A Clinical Study of GenSci134 in Healthy Adults and Adult Growth Hormone Deficiency(AGHD)

A Phase I, Randomized, Double-blind, Placebo and Active-controlled Study of Single and Multiple Ascending Doses of GenSci134 Injection in Healthy Adults, and a Single Ascending Dose in Patients With Adult Growth Hormone Deficiency

To check how safe and well-tolerated a single subcutaneous injection of GenSc134 is in healthy male volunteers， a multiple-doses subcutaneous injection of GenSc134 is in healthy volunteers，a single subcutaneous injection of GenSc134 is in AGHD patients.

This study consists of two parts: the first part is the study in healthy volunteers, and the second part is the study in AGHD patients.

The first part consists of two phases. Phase Ia is a single-ascending dose study in healthy male volunteers, and Phase Ib is a multiple-ascending dose study healthy male or female volunteers.

The second part is Phase Ic，which is a a single-ascending dose study in AGHD patients.

Phase Ia：GenSci134 was tested in 7 predetermined single dose groups with placebo and positive drug controls to explore the dosage, and to assess its safety, tolerability, pharmacokinetic (PK) characteristics, pharmacodynamic (PD) characteristics, immunogenicity, and exploratory endpoints in 64 healthy adult male volunteers.

Phase Ib：GenSci134 was tested in 3 predetermined multiple dose groups with placebo, and to assess its safety, tolerability, pharmacokinetic (PK) characteristics, pharmacodynamic (PD) characteristics, immunogenicity in 36 healthy adult volunteers.

Phase Ic :GenSci134 was tested in 2 predetermined dose groups with positive drug controls to explore the dosage, and to assess its safety, tolerability, pharmacokinetic (PK) characteristics, pharmacodynamic (PD) characteristics, immunogenicity, and exploratory endpoints in 16 AGHD patients.

Inclusion Criteria:

The first part in Healthy adult volunteers:

• Healthy adult male subjects（Phase Ia），or Healthy adult subjects（Phase Ib） aged 18-45 years (inclusive of boundary values);
• Body Mass Index (BMI): 19.0-24.0 kg/m² (inclusive of boundary values);
• Good health status;
• Able to understand and willing to sign the Informed Consent Form (ICF), and comply with study requirements and restrictions.

The second part in AGHD patients（Phase Ic）:

• Be able to understand and be willing to sign the written ICF (before any study procedure is performed).
• Be willing and able to comply with scheduled visits, treatment regimens, laboratory tests, and other specified study procedures.
• Aged from 20 to 70 years old (inclusive), at the time of signing the ICF.
• Body mass index (BMI): 18.0-32.0 kg/m² ((inclusive of boundary values).
• Meeting any of the following diagnostic criteria for growth hormone deficiency:
• Adult-onset: Participants with GHD due to hypothalamo-pituitary disorder or relevant treatments (surgery, radiotherapy) or other reasons (infection, traumatic craniocerebral injury, etc.); the participant has no relapse or residual disease is stable for more than 1 year after surgery for pituitary adenoma, surgery for craniopharyngioma or other pituitary gland operation.
• Childhood-onset: Participants with childhood idiopathic, acquired, congenital GHD or childhood GHD for other reasons.
• Confirmed diagnosis of AGHD (meeting at least one of the following criteria):
• Insulin tolerance test: peak GH cut-off point ≤ 5 μg/L.
• Glucagon challenge test:
• a) Participants with BMI < 25 kg/m² or high clinical suspicion [≥ 3 pituitary hormone deficiencies (PHDs)] with BMI 25-30 kg/m², peak GH ≤ 3 μg/L.
• b) Participants with BMI > 30 kg/m² or low clinical suspicion (≤ 2 PHDs) with BMI 25-30 kg/m², peak GH ≤ 1 μg/L.
• ≥ 3 PHDs and IGF-1 SDS < -2.0 at screening.
• Participants who have not previously received human growth hormone (hGH) therapy or are in the washout period of previous hGH therapy.

Exclusion Criteria:

The first part in Healthy adult volunteers:

• Subjects with significant medical history or clinical manifestations determined by the investigator;
• History of hypersensitivity, intolerance, or allergy to any drug, compound, food, or other substances, or known allergy to any excipients of the study drug;
• History of neurological or psychiatric disorders, or subjects with impaired consciousness or cognitive dysfunction;
• Subjects with clinically significant abnormalities, including but not limited to vital signs or laboratory test results that are abnormal and clinically significant;
• Subjects with immunodeficiency or immunosuppressive diseases at screening;
• Subjects who have undergone major surgery within 12 months prior to screening;
• Subjects with a history of neoplastic diseases;
• Subjects who have participated in any other clinical trial of drugs or medical devices and have used the investigational medicinal product within 28 days or 5 half-lives (whichever is longer) before dosing.

The second part in AGHD patients（Phase Ic）:

• Known or suspected hypersensitivity to the investigational medical product and/or any of its excipients.
• Female participants who are pregnant, breast-feeding or intend to become pregnant or are of childbearing potential but not using an effective contraceptive method.
• Male participants with fertility potential or their partners who do not use an effective contraceptive method.
• Clinically significant hepatic disease.
• Clinically significant chronic renal insufficiency.
• Cardiac failure.
• Use of any investigational product within 30 days prior to screening or participated in another trial within 30 days prior to dosing.
• Use of systemic corticosteroids at non-alternative doses within 90 days prior to dosing.
• Any disorder or treatment which, in the opinion of the investigator, possibly jeopardizes participant's safety or affects his/her compliance with the protocol.
• History of diabetes mellitus.
• History of malignancy or ongoing malignancy.
• Active Cushing's syndrome within 24 months prior to dosing.
• Acute severe diseases resulting in weight loss within 180 days prior to dosing.
• Use of weight-reducing drugs known to affect body weight significantly within 12 months prior to dosing.
• Presence of a mental or language disorder that impairs the ability to understand or cooperate with the study, unwillingness to participate, or any other condition that, in the opinion of the investigator or treating physician, renders the participant unsuitable for the trial.
• Anticipated change in lifestyle during the trial.