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

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
KP104
Sponsored by
Kira Pharmacenticals (US), LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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)

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.
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.
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)

Secondary Outcome Measures

Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing
Blood samples will be collected for the analysis of serum LDH.
Part 2: Change from Baseline in serum LDH levels for biweekly dosing
Blood samples will be collected for the analysis of serum LDH.
Part 2: Change from Baseline in hemoglobin level for weekly dosing
Blood samples will be collected for the analysis of hemoglobin level
Part 2: Change from Baseline in the hemoglobin level for biweekly dosing
Blood samples will be collected for the analysis of hemoglobin level.
Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing
The RBC transfusion dependence is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Part 2: Change in RBC transfusion dependence for biweekly dosing
The RBC transfusion difference is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs
Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104
Part 1 and 2: Trough concentration (Ctrough) of KP104

Full Information

First Posted
July 25, 2022
Last Updated
March 6, 2023
Sponsor
Kira Pharmacenticals (US), LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT05476887
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 25, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kira Pharmacenticals (US), LLC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria
Keywords
KP104, Paroxysmal nocturnal hemoglobinuria, Complement Inhibitor, Dose Selection, Proof of Concept

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose escalation Cohort 1
Arm Type
Experimental
Arm Description
Participants will receive escalating and varying dose intervals of KP104 every week.
Arm Title
Part 1: Dose escalation Cohort 2
Arm Type
Experimental
Arm Description
Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.
Arm Title
Part 1: Dose escalation Cohort 3
Arm Type
Experimental
Arm Description
Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.
Arm Title
Part 2: Proof-of-concept Cohort 1
Arm Type
Experimental
Arm Description
Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly.
Arm Title
Open-label extension (OLE)
Arm Type
Experimental
Arm Description
Participants will receive KP104, who benefit from KP104 treatment in Part 1 and 2
Intervention Type
Drug
Intervention Name(s)
KP104
Intervention Description
KP104 intravenously (IV loading + subcutaneous [SC] maintenance every week [QW] or every 2 weeks [Q2W]) will be administered.
Primary Outcome Measure Information:
Title
Part 1: Number of participants with Dose-limiting toxicities (DLT)
Description
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.
Time Frame
Up to Week 4
Title
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
Description
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Time Frame
Baseline and at Week 12
Title
Part 2: Percentage of participants with >= 2 g/dL increase in hemoglobin level from Baseline in the absence of transfusion for biweekly dosing
Description
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Time Frame
Baseline and at Week 13
Title
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
Secondary Outcome Measure Information:
Title
Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing
Description
Blood samples will be collected for the analysis of serum LDH.
Time Frame
Baseline and at Week 12
Title
Part 2: Change from Baseline in serum LDH levels for biweekly dosing
Description
Blood samples will be collected for the analysis of serum LDH.
Time Frame
Baseline and at Week 13
Title
Part 2: Change from Baseline in hemoglobin level for weekly dosing
Description
Blood samples will be collected for the analysis of hemoglobin level
Time Frame
Baseline and at Week 12
Title
Part 2: Change from Baseline in the hemoglobin level for biweekly dosing
Description
Blood samples will be collected for the analysis of hemoglobin level.
Time Frame
Baseline and at Week 13
Title
Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing
Description
The RBC transfusion dependence is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Time Frame
Baseline and at Week 12
Title
Part 2: Change in RBC transfusion dependence for biweekly dosing
Description
The RBC transfusion difference is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Time Frame
Baseline and at Week 13
Title
Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs
Time Frame
Up to Week 13
Title
Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104
Time Frame
Up to Week 13
Title
Part 1 and 2: Trough concentration (Ctrough) of KP104
Time Frame
Up to Week 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director
Email
privacy@kirapharma.com
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Name
Jiangsu Province Hospital
City
Nanjing
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Chinese Academy of Medical Sciences Peking Union Medical College - Institute of Hematology Blood Diseases Hospital
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Name
Henan Cancer Hospital
City
Zhengzhou
Country
China
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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