Clinical trial NCT05476887: To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104
Official title: An Open-label, Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104 in Complement Inhibitor-naïve Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: KP104
Paroxysmal nocturnal hemoglobinuria
Complement Inhibitor
Dose Selection
Proof of Concept
Lead sponsor: Kira Pharmacenticals (US), LLC.
Sponsor class: INDUSTRY
First posted: 2022-07-27
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

Initial Treatment Period:

* 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 × upper limit of normal (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.

Extension Treatment Period (OLE):

* Complete the 12-week (weekly dosing) or 13-week (biweekly dosing) Initial Treatment Period per the protocol.
* Benefited from KP104 treatment and will continue benefiting from KP104 treatment per the investigator's judgement.
* Willing to participate in Extension Treatment Period, able to comply with this protocol and be available for the entire duration of the study.

Exclusion Criteria:

Initial Treatment Period:

* 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.

Extension Treatment Period (OLE):

* Women who are pregnant.
* Women of childbearing potential and men with sexual partners of childbearing potential who are not using adequate contraception and who are not willing to use adequate contraception.
* Any medical condition that, in the opinion of the investigator, may pose a safety risk to a participant in this study, or may interfere with study participation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Part 1: Number of participants with Dose-limiting toxicities (DLT)
timeFrame: Up to Week 4
measure: 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
timeFrame: Baseline and at Week 12
measure: Part 2: Percentage of participants with >= 2 g/dL increase in hemoglobin level from Baseline in the absence of transfusion for biweekly dosing
timeFrame: Baseline and at Week 13
measure: 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)
timeFrame: Up to 9 months
Secondary outcomes:
measure: Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing
timeFrame: Baseline and at Week 12
measure: Part 2: Change from Baseline in serum LDH levels for biweekly dosing
timeFrame: Baseline and at Week 13
measure: Part 2: Change from Baseline in hemoglobin level for weekly dosing
timeFrame: Baseline and at Week 12
measure: Part 2: Change from Baseline in the hemoglobin level for biweekly dosing
timeFrame: Baseline and at Week 13
measure: Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing
timeFrame: Baseline and at Week 12
measure: Part 2: Change in RBC transfusion dependence for biweekly dosing
timeFrame: Baseline and at Week 13
measure: Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs
timeFrame: Up to Week 13
measure: Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104
timeFrame: Up to Week 13
measure: Part 1 and 2: Trough concentration (Ctrough) of KP104
timeFrame: Up to Week 13
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Tianjin
country: China
facility: Chinese Academy of Medical Sciences Peking Union Medical College - Institute of Hematology Blood Diseases Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
References: