Overweight and Obesity
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGLAE103 injection
subcutaneous injection of LAE103 alone
DRUGLAE102 injection in combined with LAE103 injection
LAE102 injection in combined with LAE103 injection via subcutaneous
DRUGSaline
Saline via subcutaneous
Sponsors
Laekna Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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: 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. Part B: Female participants aged 45 to 75 years, inclusive. 3. BMI at screening: 1. Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive). 2. Part B: Have a BMI within the range of 20.0 to 40.0 kg/m2 (inclusive). 4. For female participants: 1. 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 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 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-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 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 1. Are overtly healthy participants, as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECG. 2. Have FSH levels ≥ 40 IU/L at screening (Part B only). 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. 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. 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. 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
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: 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. Part B: Female participants aged 45 to 75 years, inclusive. 3. BMI at screening: 1. Parts A, C, and D: Have a BMI within the range of 25.0 to 40.0 kg/m2 (inclusive). 2. Part B: Have a BMI within the range of 20.0 to 40.0 kg/m2 (inclusive). 4. For female participants: 1. 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 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 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-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). 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number & severity of participants with treatment-related adverse events | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | evaluate the maximum observed serum concentration(Cmax) via LAE103 injection mono or LAE102 combined with LAE103 injection |
| 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. | evaluate what time to reach the maximum serum concentration(Tmax) |
| 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 area under the serum concentration versus time curve (AUC) in LAE103 mono injection or LAE102 combined with LAE103 injection |
| 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. | The validated methodology was employed to assay serum levels of Activin A in biological samples. |
| 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. | Test ADA status in biological sample via validated methodology |
Countries
Australia
Contacts
CONTACTJuan Liu
Outcome results
None listed