Safety and tolerability in healthy overweight/obese volunteers Nutritional, Metabolic, Endocrine
Conditions
Interventions
Study treatment:
Investigational product 1: LAE103
Investigational product 2: LAE102
Placebo: Sodium Chloride
Part A: Healthy overweight/obese volunteers will be randomised sequentially into five sin
Sponsors
Laekna Limited
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Informed consent: Are capable of giving signed informed consent and comply with the requirements and restrictions listed in the ICF and in this protocol. 2. Age at the time of signing the ICF: 2.1. 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. 2.2. Part B: Female participants aged 45 to 75 years, inclusive. 3. BMI at screening: 3.1. Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive). 3.2. Part B: Have a BMI within the range of 20.0 to 35.0 kg/m2 (inclusive). 4. For female participants: 4.1. Participants without childbearing potential: defined as either postmenopausal or surgically sterile: including surgical sterilization; 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 4.2. 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 13 weeks 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-1. 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). 5. 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 22 weeks 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 6.1. Are overtly healthy participants, as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. 6.2. Have FSH levels = 40 IU/L at screening (Part B only). 6.3. 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. 6.4. 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.
Exclusion criteria
Exclusion criteria: 1. Have a history or presence of clinically significant medical condition(s), including, but not limited to, any 1.1. Cardiovascular, cerebrovascular, gastrointestinal (including hepatic) diseases. 1.2. 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. 1.3. Conditions affecting skin, respiratory, cardiovascular, digestive, renal, blood, endocrine, and reproductive systems. 1.4. 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.). 1.5. Psychiatric or neurological disease. 1.6. Neuromuscular disorder, including, but not limited to, multiple sclerosis, myasthenia gravis, myopathy, peripheral neuropathy, muscular dystrophy, or amyotrophic lateral sclerosis. 1.7. Inflammatory or autoimmune diseases that may cause muscle wasting, including, but not limited to, systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). 1.8. Inflammatory myopathies, including but not limited to polymyositis or dermatomyositis. 1.9. 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. 1.10 Individuals who have had a diagnosis of acute pancreatitis. 1.11 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. 2. Have a history of any malignancy within the past 5 years other than 2.1. Basal cell or squamous epithelial carcinomas in situ, 2.2. Cervical carcinoma in situ that has been resected with no evidence of metastatic disease for 3 years. 3. Have a fasting serum triglyceride level of more than 500 mg/dL(5.6 mmol/L) at screening. 4. Have an estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) creatinine 2021 equation 4.1. Less than 90 mL/min/1.73 m2 at screening for Part A, C, and Part D 4.2. Less than 60 mL/min/1.73 m2 at screening for Part B. 5. Have 5.1. An abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study, or 5.2. Confirmed supine Fridericia’s corrected QT (QTcF) interval greater than 450 msec at screening. 6. Have an abnormal blood pressure defined as: 6.1. Diastolic blood pressure greater than 90 mmHg, or less than 60 mmHg 6.2. Systolic blood pressure greater than 140 mmHg, or less than 90 mmHg 7. Show evidence at screening of: 7.1. Human immunodeficiency virus (HIV) or positive human HIV antibodies 7.2. Hepatitis C or positive hepatitis C antibodies 7.3. Hepatitis B or positive hepatitis B surface antigen. 8. Have 8.1. A history of, or known hypersensitivity to study intervention or its excipients, or 8.2. A history of, or known hypersensitivity to monoclonal antibody drugs, or 8.3. A history of any severe allergies (including any food or drug allergies). 9. Underwent major surgery within 30 days prior to study intervention administration or plan to undergo major surgery during the stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part A: Evaluate the safety and tolerability of LAE103 in healthy overweight/obese participants following a single SC injection. Measured through incidence of TEAEs, vital signs, physical examinations, 12-lead ECG, and clinical laboratory tests within 70 days of dose administration. 2. Part B: Evaluate the safety and tolerability of LAE103 in post-menopausal female participants following a single SC injection. Measured through incidence of TEAEs, vital signs, physical examinations, 12-lead ECG, and clinical laboratory tests within 70 days of dose administration. 3. Part C: Evaluate the safety and tolerability of LAE103 in healthy overweight/obese participants following multiple SC injections. Measured through incidence of TEAEs, vital signs, physical examinations, 12-lead ECG, and clinical laboratory tests within 98 days of first dose administration. 4. Part D: Evaluate the safety and tolerability of LAE103 given in combination with LAE102 in healthy overweight/obese participants following a single SC injection. Measured through incidence of TEAEs, vital signs, physical examinations, 12-lead ECG, and clinical laboratory tests within 70 days of dose administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Part A-1: Evaluate the PK profile of LAE103 in healthy overweight/obese participants following a single SC injection. Measured through serum concentrations versus time and PK parameters (Cmax, Tmax, AUC0-t, AUC0-8, t1/2, CL/F (s.c.) , Vz/F (s.c.), etc.) of LAE103 from pre-dose to 70 days post dose. 2. Part A-2: Evaluate the change in serum Activin A levels in healthy overweight/obese participants following a single SC injection of LAE103. Measured through change and percentage change from baseline in serum Activin A levels from pre-dose to 70 days post dose. 3. Part A-3: Evaluate the immunogenicity of LAE103 in healthy overweight/obese participants following a single SC injection. Measured through incidence and titers of positive ADA after administration from pre-dose to 70 days post dose. 4. Part B-1: Evaluate the PK profile of LAE103 in post-menopausal female participants following a single SC injection. Measured through serum concentrations versus time and PK parameters (Cmax, Tmax, AUC0-t, AUC0-8, t1/2, CL/F (s.c.) , Vz/F (s.c.), etc.) of LAE103 from pre-dose to 70 days post dose. 5. Part B-2: Evaluate the change in serum Activin A levels in post-menopausal female participants following a single SC injection of LAE103. Measured through change and percentage change from baseline in serum Activin A levels from pre-dose to 70 days post dose. 6. Part B-3: Evaluate the immunogenicity of LAE103 in post-menopausal female participants following a single SC injection. Measured through incidence and titers of positive ADA after administration from pre-dose to 70 days post dose. 7. Part B-4: Evaluate the effect of LAE103 on FSH levels in healthy postmenopausal women following a single SC injection. Measured through change and percentage change from baseline in FSH levels from pre-dose to 70 days post dose. 8. Part C-1: Evaluate the PK profile of LAE103 in healthy overweight/obese participants following multiple SC injections. Measured through serum concentrations versus | — |
Countries
Australia
Contacts
Public ContactLi;Doris Qiu;Zan
;
Outcome results
None listed