To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104

NCT ID: NCT05476887

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-25
• Study Completion Date: 2025-02-28

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose escalation Cohort 1

Participants will receive escalating and varying dose intervals of KP104 every week.

Group Type: EXPERIMENTAL

KP104

Intervention Type: DRUG

KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.

Part 1: Dose escalation Cohort 2

Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.

Group Type: EXPERIMENTAL

KP104

Intervention Type: DRUG

KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.

Part 1: Dose escalation Cohort 3

Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.

Group Type: EXPERIMENTAL

KP104

Intervention Type: DRUG

KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.

Part 2: Proof-of-concept Cohort 1

Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.

Group Type: EXPERIMENTAL

KP104

Intervention Type: DRUG

KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.

Open-label extension (OLE)

Participants will receive KP104, who benefit from KP104 treatment in Part 1 and 2

Group Type: EXPERIMENTAL

KP104

Intervention Type: DRUG

KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.

Interventions

KP104

KP104 intravenously (IV loading + subcutaneous \[SC\] maintenance every week \[QW\] or every 2 weeks \[Q2W\]) will be administered.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kira Pharmacenticals (US), LLC.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Countries

China

Other Identifiers

KP104-201

Identifier Type: -

Identifier Source: org_study_id