NCT07230496招募中1 期
A Phase I, Randomized, Double-blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LAE103 as Single and Multiple Ascending Doses in Healthy Overweight/Obese Participants, and as Single Dose in Healthy Postmenopausal Women, With an Additional Evaluation of Single Ascending Dose of LAE103 in Combination With LAE102 in Healthy Overweight/Obese Participants
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 3
- 主要终点
- Number & severity of participants with treatment-related adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of LAE103 injection in healthy overweight/obese participants or healthy postmenopausal women. Study will also evaluate the safety, tolerability and preliminary pharmacodynamic effect of multiple dose injections in overweight/obese participants.
In addition, the study will also investigate the safety, tolerability of a single-dose co-administration of LAE102 and LAE103 in healthy overweight/obese participants.
详细描述
This is a randomized, double-blind study comprising of a single-dose escalation study in healthy overweight/obese participants (Part A), a single dose study in healthy postmenopausal women (Part B), and a multiple-dose escalation study in healthy overweight/obese participants (Part C), designed to evaluate the safety, tolerability, Pharmacokinetics (PK )and pharmacodynamics (PD) profiles of LAE103 administered alone.
In addition, the study will also investigate the safety, tolerability, and PK/PD profiles of a single-dose co-administration of LAE102 and LAE103 in healthy overweight/obese participants (Part D).
About 104 participants will be enrolled in 13 cohorts with each cohort including 8 participants randomized 6:2 study drug:Placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Informed consent: Are capable of giving signed informed consent and comply with the requirements and restrictions listed in the ICF and in this protocol.
- •Age at the time of signing the ICF:
- •Parts A, C, and D: Male or female participants aged 18 to 55 years, inclusive. Each cohort must include at least 3 female and 3 male participants.
- •Part B: Female participants aged 45 to 75 years, inclusive.
- •BMI at screening:
- •Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive).
- •Part B: Have a BMI within the range of 20.0 to 40.0 kg/m2 (inclusive).
- •For female participants:
- •Participants without childbearing potential: defined as either postmenopausal or surgically sterile: including surgical sterilization (recorded bilateral salpingectomy, hysterectomy, or bilateral oophorectomy at least 6 weeks before screening visit); postmenopausal women defined as an individual who has had at least 12 months of spontaneous amenorrhea without an alternative medical cause and a FSH level in the postmenopausal range (≥ 40 IU/L at screening), or
- •Participants with childbearing potential, non-pregnant, non-lactating, must agree to use two forms of effective methods of contraception (at least one form must be highly effective) for the duration of the study, and 130 days after the last investigational product administration. During this period, participants should not donate eggs. Serum hCG test must < 5 mIU/mL at both the screening visit and D-
- •Hormonal contraceptives should be commenced one month prior to screening to ensure contraceptive is in full effect.
- •Complete abstinence is acceptable if it is part of the participant's usual and preferred lifestyle. Participants who are in same-sex relationships and continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as per protocol (This would only apply to Parts A, C, and D, details of contraception guidance refer to 12.3).
- •Male participants with female partners of childbearing potential must agree to use adequate methods of contraception, which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner for the duration of the study and for 130 days after the last dosing. Male participants are not allowed to donate sperm for the same period. Hormonal contraceptives used by the female partner should have commenced one month prior to screening to ensure contraceptive is in full effect.
- •Type of participant and disease characteristics
- •Are overtly healthy participants, as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG.
- •Have FSH levels ≥ 40 IU/L at screening (Part B only).
- •Have liver function tests and all other clinical laboratory tests results within the normal range for the population, or results deemed not clinically significant at the discretion of the investigator.
- •Note: except for minor deviation judged to be acceptable by the investigator. Retesting may occur once during the screening visit at the discretion of the investigator.
- •Have venous access sufficient to allow for blood sampling as per the protocol or have no anticipated contraindications to receiving investigational products via SC delivery.
- •Are willing to make themselves available for study visits for the duration of the study and are willing to follow study procedures.
- •Note: For Part D optional cohort, inclusion criteria for the additional 2 postmenopausal women can be referred to Part B if their enrollment is planned
排除标准
- •Informed consent: Are capable of giving signed informed consent and comply with the requirements and restrictions listed in the ICF and in this protocol.
- •Age at the time of signing the ICF:
- •Parts A, C, and D: Male or female participants aged 18 to 55 years, inclusive. Each cohort must include at least 3 female and 3 male participants.
- •Part B: Female participants aged 45 to 75 years, inclusive.
- •BMI at screening:
- •Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive).
- •Part B: Have a BMI within the range of 20.0 to 40.0 kg/m2 (inclusive).
- •For female participants:
- •Participants without childbearing potential: defined as either postmenopausal or surgically sterile: including surgical sterilization (recorded bilateral salpingectomy, hysterectomy, or bilateral oophorectomy at least 6 weeks before screening visit); postmenopausal women defined as an individual who has had at least 12 months of spontaneous amenorrhea without an alternative medical cause and a FSH level in the postmenopausal range (≥ 40 IU/L at screening), or
- •Participants with childbearing potential, non-pregnant, non-lactating, must agree to use two forms of effective methods of contraception (at least one form must be highly effective) for the duration of the study, and 130 days after the last investigational product administration. During this period, participants should not donate eggs. Serum hCG test must < 5 mIU/mL at both the screening visit and D-
- •Hormonal contraceptives should be commenced one month prior to screening to ensure contraceptive is in full effect.
- •Complete abstinence is acceptable if it is part of the participant's usual and preferred lifestyle. Participants who are in same-sex relationships and continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as per protocol (This would only apply to Parts A, C, and D, details of contraception guidance refer to 12.3). LAEKNA LAE103INT1001 Protocol Version 5.0/2026.08.31 CONFIDENTIAL Page 74 of 1455) Male participants with female partners of childbearing potential must agree to use adequate methods of contraception, which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner for the duration of the study and for 130 days after the last dosing. Male participants are not allowed to donate sperm for the same period. Hormonal contraceptives used by the female partner should have commenced one month prior to screening to ensure contraceptive is in full effect.
- •6) Type of participant and disease characteristics
- •a) Are overtly healthy participants, as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. b) Have FSH levels ≥ 40 IU/L at screening (Part B only). c) Have liver function tests and all other clinical laboratory tests results within the normal range for the population, or results deemed not clinically significant at the discretion of the investigator. Note: except for minor deviation judged to be acceptable by the investigator. Retesting may occur once during the screening visit at the discretion of the investigator. d) Have venous access sufficient to allow for blood sampling as per the protocol or have no anticipated contraindications to receiving investigational products via SC delivery.
- •7) Are willing to make themselves available for study visits for the duration of the study and are willing to follow study procedures. Note: For Part D optional cohort, inclusion criteria for the additional 2 postmenopausal women can be referred to Part B if their enrollment is planned
- •Exclusion Criteria:
- •Medical Conditions:
- •Have a history or presence of clinically significant medical condition(s) including, but not limited to, any
- •cardiovascular, cerebrovascular, gastrointestinal (including hepatic) diseases.
- •diabetes, or glycated hemoglobin (HbA1c) ≥ 6.5% or fasting blood glucose ≥ 7.0 mmol/L, medullary thyroid carcinoma, type 2 multiple endocrine neoplasia, chronic pancreatitis, and thyroid disorders.
- •Note: Participants who have been on steady dose of thyroid replacement therapy for at least 90 days prior to screening, can be included in the study.
- •conditions affecting skin, respiratory, cardiovascular, digestive, renal, blood, endocrine,reproductive system.
- •diagnosed with secondary overweight or obesity, such as obesity caused by metabolic diseases (such as Cushing's syndrome, hypothyroidism, etc.) or drug-induced obesity(such as glucocorticoids, tricyclic antidepressants, atypical antipsychotic drugs, etc.).
- •psychiatric or neurological disease.
- •neuromuscular disorder including, but not limited to multiple sclerosis, myasthenia gravis, myopathy, peripheral neuropathy, muscular dystrophy, or amyotrophic lateral sclerosis.
- •inflammatory or autoimmune diseases that may cause muscle wasting, including, but not limited to systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).
- •inflammatory myopathies, including but not limited to polymyositis or dermatomyositis.
- •other disease, abnormality or physiological conditions that would pose an unacceptable risk to study participants or confound the interpretation of the data collected during the study.
- •individuals who have had a diagnosis of acute pancreatitis.
- •individuals who have self-perceived dullness or loss of sensation on either side of their abdomen; or have, in the investigator's opinion, excessive tattoos or scars over the arm, thigh, abdomen or other factors (for example rash, excessive fold of skin) that, would interfere with injection-site assessments.
- •Have a history of any malignancy within the past 5 years other than
- •basal cell or squamous epithelial carcinomas in situ,
- •cervical carcinoma in situ that have been resected with no evidence of metastatic diseases for 3 years.
- •Have a fasting serum triglyceride level of more than 500 mg/dL(5.6 mmol/L) at screening.
- •Have an estimated glomerular filtration rate (eGFR) calculated by chronic kidney diseaseepidemiology (CKD-EPI) creatinine 2021 equation
- •less than 90 mL/min/1.73 m2 at screening for Part A, C, and Part D
- •less than 60 mL/min/1.73 m2 at screening for Part B. Note: Creatine level within normal range, or out of the normal range but deemed nonclinically significant by the investigator can be enrolled.
- •an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study, or
- •confirmed supine Fridericia's corrected QT (QTcF) interval greater than 450 msec for males and greater than 470 msec for females at screening.
- •Note: A mean value will be used to assess the exclusion criterion when triplicate measurements will be made as per protocol.
- •Have an abnormal blood pressure defined as:
- •diastolic blood pressure greater than 90 mmHg, or less than 50 mmHg
- •systolic blood pressure greater than 140 mmHg, or less than 90 mmHg Note: except for minor deviation judged to be acceptable by the investigator, or mild to moderate hypertension that is well-controlled with no more than one antihypertensive medication and no changes to hypertension medication within the last three months. Retesting may occur once during the screening visit at the discretion of the investigator.
- •Show evidence at screening of:
- •human immunodeficiency virus (HIV) or positive human HIV antibodies
- •hepatitis C or positive hepatitis C antibodies
- •hepatitis B or positive hepatitis B surface antigen.
- •a history of, or known hypersensitivity to study intervention or its excipients, or
- •a history of, or know hypersensitivity to monoclonal antibody drugs, or
- •a history of any severe allergies (including any food or drug allergies).
- 另有 33 项未显示
研究组 & 干预措施
Treatment arm of single drug
Experimental
LAE103 injection, subcutaneous (SC) injection
干预措施: LAE103 injection (Drug)
Treatment arm of single drug
Experimental
LAE103 injection, subcutaneous (SC) injection
干预措施: Saline (Drug)
Treatment arm of combination
Experimental
LAE102 injection combined with LAE103 injection, subcutaneous (SC) injection
干预措施: LAE102 injection in combined with LAE103 injection (Drug)
comparator arm
Placebo Comparator
Saline
干预措施: Saline (Drug)
Treatment arm of combination
Experimental
LAE102 injection combined with LAE103 injection, subcutaneous (SC) injection
干预措施: Saline (Drug)
结局指标
主要结局
Number & severity of participants with treatment-related adverse events
时间窗: From Day1 to Day112 for single dose part.From Day1 to Day84 for Combination Drug Part. From Day 1 to Day140 for multiple dose part.
Findings on physical examination, ECG, vital signs, and reports of the laboratory results via investigator assessment
Number & severity of participants with treatment-related adverse events
时间窗: From Day1 to Day70 for single dose part. From Day 1 to Day98 for multiple dose part
Findings on physical examination, ECG, vital signs, and reports of the laboratory results via investigator assessment
次要结局
- characterize the peak of serum concentration (Cmax)(From Day1 to Day112 for single dose part.From Day1 to Day 84 for Combination Drug Part. From Day 1 to Day140 for multiple dose part.)
- characterize the time of reaching peak of serum concentration (Tmax)(From Day1 to Day112 for single dose part.From Day 1 to Day 84 for Combination Drug Part. From Day 1 to Day140 for multiple dose part.)
- characterize the area under the serum concentration versus time curve (AUC)(From Day1 to Day112 for single dose part.From Day1 to Day 84 for Combination Drug Part. From Day 1 to Day140 for multiple dose part.)
- Evaluate the expression levels of Activin A in blood samples(From Day1 to Day112 for single dose part.From Day 1 to Day 84 for Combination Drug Part. From Day 1 to Day140 for multiple dose part.)
- Incidence of positive Anti-drug antibody(ADA) after administration(From Day1 to Day112 for single dose part.From Day1 to Day 84 for Combination Drug Part. From Day 1 to Day140 for multiple dose part.)
- characterize the peak of serum concentration (Cmax)(From pre-dose to Day70 for single dose part. From pre-dose to Day98 for multiple dose part)
- characterize the time of reaching peak of serum concentration (Tmax)(From pre-dose to Day70 for single dose part. From pre-dose to Day98 for multiple dose part)
- characterize the area under the serum concentration versus time curve (AUC)(From pre-dose to Day70 for single dose part. From pre-dose to Day98 for multiple dose part)
- Incidence of positive Anti-drug antibody(ADA) after administration(From pre-dose to Day70 for single dose part. From pre-dose to Day98 for multiple dose part.)
- Evaluate the expression levels of Activin A in blood samples(From pre-dose to Day70 for single dose part. From pre-dose to Day98 for multiple dose part.)
研究者
研究点 (3)
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