To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104
Paroxysmal Nocturnal Hemoglobinuria
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring KP104, Paroxysmal nocturnal hemoglobinuria, Complement Inhibitor, Dose Selection, Proof of Concept
Eligibility Criteria
Inclusion Criteria:
- Documented diagnosis of PNH confirmed by flow cytometry evaluation of white blood cells and red blood cells, with granulocyte or monocyte clone size of >= 10 percent (%) within 6 months of the Screening visit.
- Presence of 1 or more PNH-related signs or symptoms within 3 months of initiation of Screening.
- LDH >= 2.0 × ULN at screening.
- Hemoglobin <= 10.0 g/dL at screening.
- 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.
Exclusion Criteria:
- Any clinically significant poorly controlled underlying illness other than PNH per discretion of investigators.
- Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibiotics, antivirals, or antifungals.
- History of meningococcal infection.
- History of untreated tuberculosis.
- History of splenectomy
- Positive serology for Hepatitis C Virus (HCV) ribonucleic acid (RNA) or human immunodeficiency virus (HIV) at Screening
- History of bone marrow or stem cell transplantation
- Absolute neutrophil count (ANC) <500 cells per microliter (cells/μL)
- Reticulocyte count< 100 x 10^3 cells/μL
- Platelet count< 30,000 cells/μL
- History of systemic autoimmune disease
- Estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 meter square (mL/min/1.73 m^2) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Sites / Locations
- Peking Union Medical College HospitalRecruiting
- Jiangsu Province Hospital
- Chinese Academy of Medical Sciences Peking Union Medical College - Institute of Hematology Blood Diseases HospitalRecruiting
- Henan Cancer Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Part 1: Dose escalation Cohort 1
Part 1: Dose escalation Cohort 2
Part 1: Dose escalation Cohort 3
Part 2: Proof-of-concept Cohort 1
Open-label extension (OLE)
Participants will receive escalating and varying dose intervals of KP104 every week.
Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.
Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.
Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.
Participants will receive KP104, who benefit from KP104 treatment in Part 1 and 2