Safety and Efficacy Phase 2 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient Children
Condition: Pediatric Growth Hormone Deficiency
Intervention: MOD-4023; Somatropin
Intervention description: Once weekly subcutaneous injection; Once daily subcutaneous injection of Genotropin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 3 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: GHD; r-hGH; Long-acting

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. 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
             .

          3. Bone age (BA) is not older than chronological age and should be no greater than 9
             years for girls and 10 years for boys.

          4. Without prior exposure to any r-hGH therapy.

          5. Normal birth size, birth weight and length for gestational age

          6. Impaired height and height velocity defined as:

               1. 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).

               2. 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.

          7. BMI must be within ±2 SD of mean BMI for the chronological age and sex according to
             the 2000 CDC standards.

          8. 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;

          9. 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:

          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 SD 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, 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.