Growth Hormone Deficiency MedDRA version: 12.1 Level: LLT Classification code 10056438 Term: Growth hormone deficiency
Conditions
Interventions
Product Name: n/a
Product Code: MOD-4023
Pharmaceutical Form: Solution for injection
Current Sponsor code: MOD-4023
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentr
Sponsors
ModigeneTech Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Genders Eligible for Study: Both Ages Eligible for Study: Males - 23 to 60 years, Females – 23 to 50 years. 1. GHDA subjects as defined in the Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II (2007). 2. Patients using hormonal replacement therapy(s) for deficiencies of other hypothalamo-pituitary axes must be on an optimized and stable treatment regimen (hormone levels within normal ranges on screening) for at least three months prior to screening: a. Temporary adjustment of glucocorticoid replacement therapy, as appropriate, is acceptable. b. Peripheral thyroid hormones (FT4, FT3) within the normal range. 3. Fertile females must agree to use appropriate contraceptive methods 4. Female patients must have a negative serum pregnancy test at inclusion. 5. GH replacement therapy for more than 6 months with registered GH product. 6. The IGF-I level at screening within -2 to +2 SDS of the age and sex normal ranges according to the central laboratory measurements.1 7. Body Mass Index (BMI, kg/m2) of 19.0 to 35.0 kg/m2, both inclusive 8. Confirmed to be negative for anti r-hGH antibodies at the time of screening. 9. Willing and able to provide written informed consent prior to performing any study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Females who are pregnant or breast-feeding 2. Evidence of growth of pituitary adenoma or other intracranial tumor within the last 12 months (confirmed by computer tomography (CT) or magnetic resonance imaging (MRI) scan (with contrast) within 3 months prior to study entry or at screening). 3. History of malignancy other than i) cranial irradiation (for cranial tumor or leukemia) causing GHD or ii) fully treated basal cell carcinoma 4. Signs of intracranial hypertension at screening 5. Heart insufficiency, NYHA class greater than 2 6. History of impaired glucose tolerance, insulin resistance or overt diabetes mellitus defined according to the American Diabetes Association (ADA) Criteria 7. Impaired liver function defined as elevation of liver enzymes >2 x upper limit of normal 8. Impaired kidney function defined as increased serum creatinine levels >1.5 x upper limit of normal 9. Active acromegaly in the last 18 months and less than 6 months of active r-hGH replacement therapy 10. Active Carpal tunnel syndrome 11. Prader-Willi syndrome 12. Active Cushing's syndrome within the last 12 months 13. Systemic corticosteroids other than in replacement doses within the 3 months before study entry (temporary adjustment of glucocorticoids, as appropriate, is acceptable) 14. Anabolic steroids other than gonadal steroid replacement therapy within 2 months before study entry 15. History of non-compliance with medications, uncooperativeness or drug abuse 16. Blood donation or any major blood loss >500 mL within the past 90 days prior to study entry 17. Patients who, based on the investigator’s judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Conditions may include cardiovascular, peripheral vascular, pulmonary, hepatic, renal, or neurological disease, as determined by medical history, physical examination, laboratory tests or ECG 18. Patients who participated in any investigational medicinal product (IMP) study within the last 2 months 19. History of positive serology to HBC, HBV and HIV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety, tolerability and Pharmacokinetics/ Pharmacodynamics (PK/PD) profile of three doses of MOD-4023 on a weekly regime and one dose on an EOW regime administered for a period of 4 weeks in Growth Hormone Deficient Adult (GHDA) patients who previously were on a stable r-hGH treatment.;Secondary Objective: 1. To select the optimal dose and dosing regimen of MOD-4023 for the subsequent phase III study on the basis of safety and PK/PD profile after 4 and 12 weeks of treatment. 2. To assess the long term safety and tolerability of MOD-4023 after 12 weeks dose administration. 3. To develop a population PK and PK/PD relationship model that may be utilized in later studies to predict PK concentrations for the PK/PD modeling and to simulate and explore various dosing regimen scenarios for further Modigenetech studies. ;Primary end point(s): The primary efficacy endpoint will be the mean time interval of IGF-I levels that lay within ±1.5 SDS after the last dose administration during stage I expressed in hours. Secondary efficacy endpoints: 1. Change of IGF-I levels over time in stage I and stage II expressed in absolute and SDS values 2. Change of IGF-PB3 over time in stage I and stage II expressed in absolute and SDS values 3. Time to achieve normalization of IGF-I during dose titration in stage II Safety assessments will consist of monitoring and recording: 1. Adverse events throughout the study 2. Immunogenicity of MOD 4023 (development of neutralizing antibodies) 3. Changes in vital signs and physical examination 4. Change in body weight 5. Fundoscopy for the occurrence of increased intracranial pressure 6. Change in the parameters of glucose metabolism: a. Fasting insulin level b. Fasting glucose levels c. HbA1c levels 7. Status of other hormonal axes: a. Thyroid hormones (free T4 and TSH) b. Cortisol levels 8. Laboratory parameters, including serum chemistry profile, liver enzymes, hematology, lipoproteins and urinalysis 9. Local tolera | — |
Countries
Czech Republic, Germany, Hungary, Slovakia, Slovenia
Outcome results
None listed