To Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Single and Multiple Doses of KP104

Study Overview
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Brief Summary
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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).

Official Title
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SYNERGY-1: A Phase 1 First-in-human, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Single and Multiple Doses of KP104 in Healthy Subjects

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: KP104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight of > 40 kilograms (kg) and < 120 kg at Screening. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead ECG, clinical laboratory findings, and vital signs at Screening and Check-in. Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the normal range at the Screening Visit; participants with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities. Creatinine clearance based on the Cockcroft-Gault equation of >= 80 milliliters per minute (ml/min). Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the end of study (EOS) visit. Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone to confirm post-menopausal status. Exclusion Criteria: Any clinically significant underlying illness in the opinion of the Investigator. Any history or sign of significant chronic active or recurrent infection, or screening laboratory evidence consistent with a significant chronic active or recurrent infection requiring treatment with antibacterials, antivirals, or antifungals. Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibacterials, antivirals, or antifungals. History of clinically significant hematologic or bone marrow disease or blood dyscrasias. History of meningococcal infection. History of tuberculosis. History of asplenia (functional or anatomical). Prior exposure to KP104. Known allergy to penicillin antibiotics or history of allergy or contraindication to required prophylactic antibiotic therapy to be used during the study. Known or suspected complement deficiency during screening. Positive serology for Hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at Screening. History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Check-in. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Single Ascending Dose Cohort 1<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 1: Single Ascending Dose Cohort 2<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 1: Single Ascending Dose Cohort 3<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 1: Single Ascending Dose Cohort 4<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 1: Single Ascending Dose Cohort 5<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 1: Single Ascending Dose Cohort 6<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 1: Single Ascending Dose Cohort 7<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 2: Multiple Ascending Dose Cohort 1<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 2: Multiple Ascending Dose Cohort 2<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Experimental: Part 2: Multiple Ascending Dose Cohort 3<br> | Drug: KP104<br>* Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.<br>|
| Placebo Comparator: Part 1: Placebo<br> | Drug: Placebo<br>* Participants will receive matching placebo which is KP104 vehicle containing sodium phosphate, sodium chloride, and L-Lysine Hydrochloride (L-Lys-HCL).<br>|
| Placebo Comparator: Part 2: Placebo<br> | Drug: Placebo<br>* Participants will receive matching placebo which is KP104 vehicle containing sodium phosphate, sodium chloride, and L-Lysine Hydrochloride (L-Lys-HCL).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 |  | Baseline and up to Day 29 | 
| Change from baseline in rabbit red blood cell (RBC) assay |  | Baseline and up to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy participants, KP104, Single ascending Dose, Paroxysmal Nocturnal Hemoglobinuria, Multiple Ascending Dose, First in Human, Complement Inhibitor