Clinical trial NCT03104010: A Non-inferiority Phase 2 Study to Evaluate the Safety and Efficacy of PEG-rhGH in the Treatment of AGHD
Official title: A Non-inferiority Phase 2 Study to Evaluate the Safety and Efficacy of PEG-rhGH in the Treatment of Adult Growth Hormone Deficiency (AGHD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Adult Growth Hormone Deficiency
Lead sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking Union Medical College Hospital
name: Peking University First Hospital
name: Hebei General Hospital
name: The Second Hospital of Hebei Medical University
name: Qilu Hospital of Shandong University
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: The First Affiliated Hospital of Soochow University
name: First Affiliated Hospital of Chongqing Medical University
name: Chongqing Three Gorges Central Hospital
name: West China Hospital
First posted: 2017-04-07
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Fat mass change
timeFrame: 52 weeks
Secondary outcomes:
measure: Lean body mass change
timeFrame: 52 weeks
measure: Blood lipid change
timeFrame: 52 weeks
measure: Waist circumference change
timeFrame: 52 weeks
measure: Percentage of body fat change
timeFrame: 52 weeks
measure: Cardiac function change
timeFrame: 52 weeks
measure: Cardiac structure change
timeFrame: 52 weeks
measure: IGF-1 change
timeFrame: 52 weeks
measure: Grip change
timeFrame: 52 weeks
measure: Quality of life change
timeFrame: 52 weeks
measure: Waist-hip ratio change
timeFrame: 52 weeks
measure: Cardiac structure change
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Heibei General Hospital
state: Hebei
city: Suzhou
country: China
facility: The Affiliated hospital of soochow University
state: Jiangsu
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University school of medicine
state: Zhejiang
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
Study officials:
affiliation: Peking Union Medical College Hospital
name: Hui Pan, Doctor
role: PRINCIPAL_INVESTIGATOR
References: