Safety and Efficacy Study of MOD-4023 to Treat Children With Growth Hormone Deficiency
Condition: Growth Hormone Deficiency
MeSH terms: Dwarfism, Pituitary; Endocrine System Diseases
Intervention: MOD-4023; Genotropin
Intervention description: MOD-4023 is a long-acting modified recombinant human growth hormone (r-hGH) which utilizes C-terminal peptide (CTP) technology. It will be provided as a solution for injection containing 20 or 50 mg/mL MOD-4023 in a multi-dose disposable pre-filled PEN.
MOD-4023 will be administered as a SC injection once weekly, using a delivery device.; Genotropin® is dispensed in a 2-chamber cartridge. The front compartment contains recombinant somatropin, glycine, mannitol, sodium dihydrogen phosphate anhydrous and disodium phosphate anhydrous. The rear compartment contains m-Cresol and mannitol in water for injections.
A delivery device (Genotropin®) will be used for daily (evening/bedtime) SC administration of Genotropin® into the region of the upper arms, buttocks, thighs or abdomen (8 locations). Injection sites should be rotated.
Dose regimen for Genotropin®: 0.025 mg/kg/day (or 0.175 mg/kg/w divided equally to 7 injections over a week).
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 3 Years
Maximum age: 11 Years
Healthy volunteers: No

Summary:

      Treatment of children with growth failure due to growth hormone deficiency (GHD).

      Primary • To evaluate the efficacy and safety of weekly MOD-4023 administration compared to
      daily Genotropin® administration in Japanese pre-pubertal children with GHD.

      Secondary

      • To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of three different
      doses of MOD-4023 in Japanese pre-pubertal children with GHD.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pre-pubertal child aged ≥ 3 years old, and not yet 10 years for girls (9 years and 364
             days) or not yet 11 years for boys (10 years and 364 days), 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 2 different types of GH provocation tests (standardized
             on growth foundation data): defined as a peak serum GH level of ≤ 6.0 ng/mL or ≤ 16
             ng/mL when conducting GHRP-2 provocation test.

             Prior local laboratory results will be accepted subject to pre-approval by the study
             medical monitor and if the tests were conducted as specified in the protocol.

          3. Bone age (BA) is not older than chronological age and should be less than 10 for girls
             and less than 11 for boys.

          4. Without prior exposure to any r-hGH therapy.

          5. Height SD score ≤ -2.0 at screening

          6. Impaired height velocity defined as:

               -  Annualized height velocity (HV) below the 25th percentile for CA (HV < -0.7 SDS)
                  and gender according to the local primary care provider standard.

               -  The interval between two height measurements should be at least 6 months, but
                  should not exceed 18 months prior to inclusion.

          7. BMI must be within ±2 SDS of mean BMI for the chronological age and sex.

          8. Baseline IGF-1 level of at least 1 SDS below the mean IGF-1 level standardized for age
             and sex (IGF-1 SDS ≤ -1) according to the central laboratory reference values. A
             single re-test will be allowed (subject to discussion with the study medical monitor)
             if all other criteria are met.

          9. Normal creatinine levels according to common practice reference ranges per age.

         10. Children with multiple hormonal deficiencies must be on stable replacement therapies
             (no change in dose) for other hypothalamo-pituitary organ axes for at least 3 months
             prior to ICF signing

         11. Normal 46 XX karyotype for girls.

         12. Willing and able to provide written informed consent of the parent or legal guardian
             of the patient and written assent from pediatric patients (when applicable based on
             age and Japan regulation).

        Exclusion Criteria:

          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 suspected psychosocial dwarfism by the discretion of the investigator

          5. Children born small for gestational age (SGA - birth weight and/or birth length < -2
             SDS 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. Children with diabetes mellitus

          9. Chromosomal abnormalities including Turner's syndrome, Laron syndrome, Noonan
             syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX (short stature
             homeobox) mutations/deletions and skeletal dysplasia's, with the exception of
             septo-optic dysplasia.

         10. Concomitant administration of other treatments that may have an effect on growth such
             as anabolic steroids, sex steroids, with the exception of 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/d of inhaled budesonide or equivalent as
             provided in Appendix J.

         12. Major medical conditions and/or presence of contraindication to r-hGH treatment.

         13. Known or suspected HIV-positive patient, or patient with advanced diseases such as
             AIDS or tuberculosis.

         14. Drug substance or alcohol abuse.

         15. Known hypersensitivity to the components of study medication.

         16. Other causes of short stature such as celiac disease, uncontrolled primary
             hypothyroidism and rickets.

         17. The patient and/or the parent/legal guardian are likely to be non-compliant in respect
             to study conduct.

         18. Participation in any other clinical trial within 30 days prior to screening and
             throughout the entire study period (including administration of investigational
             agent).