficit hyperactivity disorder (ADHD).
10. History or known presence of malignancy including intracranial tumours.
11. History or known presence of active Hepatitis B or Hepatitis C (exceptions to this exclusion criterion is the presence of antibodies due to vaccination against Hepatitis B).
12. Any disorder, which in the investigators opinion, might jeopardise participants safety or compliance with the protocol.
13. The participant or the parent/legally acceptable representative is likely to be non-compliant in respect to study conduct, as judged by the investigator.
14. Current treatment with sex hormones or aromatase inhibitors.
15. Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements, such as, but not limited to:
1. Known family history of skeletal dysplasia.
2. Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
3. Any other disorder/condition that can cause short stature such as, but not limited to, psychosocial deprivation, nutritional disorders, chronic systemic illness and chronic renal disease.

Applicable to children with SGA:
1. TS (including mosaicism)
2. NS.
3. Hormonal deficiencies.
4. Children who are small due to malnutrition defined as -2 standard deviations according to standards. 0-5 years: weight for height on World Health Organisation Multicentre Growth Reference Study 2006. Above 5 years: World Health Organisation 2007 Body Mass Index.
5. Known chromosomal aneuploidy or significant gene mutations causing medical syndromes with short stature, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, skeletal dysplasias, abnormal SHOX gene analysis or absence of GH receptors.

Applicable to children with TS:
1. NS
2. Mosaicism below 10%.
3. TS with Y-chromosome mosaicism where gonadectomy has not been performed.
4. NYHA class II or above or requiring medication for any heart condition.
5. Coeliac disease where participant is not stable on gluten free diet for the previous 12 months prior to screening.

Applicable to children with NS:
1. TS (including mosaicism)
2. Noonan-related disorders: Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome), Noonan syndrome with loose anagen hair, cardiofaciocutaneous syndrome (CFC), Costello syndrome, neurofibromatosis type 1 (NF1) and Legius syndrome. Molecular genetic testing results must be available prior to randomisation to exclude these.
3. Coeliac disease where participant is not stable on gluten free diet for the previous 12 months prior to screening.

Applicable to children with ISS:
1. TS (including mosaicism)
2. NS
3. Hormonal deficiencies.
4. Born small for gestational age (defined as birth length below -2 SDS OR birth weight below -2 SDS OR both) (according to national standards).
5. Known chromosomal aneuploidy or significant gene mutations causing medical syndromes with short stature, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, skeletal dysplasias, abnormal SHOX gene analysis or absence of GH receptors.

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To confirm non-inferiority of
once-weekly somapacitan
compared with once-daily
Norditropin® in terms of
longitudinal growth measured by height velocity at week 52 in children with each of the four indications: SGA, TS, NS or ISS 		 From baseline (week 0) to visit 7 (week 52). 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate once-weekly somapacitan compared with
once-daily Norditropin® in terms of other aspects of longitudinal growth in children with each of
the four indications: SGA, TS,
NS or ISS. 		 From baseline (week
0) to visit 7 (week
52) 
To evaluate safety of onceweekly somapacitan compared with once-daily Norditropin® in terms of safety parameters measured by glucose metabolism
in children with each of the four indications: SGA, TS, NS or ISS 		 From screening
(visit 1) to visit 7
(week 52) 
To evaluate the steady state pharmacokinetics of once-weekly somapacitan in children with each of the four indications: SGA, TS, NS or ISS  From visit 3 (week 4) to visit 7 (week 52). 
To evaluate long-term safety of once-weekly somapacitan in terms of safety parameters measured by glucose metabolism in children with each of the four indications: SGA, TS, NS or ISS  From screening (visit 1) to visit 15 (week 156). 
 
Target Sample Size
Modification(s)  		 Total Sample Size="412"
Sample Size from India="16" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)
Modification(s)  		 20/04/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  02/09/2022 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial
Modification(s)  		 Years="3"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Closed to Recruitment of Participants 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details   NA 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary
Modification(s)  		 The study compares two medicines for treatment of children born small and who stay small, or with Turner Syndrome, Noonan Syndrome, or idiopathic short stature. The purpose of the study is to see how well treatment with somapacitan works compared to treatment with Norditropin®. Somapacitan is a new medicine, and Norditropin® is a medicine doctors can already prescribe in some countries. The study will last for about 3 years. The participants will either get somapacitan once a week for 3 years or Norditropin® once a day for 1 year followed by somapacitan once a week for 2 years. Which treatment the participants get is decided by chance. 
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