The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in complement inhibitor-naïve participants with PNH. The study will be conducted in 2 parts. Part 1 is a dose-selection study to assess escalating doses and varying dose intervals of KP104. Part 2 is a proof-of-concept (POC) study assessing the efficacy of the optimal intravenous (IV) loading dose followed by the optimal maintenance dose and regimen of KP104. Participants who complete the Initial Treatment Period and demonstrate benefit from KP104 will be eligible for a 9-month open-label extension (OLE) treatment period.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.
Peking Union Medical College Hospital
Beijing, China
Jiangsu Province Hospital
Nanjing, China
Chinese Academy of Medical Sciences Peking Union Medical College - Institute of Hematology Blood Diseases Hospital
Tianjin, China
Henan Cancer Hospital
Zhengzhou, China
Part 1: 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.
Time frame: Up to Week 4
Part 2: Percentage of participants with >= 2 grams per deciliter (g/dL) increase in hemoglobin level from Baseline in the absence of transfusion for weekly dosing
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Time frame: Baseline and at Week 12
Part 2: Percentage of participants with >= 2 g/dL increase in hemoglobin level from Baseline in the absence of transfusion for biweekly dosing
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Time frame: Baseline and at Week 13
Open-label Extension (OLE): Number of participants reporting Treatment Emergent Adverse Events (TEAEs), treatment-emergent serious adverse events (TESAEs) and AEs of special interest (AESIs)
Time frame: Up to 9 months
Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing
Blood samples will be collected for the analysis of serum LDH.
Time frame: Baseline and at Week 12
Part 2: Change from Baseline in serum LDH levels for biweekly dosing
Blood samples will be collected for the analysis of serum LDH.
Time frame: Baseline and at Week 13
Part 2: Change from Baseline in hemoglobin level for weekly dosing
Blood samples will be collected for the analysis of hemoglobin level
Time frame: Baseline and at Week 12
Part 2: Change from Baseline in the hemoglobin level for biweekly dosing
Blood samples will be collected for the analysis of hemoglobin level.
Time frame: Baseline and at Week 13
Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing
The RBC transfusion dependence is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Time frame: Baseline and at Week 12
Part 2: Change in RBC transfusion dependence for biweekly dosing
The RBC transfusion difference is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Time frame: Baseline and at Week 13
Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs
Time frame: Up to Week 13
Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104
Time frame: Up to Week 13
Part 1 and 2: Trough concentration (Ctrough) of KP104
Time frame: Up to Week 13
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.