Growth Hormone Deficiency (GHD)
Conditions
Keywords
Growth hormone deficiency (GHD), r-hGH, Long-acting
Brief summary
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.
Interventions
DRUGMOD-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).
Sponsors
OPKO Health, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 11 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Height Velocity | 8 years | 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). |
| Delta Height SDS Every 12 Months | 8 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of IGF-1 SDS | 8 years | 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%. |
Countries
Belarus, Greece, Hungary, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
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). | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Due to war activity | 1 |
| Overall Study | Final height achieved | 5 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 15 |
Baseline characteristics
| Characteristic | MOD-4023 |
|---|---|
| Age, Continuous | 7.67 years STANDARD_DEVIATION 2.122 |
| Age, Customized ≥ 10 and ≤ 14 years | 10 Participants |
| Age, Customized ≥ 7 and < 10 years | 13 Participants |
| Age, Customized < 7 years | 25 Participants |
| Pubertal Status Tanner II (Early puberty) | 1 Participants |
| Pubertal Status Tanner III (Mid puberty) | 0 Participants |
| Pubertal Status Tanner I (Prepubertal) | 47 Participants |
| Pubertal Status Tanner IV (Late puberty) | 0 Participants |
| Pubertal Status Tanner V (Post pubertal) | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 45 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 48 |
| other Total, other adverse events | 42 / 48 |
| serious Total, serious adverse events | 4 / 48 |
Outcome results
Primary
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).
Time frame: 8 years
Population: Full analysis population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOD-4023 | Annualized Height Velocity | PEN Year 1 | 6.98 cm/year | Standard Deviation 1.89 |
| MOD-4023 | Annualized Height Velocity | OLE Year 1 | 7.99 cm/year | Standard Deviation 1.54 |
| MOD-4023 | Annualized Height Velocity | OLE Year 2 | 7.46 cm/year | Standard Deviation 1.35 |
| MOD-4023 | Annualized Height Velocity | OLE Year 3 | 7.12 cm/year | Standard Deviation 1.66 |
| MOD-4023 | Annualized Height Velocity | OLE Year 4 | 4.63 cm/year | — |
| MOD-4023 | Annualized Height Velocity | PEN Year 2 | 6.37 cm/year | Standard Deviation 2.12 |
| MOD-4023 | Annualized Height Velocity | PEN Year 3 | 5.31 cm/year | Standard Deviation 1.68 |
| MOD-4023 | Annualized Height Velocity | PEN Year 4 | 6.05 cm/year | Standard Deviation 1.74 |
| MOD-4023 | Annualized Height Velocity | PEN Year 5 | 6.31 cm/year | Standard Deviation 0.41 |
Primary
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.
Time frame: 8 years
Population: Full analysis population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOD-4023 | Delta Height SDS Every 12 Months | PEN Year 5 | 0.07 Z-score | Standard Deviation 0.13 |
| MOD-4023 | Delta Height SDS Every 12 Months | OLE Year 3 | 0.34 Z-score | Standard Deviation 0.28 |
| MOD-4023 | Delta Height SDS Every 12 Months | OLE Year 1 | 0.57 Z-score | Standard Deviation 0.34 |
| MOD-4023 | Delta Height SDS Every 12 Months | OLE Year 2 | 0.40 Z-score | Standard Deviation 0.28 |
| MOD-4023 | Delta Height SDS Every 12 Months | OLE Year 4 | 0.09 Z-score | — |
| MOD-4023 | Delta Height SDS Every 12 Months | PEN Year 1 | 0.27 Z-score | Standard Deviation 0.25 |
| MOD-4023 | Delta Height SDS Every 12 Months | PEN Year 2 | 0.21 Z-score | Standard Deviation 0.29 |
| MOD-4023 | Delta Height SDS Every 12 Months | PEN Year 3 | 0.10 Z-score | Standard Deviation 0.21 |
| MOD-4023 | Delta Height SDS Every 12 Months | PEN Year 4 | 0.18 Z-score | Standard Deviation 0.34 |
Secondary
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%.
Time frame: 8 years
Population: Full analysis population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOD-4023 | Summary of IGF-1 SDS | OLE Year 1 | 0.64 Z-score | Standard Deviation 0.96 |
| MOD-4023 | Summary of IGF-1 SDS | OLE Year 2 | 0.65 Z-score | Standard Deviation 1.08 |
| MOD-4023 | Summary of IGF-1 SDS | OLE Year 3 | 1.05 Z-score | Standard Deviation 0.82 |
| MOD-4023 | Summary of IGF-1 SDS | OLE Year 4 | 0.29 Z-score | — |
| MOD-4023 | Summary of IGF-1 SDS | PEN Year 1 | 1.29 Z-score | Standard Deviation 0.81 |
| MOD-4023 | Summary of IGF-1 SDS | PEN Year 2 | 0.96 Z-score | Standard Deviation 1.15 |
| MOD-4023 | Summary of IGF-1 SDS | PEN Year 3 | 0.86 Z-score | Standard Deviation 0.89 |
| MOD-4023 | Summary of IGF-1 SDS | PEN Year 4 | 1.00 Z-score | Standard Deviation 0.68 |
| MOD-4023 | Summary of IGF-1 SDS | PEN Year 5 | 1.45 Z-score | Standard Deviation 0.33 |