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

• Register: ClinicalTrials.gov
• Last refreshed on: 4 November 2024
• Main ID: NCT05476887
• Date of registration: 25/07/2022
• Prospective Registration: Yes
• Primary sponsor: Kira Pharmacenticals (US), LLC.
• Public title: To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104
• Scientific 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)
• Date of first enrolment: November 25, 2022
• Target sample size: 35
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05476887
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

China

Key inclusion & exclusion 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.


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria

Intervention(s)

Drug: KP104

Primary Outcome(s)

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 [Time Frame: Baseline and at Week 12]

Part 1: Number of participants with Dose-limiting toxicities (DLT) [Time Frame: Up to Week 4]

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: Percentage of participants with >= 2 g/dL increase in hemoglobin level from Baseline in the absence of transfusion for biweekly dosing [Time Frame: Baseline and at Week 13]

Secondary Outcome(s)

Part 2: Change from Baseline in the hemoglobin level for biweekly dosing [Time Frame: Baseline and at Week 13]

Part 2: Change in RBC transfusion dependence for biweekly dosing [Time Frame: Baseline and at Week 13]

Part 2: Change from Baseline in serum LDH levels for biweekly dosing [Time Frame: Baseline and at Week 13]

Part 2: Change from Baseline in hemoglobin level for weekly dosing [Time Frame: Baseline and at Week 12]

Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs [Time Frame: Up to Week 13]

Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing [Time Frame: Baseline and at Week 12]

Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing [Time Frame: Baseline and at Week 12]

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]

Secondary ID(s)

KP104-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors