Safety and Efficacy Study of MOD-4023 to Treat Children With Growth Hormone Deficiency
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03874013|
Recruitment Status : Completed
First Posted : March 14, 2019
Last Update Posted : March 27, 2020
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.
• To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of three different doses of MOD-4023 in Japanese pre-pubertal children with GHD.
|Condition or disease||Intervention/treatment||Phase|
|Growth Hormone Deficiency||Drug: MOD-4023 Drug: Genotropin||Phase 3|
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.
• 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Phase 3, Open-Label, Randomized, Multicenter, 12-month, Efficacy and Safety Study of Weekly MOD-4023 Compared to Daily Genotropin® Therapy in Japanese Pre-pubertal Children With Growth Hormone Deficiency|
|Actual Study Start Date :||December 7, 2017|
|Actual Primary Completion Date :||March 6, 2020|
|Actual Study Completion Date :||March 6, 2020|
Experimental: MOD-4023 Treatment Arm
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.
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.
Other Name: Somatrogon
Active Comparator: Genotropin Treatment Arm
Genotropin® (reference treatment): daily Genotropin® (0.025 mg/kg/day).
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 (GenotropinÒ) 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).
- Annual Height Velocity (HV) after 12 months [ Time Frame: 12 months ]Annual Height Velocity in cm/year after 12 months of treatment.
- Height Velocity at 6 months [ Time Frame: 6 months ]Annualized height velocity (cm/year) for the MOD-4023 and the daily hGH treatment groups
- Change in height standard deviation score (SDS) compared to baseline [ Time Frame: 12 months ]Change in height standard deviation score (SDS) for the MOD-4023 and the daily hGH treatment groups
- Change in bone maturation (BM) [ Time Frame: 12 months ]Change in bone maturation (bone age / chronological age) with the method of TW2 using a central bone age reader.
- Biochemical [ Time Frame: 12 months ]
- MOD-4023, IGF-1 and IGF-BP3 levels on each dose level at escalating doses of 0.25 to 0.66 mg/kg/week.
- Absolute IGF-1 serum levels on day 4(-1) after MOD-4023 dosing across study visits (window only applies to visits 6 to 9)
- IGF-1 SDS on day 4(-1) after MOD-4023 dosing across study visits (window only applies to visits 6 to 9)
- IGF-BP3 serum levels and IGF-BP3 SDS during the PK/PD period according to the sub-block schedule
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03874013
|Principal Investigator:||Reiko Horikawa, M.D, Ph. D.||National Center for Child Health and Development|