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
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      This is a 12-month, open-label, randomized, active controlled, parallel group study comparing
      the efficacy and safety of weekly MOD-4023 to daily recombinant human growth hormone (r-hGH),
      Genotropin ®. Both drugs will be injected subcutaneously (SC) using a pen device.

      After a 4 week Screening period, patients meeting all the entry criteria and none of the
      exclusion criteria, will be eligible to participate in the study.

      Eligible patients will be randomized in a 1:1 ratio, to receive either:

      • MOD-4023 (investigational treatment): weekly MOD-4023 SC injections for 12 months;
      initially over the first 6 weeks, MOD-4023 will be administered in 3 stepwise escalating
      doses (0.25 mg/kg/week, 0.48 mg/kg/week and 0.66 mg/kg/week), each for two weeks
      sequentially. For the remaining 46 weeks, patients will continue to receive MOD-4023 at a
      dose of 0.66 mg/kg/week.

      Or

      • Genotropin® (reference treatment): daily Genotropin® (0.025 mg/kg/day which is equivalent
      to 0.175 mg/kg/week, divided equally into 7 daily injections over a week) SC injection for 12
      months.

      After the 6-week PK/PD sampling period, the dose of MOD-4023 and Genotropin® will be adjusted
      every 3 months based on a patient's body weight. Doses may be decreased for safety reasons
      according to the pre-defined dose-adjustment criteria (which will be based on the severity of
      adverse events (AEs) or repeated, elevated levels of IGF-1 Standard Deviation Score (SDS)).

      The key safety data will be reviewed by an independent and external Data and Safety
      Monitoring Board (DSMB). DSMB review will also include a review of the number or percentage
      of patients requiring dose reductions due to AEs. Following the completion of the12-month
      treatment period, eligible patients will be consented to enroll into an open-label long term
      extension (LTE) period, and an amendment to this study protocol will be submitted prior to
      the first patient completes the 12 months treatment period. Eligible Genotropin®-treated
      patients will be switched to a MOD-4023 dose of 0.66 mg/kg/week in the LTE. The LTE is
      planned to continue until MOD-4023 marketing registration in Japan.
    

Intervention name(s): MOD-4023; Genotropin
Intervention type(s): Drug; Drug
Intervention description(s): 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).
Other intervention name(s): Somatrogon
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Other