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Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of KP104 to Treat Glomerulonephritis

Primary Purpose

Glomerulonephritis

Status
Not yet recruiting
Phase
Phase 2
Locations
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 Glomerulonephritis focused on measuring KP104, Immunoglobulin A Nephropathy, Compliment-mediated Glomerulonephritis, Complement Inhibitor

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Weight of >35 kilograms (kg) at Screening
  • Body mass index (BMI) of <35 kilograms per square meter (kg/m^2)
  • UPCR >1.5 grams per gram (g/g) by 24-hour urine collection at Screening
  • Documented diagnosis and clinical status of IgAN or C3G as follows:

IgAN:

  • Diagnosis of IgAN verified by biopsy taken within the past 12 months
  • On stable regimen of angiotensin converting enzyme or angiotensin blocking agents for 12 weeks and/or sodium-glucose cotransporter-2 (SGLT2) inhibitors for 6 weeks at Screening

C3G:

  • Diagnosis of C3G verified by biopsy taken within the past 12 months
  • On stable regimen of angiotensin converting enzyme or angiotensin blocking agents for 12 weeks and/or SGLT2 inhibitors for 6 weeks 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 1 day prior to dosing of study drug

Exclusion Criteria:

  • Any clinically significant, poorly controlled underlying illness other than IgAN or C3G, as determined by the investigator
  • Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibiotics, antivirals, or antifungals
  • History of infections with encapsulated organisms
  • History of untreated tuberculosis
  • 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)
  • eGFR <30 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  • Presence of crescent formation in >50 percent (%) of glomeruli assessed on renal biopsy
  • Nephrotic syndrome
  • Rapidly progressive glomerulonephritis, defined as a fall in eGFR of > 30 mL/min/1.73 m^2 within 24 weeks prior to the Screening Visit
  • Receiving renal replacement therapy or anticipated to require renal replacement therapy during the duration of the study

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    IgAN Cohort Stage 1 Dose 1

    C3G Cohort Stage 1 Dose 1

    IgAN Cohort Stage 1 Dose 2

    C3G Cohort Stage 1 Dose 2

    IgAN Cohort Stage 2

    C3G Cohort Stage 2

    Arm Description

    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 1. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 1. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 2. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 2. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.

    Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD.

    Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD.

    Outcomes

    Primary Outcome Measures

    Percent change from Baseline in 24-hour urinary protein creatinine ratio (UPCR) at Week 24 (C3G) for participants in Stage 2
    The UPCR will be calculated as percent change in protein (Pr)/ Creatinine (Cr).

    Secondary Outcome Measures

    Number of participants reporting Treatment-Emergent Adverse Events (TEAEs)
    An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. A TEAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment.
    Number of participants reporting Treatment-Emergent Serious Adverse Events (TESAEs)
    A TESAE is defined as a serious AE (SAE) that started or worsened in severity on or after the first dose of study treatment.
    Number of participants reporting AEs of Special Interest (AESIs)
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. Number of participants with AESIs including infections and local or systemic administration reactions will be assessed.
    Maximum concentration (Cmax) of KP104
    Blood samples will collected at indicated timepoints to assess Cmax.
    Trough concentration (Ctrough) of KP104 at steady state
    Blood samples will collected at indicated timepoints to assess Ctrough.
    Change from Baseline in estimated glomerular filtration rate (eGFR) at Week 24 (C3G) for participants in Stage 2

    Full Information

    First Posted
    August 24, 2022
    Last Updated
    August 9, 2023
    Sponsor
    Kira Pharmacenticals (US), LLC.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05517980
    Brief Title
    Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of KP104 to Treat Glomerulonephritis
    Official Title
    An Open-label, Phase 2 Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of KP104 in Subjects With IgA Nephropathy (IgAN) and Complement 3 Glomerulopathy (C3G)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 2023 (Anticipated)
    Primary Completion Date
    September 2025 (Anticipated)
    Study Completion Date
    September 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 efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of KP104 in participants with IgAN and C3G. The study will start with enrolling the IgAN cohort. Approximately 42 participants with IgAN will be enrolled in 2 stages: Stage 1 will be used to collect safety, immunogenicity, PK, and PD data to select the optimal biologic dose (OBD) of KP104 for IgAN, as well as to preliminarily explore the effect of KP104 on C3G. Stage 2 will be used to collect safety, immunogenicity, PK, PD, and efficacy data at the OBD dose of KP104 for IgAN and C3G. As soon as the OBD for IgAN is determined, eligible participants with C3G will be enrolled and dosed at the OBD for IgAN for a minimum of 48 weeks for weekly maintenance dosing and a minimum of 47 weeks for biweekly maintenance dosing. Approximately 10 participants with C3G will be enrolled.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Glomerulonephritis
    Keywords
    KP104, Immunoglobulin A Nephropathy, Compliment-mediated Glomerulonephritis, Complement Inhibitor

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    IgAN Cohort Stage 1 Dose 1
    Arm Type
    Experimental
    Arm Description
    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 1. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.
    Arm Title
    C3G Cohort Stage 1 Dose 1
    Arm Type
    Experimental
    Arm Description
    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 1. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.
    Arm Title
    IgAN Cohort Stage 1 Dose 2
    Arm Type
    Experimental
    Arm Description
    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 2. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.
    Arm Title
    C3G Cohort Stage 1 Dose 2
    Arm Type
    Experimental
    Arm Description
    Participants will be randomized to receive weekly or biweekly maintenance doses of KP104 at Dose 2. Participants in Stage 1 will also have the opportunity to be switched to the OBD if they are still in the treatment period.
    Arm Title
    IgAN Cohort Stage 2
    Arm Type
    Experimental
    Arm Description
    Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD.
    Arm Title
    C3G Cohort Stage 2
    Arm Type
    Experimental
    Arm Description
    Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD.
    Intervention Type
    Drug
    Intervention Name(s)
    KP104
    Intervention Description
    Participants will receive loading and/or weekly maintenance subcutaneous (SC) doses of KP104.
    Primary Outcome Measure Information:
    Title
    Percent change from Baseline in 24-hour urinary protein creatinine ratio (UPCR) at Week 24 (C3G) for participants in Stage 2
    Description
    The UPCR will be calculated as percent change in protein (Pr)/ Creatinine (Cr).
    Time Frame
    Baseline and at Week 24
    Secondary Outcome Measure Information:
    Title
    Number of participants reporting Treatment-Emergent Adverse Events (TEAEs)
    Description
    An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. A TEAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment.
    Time Frame
    Up to 56 Weeks
    Title
    Number of participants reporting Treatment-Emergent Serious Adverse Events (TESAEs)
    Description
    A TESAE is defined as a serious AE (SAE) that started or worsened in severity on or after the first dose of study treatment.
    Time Frame
    Up to 56 Weeks
    Title
    Number of participants reporting AEs of Special Interest (AESIs)
    Description
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. Number of participants with AESIs including infections and local or systemic administration reactions will be assessed.
    Time Frame
    Up to 56 Weeks
    Title
    Maximum concentration (Cmax) of KP104
    Description
    Blood samples will collected at indicated timepoints to assess Cmax.
    Time Frame
    At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395
    Title
    Trough concentration (Ctrough) of KP104 at steady state
    Description
    Blood samples will collected at indicated timepoints to assess Ctrough.
    Time Frame
    At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395
    Title
    Change from Baseline in estimated glomerular filtration rate (eGFR) at Week 24 (C3G) for participants in Stage 2
    Time Frame
    Baseline and at Week 24

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Weight of >35 kilograms (kg) at Screening Body mass index (BMI) of <35 kilograms per square meter (kg/m^2) UPCR >1.0 grams per gram (g/g) by 24-hour urine collection at Screening Documented diagnosis and clinical status of IgAN or C3G as follows: IgAN: Diagnosis of IgAN verified by biopsy taken within the past 3 years prior to enrolment. On stable regimen of angiotensin converting enzyme or angiotensin blocking agents for 12 weeks and/or sodium-glucose cotransporter-2 (SGLT2) inhibitors for 6 weeks at Screening C3G: Diagnosis of C3G verified by biopsy taken within the past 3 years prior to enrolment. On stable regimen of angiotensin converting enzyme or angiotensin blocking agents for 12 weeks and/or SGLT2 inhibitors for 6 weeks 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 1 day prior to dosing of study drug Exclusion Criteria: Any clinically significant, poorly controlled underlying illness other than IgAN or C3G, as determined by the investigator Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibiotics, antivirals, or antifungals History of infections with encapsulated organisms History of untreated tuberculosis 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) eGFR <30 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula Presence of crescent formation in >50 percent (%) of glomeruli assessed on renal biopsy Nephrotic syndrome defined as presence of substantial proteinuria (> 3.5 g/24 hours), hypoalbuminemia (< 30 grams per liter [g/L]), and edema/hyperlipidemia. Nephrotic range proteinuria alone is acceptable. Rapidly progressive glomerulonephritis, defined as a fall in eGFR of > 30 mL/min/1.73 m^2 within 24 weeks prior to the Screening Visit Receiving renal replacement therapy or anticipated to require renal replacement therapy during the duration of the study NOTE: 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

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes

    Learn more about this trial

    Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of KP104 to Treat Glomerulonephritis

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