Adult Growth Hormone Deficiency (AGHD)
Conditions
Keywords
adult growth hormone deficiency, GS3-007a dry suspension
Brief summary
The GS3-007a Growth Hormone Stimulation Test (GHST) will be compared with the Insulin Tolerance Test (ITT) in an open-label, randomized, three-way crossover trial. The trial will include subjects suspected to have adult growth hormone deficiency (AGHD) and a group of healthy control subjects.
Detailed description
Trial subjects will be assigned to groups of descending likelihood of having AGHD: Group A: High likelihood of AGHD Group B: Intermediate likelihood of AGHD Group C: Low likelihood of AGHD Group D: Healthy control subjects matched to Group A. The sequential of the GHSTs for Group A-C will be determined by randomization. Group D will undergo testing in the same sequence as their matched Group A counterparts Serum growth hormone (GH) concentrations will be measured at predefined time points before and after GHST with GS3-007a or insulin. The peak GH value and diagnostic cut-off for GS3-007a dry suspension will be evaluated using receiver operating characteristic (ROC) curves. Safety, pharmacokinetics (PK), and pharmacodynamics (PD) outcomes were assessed for GS3-007a. The Insulin Tolerance Test (ITT) served as the comparator to determine positive and negative agreement with GS3-007a GHSTs.
Interventions
GS3-007a dry suspension, low dose body weight, drinking solution, single dose GS3-007a dry suspension, high dose body weight, drinking solution, single dose
DRUGInsulin
Insulin, 0.10 -0.15 U/kg, intravenous injection, single dose
Sponsors
Changchun GeneScience Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Suspected AGHD Subjects (Groups A, B, and C): * Age ≥ 18 years and ≤ 65 years, male or female. * Suspected AGHD, meeting at least one of the following criteria: * Congenital structural/gene defects in the hypothalamus or pituitary gland, or * History of surgery or radiotherapy in the hypothalamic or pituitary region, or * Adult traumatic brain injury (TBI) or central nervous system (CNS) infection, or * Confirmed deficiency of at least one pituitary hormone other than growth hormone (GH), or * Idiopathic childhood-onset GHD. * IGF-1 SDS \< 0. * Willing and able to comply with the study procedures and voluntarily sign the informed consent form. Matched Healthy Control Subjects (Group D): * Age ≥ 18 years and ≤ 65 years, male or female. * Matching criteria with Group A (subjects with highly suspected AGHD): 1. Sex; 2. Age; 3. BMI; 4. (If feasible) Estrogen use and administration route (oral, transdermal) in females:
Exclusion criteria
* Known or suspected hypersensitivity to growth hormone secretagogues (GHS) or their excipients or known allergy to insulin or its excipients. * Clinically significant conditions newly diagnosed within 6 months before screening, making the subject unsuitable for ITT: 1. Chronic congestive heart failure (New York Heart Association (NYHA) Class III or higher); 2. Other significant cardiovascular/cerebrovascular diseases, e.g., uncontrolled severe hypertension, severe arrhythmia, stroke or transient ischemic attack (TIA), or confirmed coronary artery disease; 3. Traumatic brain injury (TBI). * Short-acting GH therapy within 30 days before screening. * Long-acting GH therapy within 90 days before screening. * GH stimulation test performed within 7 days before the first dose. * Abnormal thyroid function during screening, or any adjustment to thyroid hormone replacement therapy dosage prior to the first study dose. * Abnormal gonadal function during screening, or any adjustment to testosterone/estrogen replacement therapy dosage prior to the first study dose. * Abnormal adrenal function during screening, or any adjustment to glucocorticoid replacement therapy dosage prior to the first study dose. * Type 1 diabetes diagnosed before screening, or uncontrolled Type 2 diabetes * Body mass index (BMI) ≥40.0 kg/m². * Major surgery (e.g., coronary bypass, hepatectomy/nephrectomy, gynecologic surgery) within 6 months before screening. * Acute neurological, digestive, respiratory, circulatory, endocrine, or hematologic diseases within 3 months before screening, judged by the investigator to potentially affect drug absorption, distribution, metabolism, excretion (ADME), or safety evaluation. * History or current diagnosis of malignancy (any type) before screening. * Electrocardiogram (ECG) findings during screening indicating QTc interval \>450 ms, or history of corrected QT interval (QTc) prolongation, or other clinically significant ECG abnormalities, or use of medications known to prolong QTc interval. * Sellar region MRI scan during screening showing untreated intracranial tumor growth. * History of clinically symptomatic psychiatric disorders persisting at screening. * History of Parkinson's disease or epilepsy persisting at screening. * Females with positive blood human chorionic gonadotropin (hCG) during screening, or lactating females, or females planning pregnancy from screening through follow-up completion. * Liver function abnormalities during screening * Use of medications directly affecting pituitary GH secretion or somatostatin-releasing drugs within a period \>5 half-lives before first study dose. * Use of strong cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5) inhibitors or inducers. * Participation in any other drug or medical device clinical trial within 1 month prior to screening, or screening occurring within 5 half-lives of the investigational drug (whichever is longer). * Unwillingness to use protocol-specified contraception methods * Other conditions deemed by the investigator to make the subject unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ROC curves and the area under the curve (AUC) of the ROC curves | up to 120minutes |
Secondary
| Measure | Time frame |
|---|---|
| Youden index of the ROC curve for GS3-007a dry suspension | up to 120minutes |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 22 days |
Countries
China
Outcome results
None listed