A Non-inferiority Phase 2 Study to Evaluate the Safety and Efficacy of PEG-rhGH in the Treatment of AGHD

Study Overview
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Brief Summary
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This study aims to explore the optimal dose of PEG-rhGH injection in the treatment of AGHD, preliminarily evaluate its safety and efficacy, to provide scientific and reliable evidence for the medication dosage in Phase 2 clinical study.

Official Title
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A Non-inferiority Phase 2 Study to Evaluate the Safety and Efficacy of PEG-rhGH in the Treatment of Adult Growth Hormone Deficiency (AGHD)

Conditions
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Adult Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Somatropin Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Before the treatment, the subject should be diagnosed as AGHD based on medical history, clinical symptoms, vital signs, insulin tolerance test and imagological examinations. The subject is diagnosed as GHD during childhood and remains as GHD in adulthood, and the linear growth has completed: bone age (BA) ≥18 years old; or the AGHD patient who experiences paroxysm after 18 years old: such as patients who have experienced pituitary surgeries (2 years after pituitary adenoma surgery, 5 years after craniopharyngioma surgery and 12 months after other pituitary surgeries), traumatic brain injury (TBI), Sheehan syndrome, and etc.. The plasma GH concentration peak is <5ng/ml in insulin tolerance test (ITT) (it's unnecessary to conduct ITT in the following conditions: anterior pituitary dysfunction, pituitary hormone deficiency (more than 3 hormones) and serum IGF-1 level below lower limit of normal value: i.e. -2 SD). Age: 18-60 years old. Patients with no history of GH treatment for more than one year. Body mass index (BMI): 18.5 kg/m2≤BMI≤30kg/m2. When there is other hormones deficiency (such as glucocorticoids, thyroid hormones and sex steroids), the subject should have received other hormone replacement therapies and the therapeutic dose shall be stable within 3 months before the enrolment. The subject agrees to cooperate and complete the concerted trial procedures such as follow-ups, treatment plan and laboratory examinations, and sign the written informed consent. Exclusion Criteria: Patients with serious heart diseases, including NYHA III or above, serious arrhythmia, unstable angina pectoris or myocardial infarction within the latest 6 months. Patients with a history of ischemic cerebrovascular disease, febrile convulsion and epilepsy seizures. Patients with carpal tunnel syndrome. Patients with poor hypertension control (systolic pressure>140mmHg or diastolic pressure >90mmHg under treatment). Patients with previous or present history of malignant tumor: two or more direct relatives within three generations have previous or present history of tumor. Patients undergoing anti-depressive therapy, immunosuppressive therapy, chemotherapy and radiotherapy (or with a history of radiotherapy). Patients who have ever taken antiobesity drug within the latest 3 months. Patients with serious infection. Patients with consciousness disorders and mental diseases. Subjects with impaired glucose regulation (IGR) (impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) ) or diabetes; patients with a family history of diabetes (direct relatives). Subjects with abnormal liver and kidney functions (ALT > 2 times of upper limit of normal value; eGFR calculated by MDRD formula <60). Subjects positive for anti-HBc, HBsAg or HBeAg in Hepatitis B virus tests. Subjects with highly allergic constitution or allergy to proteins or investigational productorits excipient in this study. Subjects who took part in other clinical trials within 3 months. Patients with other mental or physical deficiencies that influence the evaluation of investigational product. Pregnant or lactating women; females planning to get pregnant within one year. Subjects whose tumor markers exceed the upper limit of normal range and the re-examination result is still high. Other conditions which is unsuitable for the study in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-rhGH-1<br>Pegylated recombinant human growth hormone injection, 12IU/2.0mg/1.0ml/bottle. The first stage, 1-2mg/2-4mg, subcutaneous injection,weekly, 26 weeks. | Drug: Somatropin Injection<br>* Recombinant human growth hormone injection, 15IU/5mg/3ml/bottle. The first stage , 0.17mg/d(0.5IU/d), subcutaneous injection ,daily, 26weeks. The second stage(extension period study), 0.17mg/d(0.5IU/d), maximum ≤0.68mg/d (2IU/w),52 weeks.<br>* Other names: Recombinant human growth hormone injection;|
| Experimental: PEG-rhGH-2<br>Pegylated recombinant human growth hormone injection, 12IU/2.0mg/1.0ml/bottle. The second stage (extension period study), maximum ≤4mg/w (24IU/w), 52 weeks. | Drug: Somatropin Injection<br>* Recombinant human growth hormone injection, 15IU/5mg/3ml/bottle. The first stage , 0.17mg/d(0.5IU/d), subcutaneous injection ,daily, 26weeks. The second stage(extension period study), 0.17mg/d(0.5IU/d), maximum ≤0.68mg/d (2IU/w),52 weeks.<br>* Other names: Recombinant human growth hormone injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat mass change | Change from baseline in fat mass (torso) (FM): FM at the end of treatment minus the baseline value | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lean body mass change | Change from baseline in lean body mass (LBM): LBM at the end of treatment minus the baseline value | 52 weeks | 
| Blood lipid change | Change from baseline in blood lipid: blood lipid at the end of treatment minus the baseline value | 52 weeks | 
| Waist circumference change | Change from baseline in waist circumference: waist circumference at the end of treatment minus the baseline value | 52 weeks | 
| Percentage of body fat change | Change from baseline in the percentage of body fat: TBF at the end of treatment minus the baseline value | 52 weeks | 
| Cardiac function change | Change from baseline in cardiac function: ejection fraction at the end of treatment minus the baseline value | 52 weeks | 
| Cardiac structure change | Change from baseline in cardiac structure: left ventricular mass at the end of treatment minus the baselines value | 52 weeks | 
| IGF-1 change | Changes from baseline in IGF-1: IGF-1 SDS at the end of treatment minus the baseline value | 52 weeks | 
| Grip change | Changes from baseline in grip: grip at the end of treatment minus the baseline value, the method of assessment is measurement. | 52 weeks | 
| Quality of life change | Changes from baseline in quality of life (QOL): changes in QOL scores before and after treatment | 52 weeks | 
| Waist-hip ratio change | Changes from baseline in waist-hip ratio: changes of waist-hip ratio before and after treatment | 52 weeks | 
| Cardiac structure change | Change from baseline in cardiac structure: carotid intima media thickness at the end of treatment minus the baselines value | 52 weeks |