A Study of GS3-007a for Oral Suspension in the Diagnosis of Adult Growth Hormone Deficiency (AGHD)

Phase II Clinical Study of Single Oral Administration of GS3-007a for Oral Suspension in the Diagnosis of AGHD: A Multicenter, Randomized, Open-Label, Three-Way Crossover Trial

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.

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.

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.