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NCT Number: NCT05476887

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

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.

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Key information

Conditions

Paroxysmal Nocturnal Hemoglobinuria Anemia Anemia, Hemolytic Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinuria, Paroxysmal Myelodysplastic Syndromes

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Peking Union Medical College Hospital, Beijing, China

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

KP104

Drug

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

Primary outcomes

  1. Part 1: Number of participants with Dose-limiting toxicities (DLT)

    Time frame: Up to Week 4

    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.

  2. 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

    Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.

  3. 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

    Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.

  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

Secondary outcomes

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

    Time frame: Baseline and at Week 12

    Blood samples will be collected for the analysis of serum LDH.

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

    Time frame: Baseline and at Week 13

    Blood samples will be collected for the analysis of serum LDH.

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

    Time frame: Baseline and at Week 12

    Blood samples will be collected for the analysis of hemoglobin level

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

    Time frame: Baseline and at Week 13

    Blood samples will be collected for the analysis of hemoglobin level.

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

    Time frame: Baseline and at Week 12

    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.

  6. Part 2: Change in RBC transfusion dependence for biweekly dosing

    Time frame: Baseline and at Week 13

    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.

  7. Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs

    Time frame: Up to Week 13

  8. Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104

    Time frame: Up to Week 13

  9. Part 1 and 2: Trough concentration (Ctrough) of KP104

    Time frame: Up to Week 13

Sponsors and collaborators

Lead sponsor

Kira Pharmacenticals (US), LLC.

Industry

Registry information

Official study 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)

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Jul 27, 2022
Registry last updated
Oct 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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