Overweight and Obesity
Conditions
Brief summary
This is a Phase 1/2a, first-in-human, prospective, open-label study to evaluate the safety, tolerability, PK, PD, and effect on body weight of TE-8105 in overweight/obese participants without diabetes. Study TE-8105-101 consists of 2 parts: Part A (single-ascending dose \[SAD\]) and Part B (multiple-ascending dose \[MAD\])
Detailed description
Part A consists of 4 cohorts, with an optional adaptive cohort which may be opened if needed approximately 24 eligible participants will be assigned to Part A (SAD) (6 participants in each cohort). Part A is designed to evaluate the safety, tolerability, PK and effect on body weight of a single dose of 0.5 mg, 0.75 mg, 1.5 mg (or ≤ 2.5 mg), 3 mg (or ≤ 5 mg) TE-8105. Each participant will receive one dose of TE-8105 injection via subcutaneous (SC) injection into the abdomen administered on Day 1. Part B consists of 2 cohorts. Approximately 14 participants will be assigned to Part B (MAD) (6 participants in B1 and 8 in B2 cohort). Part B is designed to evaluate the safety, tolerability, PK, PD, and effect on body weight of multiple SC doses 0.5 mg up to 3mg TE-8105 once every 2 weeks (Q2W). The dose levels and dosing interval of Part B may be adjusted based on the results of Part A. Each participant will receive 5 doses or 9 doses of TE-8105 injection via SC injection into the abdomen. Progression from Part A to Part B will be based on the recommendation of the SRC.
Interventions
DRUGTE-8105 SAD Cohort 1
Each participant will receive one dose of TE-8105 0.5 up to 1.5mg injection via subcutaneous (SC) injection into the abdomen administered on Day 1.
DRUGTE-8105 SAD Cohort 3
Each participant will receive one dose of TE-8105 1.5 mg or less than or equal to 2.5 mg injection via subcutaneous (SC) injection into the abdomen administered on Day 1.
DRUGTE-8105 SAD Cohort 5 (Adaptive cohort)
Each participant will receive one dose of TE-8105 less than or equal to 6 mg injection via subcutaneous (SC) injection into the abdomen administered on Day 1.
DRUGTE-8105 MAD Cohort 1
Each participant will receive 0.5mg up to 1.5mg of TE-8105 injection via SC injection into the abdomen on Day 1 and then once every 2 weeks for 5 doses.
DRUGTE-8105 MAD Cohort 2
Each participant will receive 9 doses of TE-8105 injection via SC injection into the abdomen starting from Day 1 every 2 weeks. Dose will be titrated up by 0.5mg every 4 weeks, with dose levels of 1.5mg (2 doses), 2.0 mg (2 doses), 2.5 mg (2 doses) and 3.0 mg (3 doses)
DRUGTE-8105 SAD Cohort 2
Each participant will receive one dose of TE-8105 0.75mg injection via subcutaneous (SC) injection into the abdomen on Day 1.
DRUGTE-8105 SAD Cohort 4
Each participant will receive one dose of TE-8105 3 mg or less than or equal to 5 mg injection via subcutaneous (SC) injection into the abdomen administered on Day 1.
Sponsors
Immunwork, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Adults who are overweight or obese, do not have diabetes, and who are otherwise healthy, will be recruited. Main inclusion /
Exclusion criteria
include but are not limited to: * Male or female between 18 and 65 years old (both inclusive, at the time of informed consent). * Have a BMI of ≥ 25 and ≤ 34.9 kg/m² or ≥ 23 and ≤ 32.5 kg/m² for Asian and Aboriginal participants. * Have a stable body weight, defined as \< 5% change in body weight, in either direction, during the Screening period (Day -28 to Day -1). * Hemoglobin A1C (HbA1c) \< 6.5%. * Able and willing to provide written informed consent and any locally required authorization before performing any protocol-related procedures, including screening evaluations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with changes in respiratory rate (RR) | SAD: Scr, D-1, D1, D2, D3, D5, D8, D15, D43; MAD B1: Scr, D-1, D1, D2, D3, D8, D15, D29, D43, D57, D64, D71, D92, D113, D134; MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | — |
| Number of participants with change in serum blood parameters | SAD: Scr, D-1, D2, D3, D8, D15, D29, D43 post dose. MAD B1: Scr, D-1, D2, D3, D8, D15, D29, D43, D57, D71, D92, D113, D134 post dose. MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | Laboratory assessment includes Hematology, coagulation and serum chemistry. |
| Number of participants with change in urine parameters | SAD: Scr, D-1, D2, D3, D8, D15, D29, D43 post dose. MAD B1: Scr, D-1, D2, D3, D8, D15, D29, D43, D57, D71, D92, D113, D134 post dose. MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | Laboratory assessment includes urinalysis |
| Number of participants with changes in the physical examination findings | Scr, D-1, D3, D8, D15 and D43 post dose. MAD B1: Scr, D-1, D3, D8, D15, D29, D43, D57, D71, D92, D113, D134 post dose. MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | Complete physical examinations include: general appearance, head, ears, eyes, nose, throat, neck (including thyroid and nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, skin, and other. |
| Number of participants with changes in 12 lead ECG findings | Scr, D-1, D1, D2, D3, D8, D15, D43 post dose. MAD B1: Scr, D-1, D1, D2, D3, D8, D15, D29, D43, D57, D71, D92, D113, D134 post dose. MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | ECG measurements to include Heart rate, PR, QRS, QT, and QTcF intervals. |
| Number of participants with changes in temperature | SAD: Scr, D-1, D1, D2, D3, D5, D8, D15, D43; MAD B1: Scr, D-1, D1, D2, D3, D8, D15, D29, D43, D57, D64, D71, D92, D113, D134; MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | — |
| Number of participants with changes in blood pressure (BP) | SAD: Scr, D-1, D1, D2, D3, D5, D8, D15, D43; MAD B1: Scr, D-1, D1, D2, D3, D8, D15, D29, D43, D57, D64, D71, D92, D113, D134; MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | Systolic and diastolic BP will be measured |
| Number of participants with changes in heart rate (HR) | SAD: Scr, D-1, D1, D2, D3, D5, D8, D15, D43; MAD B1: Scr, D-1, D1, D2, D3, D8, D15, D29, D43, D57, D64, D71, D92, D113, D134; MAD B2: Scr, D-1, D2, D3, D5, D8, D15, D29, D43, D57, D71, D85, D99, D113, D117, D120, D127, D141 and D155 post dose | — |
| Safety and tolerability of TE-8105 by the incidence of treatment-related adverse events | SAD: From Screening until Day 43 (End of study) post dose. MAD: From Screening until Day 134 in Cohort B1 or Day 155 in Cohort B2 (End of study) post dose | — |
| Safety and tolerability of TE-8105 by the incidence of injection site reactions (ISRs) | SAD: On D 1, D 2, D 3, D 5, D 8. MAD Cohort B1: On D 1, D 2, D 3, D 8, D 15, D 29, D 43, D 57, D 64 post dose. MAD Cohort B2: On D 1, D2, D 3, D 5, D 8, D 15, D 29, D 43, D 57, D 71, D 85, D 99, D 113, D 117, D 120 and D 127 | — |
Secondary
| Measure | Time frame |
|---|---|
| PK Parameters : Time to maximum observed concentration (Tmax) | SAD: Predose and post dose on D1, D2, D3, D5, D8, D11, D15, D22, D29, D43 (EOS) |
| PK Parameters : Area under the concentration-time curve (AUC) from time zero to the last measurable concentration (AUC 0-last) | SAD: Predose and post dose on D1, D2, D3, D5, D8, D11, D15, D22, D29, D43 (EOS) |
| PK Parameters : Minimum observed concentration (Cmin) | MAD B1: Pre and post dose on D1, D2, D3, D8, D15, D29, D43, D57, D58, D59, D64, D71, D92, D113, D134; MAD B2: Pre and post dose on D1, D2, D3, D5, D8, D15, D29, D43, D57, D58, D71, D85, D99, D113, D114, D115, D117, D120, D127, D141 and D155 |
| PK Parameters : AUC over a dosing interval (AUCτ). | MAD B1: Pre and post dose on D1, D2, D3, D8, D15, D29, D43, D57, D58, D59, D64, D71, D92, D113, D134; MAD B2: Pre and post dose on D1, D2, D3, D5, D8, D15, D29, D43, D57, D58, D71, D85, D99, D113, D114, D115, D117, D120, D127, D141 and D155 |
| Number of participants with change in body weight from baseline with multiple doses of TE-8105. | Up to 20 weeks post first dose administration in MAD Cohort B1 and up to 23 weeks post first dose administration in MAD Cohort B2 |
| Number of participants with change in Body mass index (BMI) from baseline with multiple doses of TE-8105. | Up to 20 weeks post first dose administration in MAD Cohort B1 and up to 23 weeks post first dose administration in MAD Cohort B2 |
| PK Parameters : Maximum observed concentration (Cmax) | SAD: Predose and post dose on D1, D2, D3, D5, D8, D11, D15, D22, D29, D43 (EOS) |
Countries
Australia
Outcome results
None listed