Safety and Efficacy Phase 2 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children

Study Overview
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Brief Summary
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This is a phase II, open label, active-controlled, randomized safety and dose finding study of different MOD-4023 dose levels compared to daily r-hGH therapy in pre-pubertal growth hormone deficient children.

Official Title
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Safety and Dose Finding Study of Different MOD-4023 Dose Levels Compared to Daily r-hGH Therapy in Pre-pubertal Growth Hormone Deficient Children

Conditions
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Pediatric Growth Hormone Deficiency

Intervention / Treatment
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* Drug: MOD-4023
* Drug: Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-pubertal child aged ≥ 3 yrs old and not above 10 years for girls or 11 years for boys with either isolated GHD, or GH insufficiency as part of multiple pituitary hormone deficiency. Confirmed diagnosis of GHD by two different GH provocation tests defined as a peak plasma GH level of ≤7 ng/ml, determined by central laboratory using a validated assay . Bone age (BA) is not older than chronological age and should be no greater than 9 years for girls and 10 years for boys. Without prior exposure to any r-hGH therapy. Normal birth size, birth weight and length for gestational age Impaired height and height velocity defined as: Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age (CA) and gender according to the standards from Prader et. al, 1989 , (HT SDS ≤ -2.0). Annualized height velocity (HV) below the 25th percentile for CA (HV <-0.7 SDS) and gender according to the standards of Prader et al (1989). The interval between two height measurements should be at least 6 months before inclusion. BMI must be within ±2 SD of mean BMI for the chronological age and sex according to the 2000 CDC standards. Baseline IGF-I level of at least 1 SD below the mean IGF-I level standardized for age and sex (IGF-I SDS ≤ -1.0) according to the central laboratory reference values; 12. Written informed consent of the parent or legal guardian of the patient and assent of the patient (if the patient can read). Exclusion Criteria: Children with past or present intracranial tumor growth as confirmed by an MRI scan (with contrast). History of radiation therapy or chemotherapy. Malnourished children defined as: Serum albumin below the lower limit of normal (LLN) according to the reference ranges of central laboratory; Serum iron below the lower limit of normal (LLN) according to the reference ranges of central laboratory; BMI < -2 SD for age and sex; Children with psychosocial dwarfism. Children born small for gestational age (SGA - birth weight and/or birth length < -2 SD for gestational age). Presence of anti-hGH antibodies at screening. 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. Patients with diabetes mellitus. Patients with impaired fasting sugar (based on WHO; fasting blood sugar >110 mg/dl or 6.1 mmol/l) after repeated blood analysis. Chromosomal abnormalities and medical syndromes (Turner's syndrome, Laron syndrome, Noonan syndrome, Prader-Willi Syndrome, Russell-Silver Syndrome, SHOX mutations/deletions and skeletal dysplasias), with the exception of septo-optic dysplasia. Closed epiphyses. 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)) 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. Major medical conditions and/or presence of contraindication to r-hGH treatment. Known or suspected HIV-positive patient, or patient with advanced diseases such as AIDS or tuberculosis. Drug, substance, or alcohol abuse. Known hypersensitivity to the components of study medication. Other causes of short stature such as coeliac disease, hypothyroidism and rickets. The patient and/or the parent/legal guardian are likely to be non-compliant in respect to study conduct. Participation in any other trial of an investigational agent within 30 days prior to Screening.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOD-4023 low dose<br>Once weekly subcutaneous injection of long acting r-hGH (MOD-4023) | Drug: MOD-4023<br>* Once weekly subcutaneous injection<br>|
| Experimental: MOD-4023 middle dose<br>Once weekly subcutaneous injection of long acting r-hGH (MOD-4023) | Drug: MOD-4023<br>* Once weekly subcutaneous injection<br>|
| Experimental: MOD-4023 high dose<br>Once weekly subcutaneous injection of long acting r-hGH (MOD-4023) | Drug: MOD-4023<br>* Once weekly subcutaneous injection<br>|
| Active Comparator: Genotropin<br>Once daily subcutaneous injection of Somatropin (r-hGH; Genotropin) | Drug: Somatropin<br>* Once daily subcutaneous injection of Genotropin<br>* Other names: Genotropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Height Velocity | Annual Height Velocity in cm/year measured after 12 months of treatment | 12 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity at 6 Months | Annualized Height Velocity in cm/year measured after 6 months of treatment | After 6 months of treatment | 
| Change in Height Standard Deviation Score (SDS) | Change in height standard deviation score from baseline (compared to normal population of same age group and sex). Height SDS was calculated as height minus reference mean height divided by SD of the reference mean height | After 6 and 12 months of treatment | 
| Change in IGF-1 Standard Deviation Score | Change in IGF-1 standard deviation score from reference population mean of same age group and sex (WHO source). IGF-1 SDS was calculated as IGF-1 result minus reference mean IGF-1 result divided by SD of the reference mean IGF-1 value. | Once monthly on day 4 after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GHD, r-hGH, Long-acting