Long Term Follow up Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children

Safety and Dose Finding Study of Different MOD-4023 Dose Levels Compared to Daily R-human Growth Hormone (hGH) Therapy in Pre-pubertal Growth Hormone Deficient Children

Protocol CP-4-004-OLE (Open Label Extension) is designed as a long-term, open-label extension using single patient use, multi-dose, disposable pre-filled pen.

Study Overview

• Status: Completed
• Conditions: Growth Hormone Deficiency (GHD)
• Intervention / Treatment: Drug: MOD-4023

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belarus
  • Minsk, Belarus
    • 2DKB
• Greece
  • Athens, Greece
    • Children's Hospital "P. A. Kyriakou"
• Hungary
  • Budapest, Hungary
    • Buda Children's Hospital
• Russian Federation
  • Moscow, Russian Federation
    • Endocrinology Scientific Centre, Institute of Child Endocrinology
  • Moscow, Russian Federation
    • Russian Medical Academy of Postgraduate Education
  • Saint Petersburg, Russian Federation
    • SPGPMA
  • Samara, Russian Federation
    • SamGMU
  • Ufa, Russian Federation
    • SBEIHPE
• Ukraine
  • Donetsk, Ukraine
    • Donetsk Regional Children Clinical Hospital
  • Kiev, Ukraine
    • Institute of Endocrinology
  • Kiev, Ukraine
    • Ukrainian Scientific Center of Endocrine Surgery Moh of Ukraine
  • Odessa, Ukraine
    • Odessa Regional Children'S Clinical Hospital
• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients who completed the first year of treatment in the main study are allowed to enter the (Long Term) Open Label Extension (OLE) study.

Exclusion Criteria:

1. Children with past or present intracranial tumor growth as confirmed by an MRI scan (with contrast).
2. History of radiation therapy or chemotherapy.

3. Malnourished children defined as:

   1. Serum albumin below the lower limit of normal (LLN) according to the reference ranges of central laboratory;
   2. Serum iron below the lower limit of normal (LLN) according to the reference ranges of central laboratory;
   3. BMI < -2 Standard Deviation for age and sex;
4. Children with psychosocial dwarfism.
5. Children born small for gestational age (SGA - birth weight and/or birth length < -2 SD for gestational age).
6. Presence of anti-hGH antibodies at screening.
7. Any clinically significant 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. Patients with diabetes mellitus.
9. Patients with impaired fasting sugar (based on WHO; fasting blood sugar >110 mg/dl or 6.1 mmol/l) after repeated blood analysis.
10. Chromosomal abnormalities and medical "syndromes" (Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi Syndrome, Russell-Silver Syndrome, short stature homeobox-containing gene (SHOX) mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia.
11. Closed epiphyses.
12. Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids and methylphenidate for attention deficit hyperactivity disorder (ADHD), with the exception of hormone replacement therapies (thyroxine, hydrocortisone, desmopressin (DDAVP))
13. Children requiring glucocorticoid therapy (e.g. asthma) who are taking a dose of greater than 400 µg/d of inhaled budesonide or equivalents for longer than 1 month during a calendar year.
14. Major medical conditions and/or presence of contraindication to r-hGH treatment.
15. Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis.
16. Drug, substance, or alcohol abuse.
17. Known hypersensitivity to the components of study medication.
18. Other causes of short stature such as coeliac disease, hypothyroidism and rickets.
19. The patient and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct.
20. Participation in any other trial of an investigational agent within 30 days prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MOD-4023; Once weekly injection of long acting r-hGH (MOD-4023) provided as a solution for injection containing 20 or 50 mg/mL MOD-4023 in a single patient use, multi-dose, disposable pre-filled pen (PEN).	Drug: MOD-4023; Once weekly injection of long acting r-hGH (MOD-4023) provided as a solution for injection containing 20 or 50 mg/mL MOD-4023 in a single patient use, multi-dose, disposable pre-filled pen (PEN).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Height Velocity	A summary of the annualized HV at the end of each year for Periods III/IV (OLE Years 1 - 4) and V (PEN Years 1 - 5).	8 years
Delta Height SDS Every 12 Months	A summary of annual change in height SDS at the end of each year for Periods III/IV (OLE Years 1 - 4) and V (PEN Years 1 - 5). Height SDS (Standard Deviation Score) reflects how an individual's height compares to the average for their age and sex, calculated using Growth Analyzer and based on Switzerland 1989 (Prader) reference. A z-score of 0 indicates a height equal to the population mean, while positive scores indicate above-average heights and negative scores reflect below-average heights.	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of IGF-1 SDS	A summary of IGF-I SDS at the end of each year for Periods III/IV (OLE Years 1 - 4) and V (PEN Years 1 - 5). IGF-1 SDS (Standard Deviation Score) reflects how an individual's IGF-1 level compares to the average for their age and sex, based on reference values from Bidlingmaier et al. (2014, The Journal of Clinical Endocrinology & Metabolism, 99(5):1712-1721). A z-score of 0 indicates a level equal to the population mean, while positive scores indicate above-average levels and negative scores reflect below-average levels. An IGF-1 SDS below -2 suggests deficiency, whereas a score above +2 is considered elevated. In the study, when IGF-1 SDS exceeded +2, a confirmatory test was performed, and if elevation was confirmed, the dose was reduced by 15%.	8 years

Other Outcome Measures

Outcome Measure	Time Frame
IGFBP-3 levels on day 3 or 4 after MOD-4023 dosing	8 years

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.
• Investigators: Principal Investigator: Zvi Zadik, MD, Kaplan Medical Center, Israel

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: July 12, 2015
• First Submitted That Met QC Criteria: July 14, 2015
• First Posted (Estimated): July 16, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Growth hormone deficiency (GHD); r-hGH; Long-acting
• Other Study ID Numbers: CP-4-004-OLE; 2011-004553-60 (EudraCT Number)