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

NCT05476887 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: KP104-201
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

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

Keywords

KP104; Paroxysmal nocturnal hemoglobinuria; Complement Inhibitor; Dose Selection; Proof of Concept

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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)

  Up to 9 months

Secondary Outcomes (9)

• Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing

  Baseline and at Week 12

• Part 2: Change from Baseline in serum LDH levels for biweekly dosing

  Baseline and at Week 13

• Part 2: Change from Baseline in hemoglobin level for weekly dosing

  Baseline and at Week 12

• Part 2: Change from Baseline in the hemoglobin level for biweekly dosing

  Baseline and at Week 13

• Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing

  Baseline and at Week 12

Study Arms (5)

Part 1: Dose escalation Cohort 1

EXPERIMENTAL

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

Drug: KP104

Part 1: Dose escalation Cohort 2

EXPERIMENTAL

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

Drug: KP104

Part 1: Dose escalation Cohort 3

EXPERIMENTAL

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

Drug: KP104

Part 2: Proof-of-concept Cohort 1

EXPERIMENTAL

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

Drug: KP104

Open-label extension (OLE)

EXPERIMENTAL

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

Drug: KP104

Interventions

KP104 DRUG

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

Open-label extension (OLE); 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kira Pharmacenticals (US), LLC.: lead

Study Sites (4)

Peking Union Medical College Hospital

Beijing, China

Location

Jiangsu Province Hospital

Nanjing, China

Location

Chinese Academy of Medical Sciences Peking Union Medical College - Institute of Hematology Blood Diseases Hospital

Tianjin, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: July 27, 2022
• Study Start: November 25, 2022
• Primary Completion: November 1, 2024
• Study Completion: February 1, 2025
• Last Updated: October 28, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (4)