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The purpose of this study is to evaluate safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in healthy volunteers. The study will be conducted in 2 parts: Part 1, the single ascending dose (SAD) is the first in human (FIH) study of KP104 and Part 2, multiple ascending dose (MAD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Single Ascending Dose Cohort 1 | Experimental |
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| Part 1: Single Ascending Dose Cohort 2 | Experimental |
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| Part 1: Single Ascending Dose Cohort 3 | Experimental |
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| Part 1: Single Ascending Dose Cohort 4 | Experimental |
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| Part 1: Single Ascending Dose Cohort 5 | Experimental |
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| Part 1: Single Ascending Dose Cohort 6 | Experimental |
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| Part 1: Single Ascending Dose Cohort 7 | Experimental |
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| Part 2: Multiple Ascending Dose Cohort 1 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KP104 | Drug | Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of participants reporting Treatment Emergent Adverse Events (TEAEs) | An Adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. A TEAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment. | Up to Day 85 |
| Number of participants reporting Treatment Emergent Serious Adverse Events (TESAEs) | A TESAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment. | Up to Day 85 |
| Number of participants with Dose-limiting toxicities (DLT) | A DLT is defined as any adverse event considered by the investigator to be KP104-related with a severity greater than or equal to (>=) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 which also represents a shift from baseline clinical status of > 1 NCI CTCAE grade. A hypersensitivity/administration reaction occurring with a severity of Grade 2 despite the use of pre-medications will also be designated as a DLT. | Up to Day 85 |
| Number of participants reporting AEs of Special interests (AESIs) | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. Number of participants with AESIs including infections and local or systemic administration reactions will be assessed. | Up to Day 85 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum concentration (Cmax) of KP104 | Up to Day 29 | |
| Area under the concentration-time profile (AUC) of KP104 | Up to Day 29 | |
| Change from baseline in total and free serum C5 levels |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in serum free C5 levels to Minimum concentration (Cmin) correlation | Baseline and up to Day 29 | |
| Changes in serum free C5 levels to AUC correlation | Baseline and up to Day 29 | |
Inclusion Criteria:
Exclusion Criteria:
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CMAX Clinical Research | Adelaide | Australia |
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| ID | Term |
|---|---|
| D006457 | Hemoglobinuria, Paroxysmal |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Experimental |
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| Part 2: Multiple Ascending Dose Cohort 2 | Experimental |
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| Part 2: Multiple Ascending Dose Cohort 3 | Experimental |
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| Part 1: Placebo | Placebo Comparator |
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| Part 2: Placebo | Placebo Comparator |
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| Placebo | Drug | Participants will receive matching placebo which is KP104 vehicle containing sodium phosphate, sodium chloride, and L-Lysine Hydrochloride (L-Lys-HCL). |
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| Baseline and up to Day 29 |
| Change from baseline in rabbit red blood cell (RBC) assay | Baseline and up to Day 29 |
| Changes in C3b activity to Cmax correlation |
| Baseline and up to Day 29 |
| Changes in C3b activity to Cmin correlation | Baseline and up to Day 29 |
| Changes in C3b activity to AUC correlation | Baseline and up to Day 29 |
| Changes in rabbit RBC lysis to Cmax correlation | Baseline and up to Day 29 |
| Changes in rabbit RBC lysis to Cmin correlation | Baseline and up to Day 29 |
| Changes in rabbit RBC lysis to AUC correlation | Baseline and up to Day 29 |
| Immunogenicity of KP104 | Up to Day 29 |
| Maximum tolerated dose (MTD) of KP104 | Up to Day 29 |
| Optimal biologic dose (OBD) of KP104 | Up to Day 29 |
| Number of participants with clinically significant changes in laboratory values, electrocardiograms (ECGs), physical examinations, and vital signs | Up to Day 29 |
| Changes in serum free complement component C5 levels to Cmax correlation | Baseline and up to Day 29 |
| Dose optimization of KP104 | Up to Day 29 |
| Systemic clearance (Cl) of KP104 | Up to Day 29 |
| Elimination half-life (t½) of KP104 | Up to Day 29 |
| Change from baseline in complement component of C3b activity assay | Baseline and up to Day 29 |
| Absolute bioavailability of KP104 administered SC (F) | Up to Day 29 |
| Change from baseline in Factor H (FH) serum levels | Baseline and up to Day 29 |
| D009190 |
| Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |