Účinnost, bezpečnost, farmakokinetika a farmakodynamika KP104 k léčbě glomerulonefritidy
Otevřená studie fáze 2 k vyhodnocení účinnosti, bezpečnosti, farmakokinetiky a farmakodynamiky KP104 u pacientů s IgA nefropatií (IgAN) a glomerulopatií komplementu 3 (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.
Přehled studie
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Study Director
- Telefonní číslo: 650-549-1400
- E-mail: privacy@kirapharma.com
Studijní místa
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Beijing, Čína
- Nábor
- Peking University First Hospital
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Kontakt:
- Investigative Site #1
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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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Experimentální: 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. |
|
Experimentální: 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. |
|
Experimentální: 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. |
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Experimentální: 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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Experimentální: 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. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Změna odhadované rychlosti glomerulární filtrace (eGFR) od výchozí hodnoty ve 24. týdnu (C3G) pro účastníky ve fázi 2
Časové okno: Výchozí stav a v týdnu 24
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Výchozí stav a v týdnu 24
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Number of participants reporting Treatment-Emergent Adverse Events (TEAEs)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- KP104-203
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