A Single Ascending Dose Study of SYH2082 Injection in Healthy Participants

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Dose of SYH2082 Injection in Healthy Participants

Обзор

To evaluate the safety and tolerability of single dose of SYH2082 Injection in healthy participants.

Вмешательства

• Препарат SYH2082 Injection
  A subcutaneous injection in the abdomen of the corresponding dose of SYH2082 Injection according to the assigned dose cohort.
• Препарат Placebo
  A subcutaneous injection in the abdomen of the corresponding dose of Placebo according to the assigned dose cohort.

Первичные конечные точки

• Number of Adverse Events as a measure of safety and tolerability of SYH2082 [Срок оценки: Screening period up to day 57]

Вторичные конечные точки (12)

• Maximum plasma concentration (Cmax) [Срок оценки: Pre-dose at day 1 to day 57]
• Area under the concentration-time curve from time 0 to the last measurable time point (AUClast) [Срок оценки: Pre-dose at day 1 to day 57]
• Area under the concentration time curve from time 0 to infinity (AUCinf) [Срок оценки: Pre-dose at day 1 to day 57]
• Time to maximum concentration (Tmax) [Срок оценки: Pre-dose at day 1 to day 57]
• Elimination half-life (t1/2) [Срок оценки: Pre-dose at day 1 to day 57]
• Apparent volume of distribution (Vz/F) [Срок оценки: Pre-dose at day 1 to day 57]
• Apparent clearance (CL/F) [Срок оценки: Pre-dose at day 1 to day 57]
• Anti-SYH2082 antibodies [Срок оценки: Pre-dose at day 1 to day 57]
• Change in fasting plasma glucose from baseline [Срок оценки: Baseline up to Day 57]
• Change in fasting insulin from baseline [Срок оценки: Baseline up to Day 57]
• Change in C-peptide from baseline [Срок оценки: Baseline up to Day 57]
• Change in glucagon from baseline [Срок оценки: Baseline up to Day 57]

Критерии участия

Критерии включения

• Fully understands the content, procedures, and possible adverse reactions of the study, and voluntarily signs the ICF before the study;
• At screening, age 18-65 years (inclusive, at the time of signing the ICF), male or female;
• At screening, body weight ≥50 kg for males and ≥45 kg for females; body mass index (BMI) between 22.0 and 40.0 kg/m2 (inclusive);
• Body weight change ≤5% within 3 months prior to screening (including the screening period);
• From the time of signing the ICF until 6 months after the last dose, the participant (including their partner) has no plans for childbirth and agrees to use highly effective contraceptive measures.

Критерии исключения

• Known or suspected allergy to glucagon-like peptide-1 (GLP-1) or Glucose dependent insulinotropic polypeptide (GIP) receptor agonists or any component of the investigational product; or has an allergic constitution (allergic to multiple drugs and foods);
• Abnormal results in vital signs, physical examination, laboratory tests, and ECG that are judged by the investigator to be clinically significant within the screening period. Specifically, the following conditions are not excluded:

• Systolic blood pressure (SBP) < 160 mmHg, diastolic blood pressure (DBP) < 100 mmHg;
• Fasting TG ≤ 5.6 mmol/L, fasting TC ≤ 7.5 mmol/L, fasting LDL-C ≤ 5 mmol/L, and abnormal fasting HDL-C;
• Alanine aminotransferase (ALT) < 2 × ULN, aspartate aminotransferase (AST) < 2 × ULN, gamma-glutamyl transferase (GGT) < 2.5 × ULN, and total bilirubin (TBIL) < 1.5 × ULN. Participants with values outside the normal range may be included if the abnormality is deemed benign by the investigator (e.g., Gilbert's syndrome);
• History or laboratory evidence of diabetes mellitus (type 2, type 1, or other forms of diabetes), including fasting glucose of ≥126 mg/dL (7.0 mmol/L) and/or HbA1c ≥ 6.5% within the screening period;
• With any previous episode of hypoglycemia or with screening fasting glucose < 3.9mmol/L (even on a single sample);
• With obesity due to identifiable endocrinologic, genetic or syndromic causes;
• Meets any of the following criteria within the screening period:

• Calcitonin ≥25 ng/L;
• Estimated glomerular filtration rate (eGFR) <80 mL/min/1.73m2
• Thyroid-stimulating hormone (TSH) outside the normal reference range;
• Fasting serum amylase and/or lipase >1.5× ULN.
• At screening, has a prolonged QT/QTc interval (QTcF >450 ms for males and QTcF>470 ms for females), or a history of risk factors for Torsades de Pointes (e.g., cardiac failure/cardiomyopathy or a family history of long QT syndrome), or is currently taking concomitant medications that prolong the QT/QTc interval;
• Positive for any of the following: Hepatitis B surface antigen, Hepatitis C virus antibody, human immunodeficiency virus antibody, or syphilis serology;
• Significant history or clinical manifestation of any metabolic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, immune or psychiatric disorder as determined by the Investigator or medical designees;
• History of severe trauma or major surgery within 3 months prior to screening, or plans to undergo surgery or any procedures requiring general anesthesia or sedation during the study period;
• History of thyroid nodules diagnosed as C-TIRADS category 3 or higher;
• Personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia syndrome type 2, or a personal history of pancreatitis or gallbladder/gallstone disease;
• History of malignancy, except for non-melanoma skin cancer excised more than 1 year prior to Screening and cervical intraepithelial neoplasia that has been successfully cured more than 2 years prior to Screening;
• History of major depressive disorder, including any medication or psychological therapy, in the last 2 years, or any clinically significant mental health condition;
• Lifetime history of any suicide attempts or suicide behavior according to the C-SSRS, or any suicidal ideation in the last two years according to the C-SSRS;
• Non-suicidal self-injury more than 5 years ago is permissible, if it is clear there was no suicidal intent. Participants should be excluded if any doubt;
• History of gastric emptying abnormalities (e.g., gastric outlet obstruction) or severe chronic gastrointestinal diseases (e.g., inflammatory bowel disease, active ulcer);
• History of gastrointestinal surgery that could lead to malabsorption, or long-term use of drugs that directly affect gastrointestinal motility. For example: has undergone bariatric surgery or procedures (e.g., gastric banding) within 3 months prior to screening;
• History of use GLP-1 or GIP receptor agonists or any drug or product that may cause weight changes and affect weight assessment considered by the investigator within 3 months prior to screening;
• Has dermatitis or other skin abnormalities (including tattoos) at or around the injection site;
• Use of any prescription drugs, within 2 weeks prior to dosing or no more than 5 half-life (whichever is longer) after the last use of the above drugs. Non-prescription drugs, herbal preparations and supplements excluded 7 days prior to dosing, and allow short term use of paracetamol and anti-inflammatory drug use within the 7 days prior to dosing, within investigator discretion;
• Use of drugs that may affect glucose metabolism (e.g., systemic steroids, non-selective β-blockers, monoamine oxidase inhibitors) within 1 month prior to screening, or no more than 5 half-life (whichever is longer) after the last use of the above drugs;
• Average weekly alcohol consumption exceeding 21 units (males) / 14 units (females) within 3 months prior to screening (1 unit ≈ 375 mL of mid-strength beer (3.5% alcohol/volume), 100 mL of wine (13.5% alcohol/volume), or 30 mL of spirits (40% alcohol/volume)), or has a positive alcohol breath test, or is unable to abstain from alcohol during the hospital stay;
• Smokes more than 10 cigarettes per day on average within 3 months prior to screening, or is unable to stop using any nicotine products during the hospital stay;
• Consumes excessive amounts of tea, coffee, and/or caffeinated beverages (average of more than 8 cups per day, 1 cup ≈ 250 mL) within 3 months prior to screening, or is unable to stop consumption during the hospital stay;
• Engaged in strenuous exercise within 48 hours prior to clinic visits, such as weightlifting, sprinting, long-distance running, cycling, swimming, or playing football;
• History of drug abuse within 6 months prior to screening, or a positive drug abuse screening test at screening and D-2;
• Has donated blood or plasma within 30 days prior to screening or had a loss of whole blood of more than 500ml within the 30 days prior to screening, or receipt of a blood transfusion within one year prior to screening;
• History of needle or blood phobia, difficulty with blood collection, or unable to tolerate intravenous blood draws;
• Has special dietary requirements and cannot adhere to the standardized diet and schedule;
• Female participants who are pregnant, lactating, or have a positive pregnancy test result at screening and D-2;
• Has received an investigational agent/device in another clinical study within 3 months or 5 half-lives prior to Screening (whichever is longer), or is currently participating in or plans to participate in another drug or medical device clinical study during the study period;
• Participants whom the investigator considers to have other factors making them unsuitable for participation in this trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07532655 · SYH2082-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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