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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])
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A SAD Cohort 1 | Experimental | Each participant will receive TE-8105 administered by subcutaneous injection. |
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| Part A SAD Cohort 2 | Experimental | Each participant will receive TE-8105 administered by subcutaneous injection. |
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| Part A SAD Cohort 3 | Experimental | Each participant will receive TE-8105 administered by subcutaneous injection. |
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| Part A SAD Cohort 4 | Experimental | Each participant will receive TE-8105 administered by subcutaneous injection. |
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| Part A SAD Cohort 5 (Adaptive Cohort) | Experimental | Each participant will receive TE-8105 administered by subcuteneous injection. |
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| Part B MAD Cohort 1 | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TE-8105 SAD Cohort 1 | Drug | 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Number of participants with change in serum blood parameters | Laboratory assessment includes Hematology, coagulation and serum chemistry. | 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 |
| Number of participants with change in urine parameters | Laboratory assessment includes urinalysis | 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 |
| Number of participants with changes in the physical examination findings | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| PK Parameters : Maximum observed concentration (Cmax) | SAD: Predose and post dose on D1, D2, D3, D5, D8, D11, D15, D22, D29, D43 (EOS) | |
| PK Parameters : Maximum observed concentration (Cmax) | 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 |
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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:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CMAX Clinical Research | Adelaide | South Australia | 5000 | Australia |
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Each participant will receive TE-8105 administered by subcutaneous injection. |
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| Part B MAD Cohort 2 | Experimental | Each participant will receive TE-8105 administered by subcutaneous injection. |
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| TE-8105 SAD Cohort 3 | Drug | 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. |
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| TE-8105 SAD Cohort 5 (Adaptive cohort) | Drug | 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. |
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| TE-8105 MAD Cohort 1 | Drug | 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. |
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| TE-8105 MAD Cohort 2 | Drug | 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) |
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| TE-8105 SAD Cohort 2 | Drug | Each participant will receive one dose of TE-8105 0.75mg injection via subcutaneous (SC) injection into the abdomen on Day 1. |
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| TE-8105 SAD Cohort 4 | Drug | 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. |
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| Number of participants with changes in 12 lead ECG findings | ECG measurements to include Heart rate, PR, QRS, QT, and QTcF intervals. | 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 |
| 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) | Systolic and diastolic BP will be measured | 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 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 |
| 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 |
| 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 : Time to maximum observed concentration (Tmax) | 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 : 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 : Area under the concentration-time curve (AUC) from time zero to the last measurable concentration (AUC 0-last) | 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 : 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 (AUCĪ). | 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 |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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