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CTRI Number  CTRI/2017/08/009359 [Registered on: 14/08/2017] Trial Registered Prospectively
Last Modified On: 20/05/2022
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 on Treatment of children with growth failure with weekly or daily doses of growth hormone 
Scientific Title of Study
Modification(s)  		 A Phase 3, Open-Label, Randomized, Multicenter, 12 Months, Efficacy And Safety Study Of Weekly Mod-4023 Compared To Daily Genotropin® Therapy In Pre-Pubertal Children With Growth Hormone Deficiency And A 12-Month Open-Label Extension To Assess The Efficacy And Safety Of Mod-4023.  
Trial Acronym  None 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
CP-4-006, Version 2.0 dated 09 Mar 2022  Protocol Number 
NCT02968004  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr Jayashri Krishnan 
Designation  Head - Operations 
Affiliation  JSS Medical Research Asia Pacific Private Ltd. 
Address  JSS Medical Research Asia Pacific Private Ltd. A-39, Hindu colony, 5th Cross Street, Nanganallur

Chennai
TAMIL NADU
600061
India 
Phone  91-9771407484  
Fax  91-044-43588940  
Email  jayashri.krishnan@jssresearch.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Sonika Newar 
Designation  Medical Monitor 
Affiliation  JSS Medical Research India Private Limited 
Address  JSS Medical Research India Private Limited, 6th Floor, Vatika Mindscapes (Tower B), Plot 12/2, Sector 27D

Faridabad
HARYANA
121003
India 
Phone  91-8800799887  
Fax  91-129-6613520  
Email  sonika.newar@jssresearch.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Dr Jayashri Krishnan 
Designation  Head - Operations 
Affiliation  JSS Medical Research Asia Pacific Private Ltd. 
Address  JSS Medical Research Asia Pacific Private Ltd. A-39, Hindu colony, 5th Cross Street, Nanganallur

Chennai
TAMIL NADU
600061
India 
Phone  91-9771407484  
Fax  91-044-43588940  
Email  jayashri.krishnan@jssresearch.com  
 
Source of Monetary or Material Support  
OPKO Biologics Ltd. 16 Ashlegan St., Kiryat Gat 8211804, Israel 
 
Primary Sponsor  
Name  OPKO Biologics Ltd 
Address  16 Ashlegan St., Kiryat Gat 8211804, Israel 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
None   
 
Countries of Recruitment     Argentina
Australia
Belarus
Brazil
Bulgaria
Canada
Chile
Colombia
France
Georgia
Germany
Greece
India
Israel
Italy
Mexico
New Zealand
Poland
Romania
Russian Federation
Serbia
Spain
Taiwan
Turkey
Ukraine
United Kingdom
United States of America
Viet Nam
Republic of Korea  
Sites of Study  
No of Sites = 14  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Rajesh Khadgawat  All India Institute of Medical Sciences  Department of Endocrinology & Metabolism, Ansari Nagar East, Gautam Nagar, New Delhi- 110029
New Delhi
DELHI 		 91-9822436184
91-11-26588641
rajeshkhadgawat@hotmail.com 
Dr Kumaravel Velayutham  Apollo Specialty Hospitals  Ground Floor, Department of Pediatric Endocrinology, Lake View Road, K.K. Nagar, Madurai - 625020
Madurai
TAMIL NADU 		 91-9940582328
91-45-22312223
drvkumaravel@gmail.com 
Dr Kirtikumar Dharmshibhai Modi  Care Hospital  5-4-199, Jawaharlal Nehru Road, Exhibition Grounds Road, Nampally Hyderabad, Telangana - 500001
Hyderabad
ANDHRA PRADESH 		 91-9848115322
91-40-24608525
drkdmodi@yahoo.co.in 
Dr Parag Shah  Dr. Jivraj Mehta Smarak Health Foundation  Bakeri Medical Research Centre, Ratubhai Adani Arogyadham, Jivraj Mehta Marg, Nr. Ayojan Nagar, Ahmedabad- 380007
Ahmadabad
GUJARAT 		 91-9824042688
91-79-26601411
paragendocrine@yahoo.com 
Dr Jayashri Shembalkar  Getwell Hospital and Research Institute  Department of Endocrinology. Ground Floor 20/1, Dr. Khare Marg, Dhantoli, Nagpur - 440012
Nagpur
MAHARASHTRA 		 91-9665013901
91-712-6645017
pkshembalkar@hotmail.com 
Dr Vijay Warad  Inamdar Multispecialty Hospital  Building, No 15, Fatima Nagar, Pune- 411040
Pune
MAHARASHTRA 		 91-9822436184
91-20-66812485
vijaypwarad@gmail.com 
Dr Apurba Ghosh  Institute of Child Health  11 Dr. Biresh Guha Street, Kolkata -700017
Kolkata
WEST BENGAL 		 91-9830052887
91-33-22905686
apurbaghosh@yahoo.com 
Dr Vaman Khadilkar  Jehangir Clinical Development Centre  Jehangir Hospital Premises, 32 Sassoon Road, Pune- 411001
Pune
MAHARASHTRA 		 91-9860027285
91-20-26059319
vamankhadilkar@gmail.com 
Dr Mala Dharmalingam  M.S.Ramaiah Medical College and Hospitals  1st Floor, M.S.Ramaiah Advanced Learning Centre, Gnanagangothri campus, Gate-4, New BEL Road, MSRIT Post, Bengaluru -560054
Bangalore
KARNATAKA 		 91-9845208163
91-80-23601983
drmaladharmalingam@gmail.com 
Dr Shaila Bhattacharya  Manipal Hospital Shushrut Diabetes & Endocrinology  Manipal Hospital,98, Opp to Leela Palace Road, HAL Airport Road, Kodhihalli, Bengaluru - 560017
Bangalore
KARNATAKA 		 91-9900655552
91-80-25207181
shailashamanur@gmail.com 
Dr Sunil Ambulkar  Meditrina Institute of Medical Sciences  278, Central Bazar Road, Ramdespath, Nagpur - 440012
Nagpur
MAHARASHTRA 		 91-9823037686
91-712-6669699
endodoc10@hotmail.com 
Dr Dinesh Kumar Pandey  MV Hospital and Research Centre  314/30, Mirza Mandi,Chowk, Lucknow – 226003
Lucknow
UTTAR PRADESH 		 91-9415156419
91-522-4016051
dr_dc_pandey@yahoo.com 
Dr Rama Walia  Post Graduate Institute of Medical Education and Research  Sector 12, Near Punjab University, Chandigarh -160012
Chandigarh
CHANDIGARH 		 91-9872997438
91-172-2744401
rumaahwaaliya@gmail.com 
Dr Archana Arya  Sir Ganga Ram Hospital  Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi - 110060
Central
DELHI 		 91-9999008525
91-11-25861002
adayal35@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 14  
Name of Committee  Approval Status 
Dr. Jivraj Mehta Smarak Health Foundation Institutional Ethics Committee  Approved 
Ethics Committee Apollo Specialty Hospital  Approved 
Ethics Committee – Institute of Child Health  Approved 
Ethics Committee Inamdar Multispecialty Hospital  Approved 
Ethics Committee Jehangir Clinical Development Centre Pvt. Ltd., Pune  Approved 
Ethics committee M.S Ramaiah medical College & Hospital  Approved 
Ethics Committee Meditrina Institute of Medical Sciences  Approved 
Ethics Committee of Manipal Hospital  Approved 
Ethics Committee Sir Ganga Ram Hospital  Approved 
Getwell Institutional Ethics Committee  Approved 
Institute of Ethics Committee All India Institute of Medical Sciences New Delhi  Approved 
Institutional Ethical Committee Care Hospital  Approved 
Institutional Ethics Committee M V Hospital & Research Center  Approved 
Institutional Ethics Committee PGMIER, Chandigarh  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
Patients  (1) ICD-10 Condition: E23||Hypofunction and other disorders of the pituitary gland,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Genotropin  Dose: 0.034 mg/kg/d; Frequency: Once in a day, 7 injections over a week; Route of administration : Subcutaneous; Total Duration of therapy: 365 Days 
Intervention  MOD-4023  Dose: 0.66 mg/kg/week; Frequency: One injection per week; Route of administration: Subcutaneous; Total Duration of therapy: 52 weeks 
 
Inclusion Criteria
Modification(s)  
Age From  3.00 Year(s)
Age To  12.00 Year(s)
Gender  Both 
Details  1. Pre-pubertal children aged equal or elder than 3 years, and not yet 11 years for girls (10 years
and 364 days) or not yet 12 years (11 years and 364 days) for boys, (on the
date of ICF signature), with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone deficiency.
2. Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak plasma GH level of equal or lesser then 10 ng/mL, determined by local or central
laboratory using a validated assay. Global study MM may accept prior local laboratory results, subject to pre-approval and if the tests were conducted as
recommended in the protocol Appendix B.
3. BA is not older than CA and should be lesser than 10 for girls and lesser than 11 for boys.
4. Without prior exposure to any recombinant hGH (r-hGH) therapy (naive patients).
5. Impaired Ht velocity defined as:
a. Annualized HV below the 25 percentile for CA (HV lesser than -0.7 SDS)
and gender according to the OPKO HV (Tanner, Prader and
Hermanussen) calculator, provided.
b. The interval between 2 Ht measurements should be at least 6 months, but should not exceed, 18 months prior to inclusion.
6. Baseline IGF-1 level of at least 1 standard deviation (SD) below the mean IGF-1 level standardized for age and sex (IGF-1 SDS equal or lesser than lesser than -1) according to the
central laboratory reference values. A single re-test will be allowed (subject
to discussion with MM) if all other criteria are met.
7. Normal calculated glomerular filtration rate (GFR) based on updated
bedside Schwartz formula for pediatric patients (calculation is
recommended below).
Creatine Clearance Rate (CrCL) (mL per min per 1.73 m 2) equals to 0.413 by Ht per serum
creatine (Scr)
Ht- in cm
Scr- in mg per dL.
8. Children with multiple hormonal deficiencies must be on stable replacement
therapies (no change in dose) for other hypothalamo-pituitary organ axes for
at least 3 months prior to ICF signing.
9. Normal 46XX karyotype for girls.
10. Willing and able to provide written informed consent of the parent or legal
guardian of the patient and written assent from pediatric patients (where
applicable based on age and country regulation).
Inclusion into the OLE:
11. Completion of the main study (12 months of treatment) with adequate
compliance.
12. Willing and able to provide written informed consent of the parent or legal
guardian of the patient and written assent from pediatric patients (where
applicable based on age and country regulation).
13. Agreement to refrain from sexual activity during the OLE i.e. observe
complete sexual abstinence as the only acceptable contraceptive measure
during the OLE (for pubertal and post-pubertal patients).


 
 
ExclusionCriteria 
Details  1. Children with prior history of leukemia, lymphoma, sarcoma or any other
forms of cancer.
2. History of radiation therapy or chemotherapy.
3. Malnourished children defined as BMI lesser than -2 SDS for age and sex.
4. Children with psychosocial dwarfism.
5. Children born small for gestational age (SGA – birth weight and/or birth
length lesser than -2 SDS for gestational age).
6. Presence of anti-hGH Ab at screening.
7. Any clinically significant (CS) abnormality likely to affect growth or the
ability to evaluate growth, such as, but not limited to, chronic diseases like
renal insufficiency, spinal cord irradiation, etc.
8. Types 1 and 2 diabetic patients who, in the opinion of the investigator, are
not receiving standard of care treatment, or are non-compliant with their
prescribed treatment or who are in poor metabolic control.(Criteria for
controlled diabetes are defined in Appendix F).
9. Chromosomal abnormalities including Turner syndrome, Laron
syndrome, Noonan syndrome, Prader-Willi syndrome, Russell-Silver
syndrome, SHOX mutations/deletions and skeletal dysplasias.
10. Concomitant administration of other treatments that may have an effect on
growth such as anabolic steroids, or sex steroids, with the exception of
Attention-Deficit-Hyperactivity Disorder (ADHD) drugs or hormone
replacement therapies (thyroxin, hydrocortisone, desmopressin
[DDAVP]).
11. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking
chronically a dose greater than 400 μg/day of inhaled budesonide or
equivalent as provided in Appendix J.
12. Major medical conditions and or presence of contraindication to r-hGH
treatment.
13. More than 1 closed epiphyses.
14. Known or suspected Human Immunodeficiency Virus (HIV)-positive
patient, or patient with advanced diseases such as Acquired
Immunodeficiency Syndrome (AIDS) or tuberculosis.
15. Drug, substance, or alcohol abuse.
16. Known hypersensitivity to the components of study medication.
17. Other causes of short stature such as celiac disease, uncontrolled primary
hypothyroidism and rickets.
18. The patient and or the parent or legal guardian are likely to be non-compliant
in respect to study conduct.
19. Participation in any other study of an investigational agent within 30 days
prior to ICF signature (including administration of investigational agent).
20. Study enrollment requirements have been met or the study has been closed
by the Sponsor prior to the completion of screening process.
Exclusion during the OLE:
21. Concomitant administration of other treatments that may have an effect on
growth such as anabolic steroids, or sex steroids (other than for hormonal
replacement), with the exception of ADHD drugs or hormone replacement
therapies (thyroxin, hydrocortisone, testosterone, estrogen and progesterone,
desmopressin [DDAVP])
22. Change in medical condition during the treatment period (such as, but not
limited to, development of a serious inter-current critical illness, a severe
adverse drug reaction, etc.)
23. Positive pregnancy test.
24. Unresolved drug related (MOD-4023 or Genotropin) SAE from the
treatment period as per MM judgement.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome
Modification(s)  
Outcome  TimePoints 
Annual HV in cm/year after 12 months of treatment.  After 12 months of treatment 
 
Secondary Outcome
Modification(s)  
Outcome  TimePoints 
Secondary efficacy endpoints (Auxology/Clinical):
1. Annualized HV after 6 months of treatment.
2. Change in Ht SDS at 6 and 12 months, compared to baseline.
3. Change in bone maturation (BM) at the end of 12 months, compared to
Baseline BA (calculated as BA/CA)
 		 1. After 6 months of treatment
2. At 6 and 12 months
3. At the end of 12 months 
Secondary endpoints (Biochemical)
1. Absolute IGF-1 and IGF-1 SDS levels on Day 4 (-1) after MOD-4023 dosing
across study visits.
2. IGFBP-3 levels and IGFBP-3 SDS on Day 4 (-1) after MOD-4023 dosing
across study visits.


 		 On Day 4 
OLE Endpoints:
Auxology/Clinical Endpoints
1. Annual HV in cm/year at completion of 12 months.
2. Change in height SDS at 12 months (compared to the previous
values).
3. Change in bone maturation (BM) at 12 months, (compared to Week
52 BA (calculated as BA/CA).
 		 12 Months 
OLE Endpoints:
Biochemical Endpoints
1. IGF-1 and IGF-1 SDS levels on day 4 (-1) after MOD-4023 dosing
across study visits.
2. IGFBP-3 levels and IGFBP-3 SDS on day 4 (-1) after MOD-4023
dosing across study visits.
 		 Day 4 
 
Target Sample Size   Total Sample Size="220"
Sample Size from India="32" 
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)  		 12/12/2017 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  05/12/2017 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial
Modification(s)  		 Years="3"
Months="0"
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
Modification(s)  		 Results of main study published 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

The study will consist of a 12 month, open-label, randomized, active controlled, parallel group study comparing the efficacy and safety of weekly MOD-4023 to daily growth hormone, Genotropin. After a screening period lasting up to 8 weeks, patients meeting the eligibility criteria, will be randomized 1:1 ratio to MOD-4023 (0.66 mg/kg/week) or growth hormone Genotropin (0.034 mg/kg/daily) for 7 injections over a week) for 12 months.

The total duration of patient participation in the study will be up to 15 months (12 months of treatment and up to 8 (+4) weeks of screening). The study will be conducted at approximately 150-180 sites in 30-40 countries worldwide.

 
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