Wirksamkeit, Sicherheit, Pharmakokinetik und Pharmakodynamik von KP104 zur Behandlung von Glomerulonephritis
Eine offene Phase-2-Studie zur Bewertung der Wirksamkeit, Sicherheit, Pharmakokinetik und Pharmakodynamik von KP104 bei Patienten mit IgA-Nephropathie (IgAN) und Komplement-3-Glomerulopathie (C3G)
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.
Studienübersicht
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
Kontakte und Standorte
Studienkontakt
- Name: Study Director
- Telefonnummer: 650-549-1400
- E-Mail: privacy@kirapharma.com
Studienorte
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Beijing, China
- Rekrutierung
- Peking University First Hospital
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Kontakt:
- Investigative Site #1
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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:
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Diagnosis of C3G verified by biopsy taken within the past 3 years prior to enrolment.
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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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Sequenzielle Zuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: IgAN Cohort Stage 1 Dose 1
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 receive loading and/or weekly maintenance subcutaneous (SC) doses of KP104. |
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Experimental: C3G Cohort Stage 1 Dose 1
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 receive loading and/or weekly maintenance subcutaneous (SC) doses of KP104. |
|
Experimental: IgAN Cohort Stage 1 Dose 2
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 loading and/or weekly maintenance subcutaneous (SC) doses of KP104. |
|
Experimental: C3G Cohort Stage 1 Dose 2
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 loading and/or weekly maintenance subcutaneous (SC) doses of KP104. |
|
Experimental: IgAN Cohort Stage 2
Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD. |
Participants will receive loading and/or weekly maintenance subcutaneous (SC) doses of KP104. |
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Experimental: C3G Cohort Stage 2
Participants will receive weekly or biweekly maintenance doses of KP104 at the OBD. |
Participants will receive loading and/or weekly maintenance subcutaneous (SC) doses of KP104. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Percent change from Baseline in 24-hour urinary protein creatinine ratio (UPCR) at Week 24 (C3G) for participants in Stage 2
Zeitfenster: Baseline and at Week 24
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The UPCR will be calculated as percent change in protein (Pr)/ Creatinine (Cr). |
Baseline and at Week 24
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Änderung der geschätzten glomerulären Filtrationsrate (eGFR) gegenüber dem Ausgangswert in Woche 24 (C3G) für Teilnehmer in Stufe 2
Zeitfenster: Ausgangswert und in Woche 24
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Ausgangswert und in Woche 24
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Number of participants reporting Treatment-Emergent Adverse Events (TEAEs)
Zeitfenster: Up to 56 Weeks
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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. |
Up to 56 Weeks
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Number of participants reporting Treatment-Emergent Serious Adverse Events (TESAEs)
Zeitfenster: Up to 56 Weeks
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A TESAE is defined as a serious AE (SAE) that started or worsened in severity on or after the first dose of study treatment. |
Up to 56 Weeks
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Number of participants reporting AEs of Special Interest (AESIs)
Zeitfenster: Up to 56 Weeks
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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. |
Up to 56 Weeks
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Maximum concentration (Cmax) of KP104
Zeitfenster: At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395
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Blood samples will collected at indicated timepoints to assess Cmax. |
At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395
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Trough concentration (Ctrough) of KP104 at steady state
Zeitfenster: At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395
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Blood samples will collected at indicated timepoints to assess Ctrough. |
At Baseline (Day 1), Days 8, 15, 22, 29, 43, 57, 85, 169, 253, 337, 365 and 395
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Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Männliche Urogenitalerkrankungen
- Nierenerkrankungen
- Urologische Erkrankungen
- Weibliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Autoimmunerkrankungen
- Erkrankungen des Immunsystems
- Nephritis
- Glomerulonephritis
- Glomerulonephritis, IGA
Andere Studien-ID-Nummern
- KP104-203
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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