Growth hormone deficiency in pre-pubertal children MedDRA version: 20.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Somatrogon
CAS Number: 1663481-09-1
Current Sponsor code: MOD-4023
Concentration unit: mg/ml m
Sponsors
OPKO Biologics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion into the main study: 1. Pre-pubertal children aged =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 =10 ng/mL, determined by local or central laboratory using a validated assaya. 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion during the main study: 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 < -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 <-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’s 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/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 LT-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/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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that weekly MOD-4023 administration is non-inferior to daily Genotropin administration.;Secondary Objective: To evaluate the safety and tolerability of weekly MOD-4023 administration. To demonstrate long term (LT) safety and efficacy of MOD-4023 in an open-label extension (OLE).;Primary end point(s): Annual Height Velocity (HV) in cm/year;Timepoint(s) of evaluation of this end point: Main Study: Baseline and after 12 months of treatment LT-OLE: At each 12-month interval | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main Study: Secondary efficacy endpoints (Auxology/Clinical): • Annualized HV after 6 months of treatment. • Change in Ht SDS at 6 and 12 months, compared to baseline. • Change in bone maturation (BM) at the end of 12 months, compared to Baseline BAa (calculated as BA/CA). Secondary endpoints (Biochemical): • Absolute IGF-1 and IGF-1 SDS levels on Day 4 (-1) after MOD-4023 dosing across study visits. • IGFBP-3 levels and IGFBP-3 SDS on Day 4 (-1) after MOD-4023 dosing across study visits. LT-OLE Endpoints: Safety Endpoints • Incidence of AEs and SAEs; • Incidence of anti-MOD-4023 Ab formation (including characterization of the Ab and neutralizing properties); • Local injection site reaction assessment; • Parameters of glucose metabolism: blood fasting glucose, fasting insulin level, HbA1c; • Thyroid (endocrinology) status; • Lipid profile; • All other safety hematology, biochemical parameters and urinalysis; • Physical examination; • Fundoscopy results - if performed (normal/abnormal); • Vital signs; • ECG. Auxology/Clinical Endpoints • Annual HV in cm/year at each 12-month interval. • Change in height SDS every 12 months (compared to the previous values). • Change in bone maturation (BM) every 12 months, (compared to Week 52 BA (calculated as BA/CA) at completion of LT-OLE year 1 and to previous values from LT-OLE year 2 onwards). Biochemical Endpoints • IGF-1 and IGF-1 SDS levels on day 4 (-1) after MOD-4023 dosing across study visits. • IGFBP-3 levels and IGFBP-3 SDS on day 4 (-1) after MOD-4023 dosing across study visits.;Timepoint(s) of evaluation of this end point: as above | — |
Countries
Argentina, Australia, Belarus, Bulgaria, Canada, Colombia, France, Georgia, Germany, Greece, India, Israel, Italy, Mexico, New Zealand, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactDirector of Clinical Affairs
OPKO Biologics Ltd.
Outcome results
None listed