This study is the first time the new medicine CPV-104 is being tested in people. CPV-104 is designed to regulate the complement system, which can be overactive in diseases such as C3 glomerulopathy (C3G), an ultra-rare kidney disorder. The study includes healthy adults and adult patients with C3G to assess safety, tolerability, how the body processes the medicine, and whether the immune system reacts to it. The study is divided in two part; in Part 1 (SAD), healthy volunteers receive one IV dose of CPV-104 or a placebo while in Part 2 (MAD) patients with C3G receive four weekly IV doses of CPV-104 (no placebo). Participants will have close monitoring, including side-effect checks, blood and urine tests, ECGs, vital signs, and blood samples to measure drug levels and antibodies. For those with C3G, researchers will also observe kidney function, although the main goal is safety, not testing effectiveness. A Safety Review Committee will regularly review results to ensure it is safe to continue to the next dose or study group.
CPV-104-101 is a phase 1, first-in-human, dose-escalation, prospective trial, which will be conducted in two parts: Part 1 (Single Ascending Dose with healthy volunteers - SAD-HV) and Part 2 (Multiple Ascending Dose with C3G patients - MAD-C3G). Part 1 is double-blind, randomized, and placebo-controlled, while Part 2 is open-label and single-arm (CPV-104 only). Following a screening period, 21 healthy volunteers who meet the eligibility criteria will be assigned to one of four cohorts in SAD-HV Part 1. Three healthy volunteers will be assigned to Cohort 1 within SAD-HV Part 1 to receive a single dose of CPV-104. After completion of Cohort 1, 18 healthy volunteers will be randomly allocated within SAD-HV Cohorts 2, 3, and 4 to receive a single dose of either CPV-104 or placebo. After completion of SAD-HV Part 1, 18 C3G patients will be allocated within MAD-C3G Cohorts 5, 6, and 7 to receive four doses of CPV-104. All treatments will be administered intravenously by a healthcare professional (HCP). Before dosing in Cohorts 2, 3, 4, 5, 6, and 7 can begin, safety data will be reviewed by an SRC. Safety data from Cohorts 2, 3 and 4 will be blinded for the principal investigators and the medical monitor in the SRC. Safety data will be unblinded for the three independent members of the SRC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
39
CPV-104 or Placebo
CPV-104
Medizinische Universität Wien
Vienna, Austria
RECRUITINGCliniques universitaires Saint-Luc
Brussels, Belgium
NOT_YET_RECRUITINGFakultni Thomayerova nemocnice
Prague, Czechia
RECRUITINGHôpital Européen Georges-Pompidou HEGP
Paris, France
NOT_YET_RECRUITINGCentre Hospitalier Universitaire De Toulouse
Toulouse, France
NOT_YET_RECRUITINGLaiko General Hospital Of Athens
Athens, Greece
NOT_YET_RECRUITINGPauls Stradins Clinical University Hospital
Riga, Latvia
RECRUITINGVilnius University Hospital Santaros Klinikos
Vilnius, Lithuania
RECRUITINGAmsterdam UMC Stichting
Amsterdam, Netherlands
RECRUITINGHospital Curry Cabral - Centro Hospitalar de Lisboa Central - ULS Sao José
Lisbon, Portugal
RECRUITING...and 6 more locations
Incidence of severe drug reactions (severe ADRs) and serious adverse drug reactions (SADRs)
Time frame: Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse drug reactions (ADRs)
Time frame: Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G
Change from baseline in patient reported parameters (patients with C3G only)
Change in scores from baseline from the following patient reported outcome instruments: * EuroQol 5 Dimension 5 Level (EQ 5D 5L) * PROMIS® 29+2 Profile * Kidney Disease Quality of Life - Short Form (KDQOL SF) * Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT Fatigue)
Time frame: Up to Day 50
Change from baseline in physician global assessment (patients with C3G only)
Change from baseline in physician assessed global disease severity using a 0-100 scale (0 = no signs of disease, 100 = worst imaginable severity).
Time frame: Up to Day 50
Change from baseline in safety laboratory parameters, physical examinations, vital signs, and 12-lead ECG parameters
Change from baseline in predefined safety assessments including: * Clinical laboratory tests (chemistry, hematology, coagulation, urinalysis) * Physical examination findings (abnormal findings) * Vital signs (blood pressure, pulse, temperature, respiratory rate) * ECG parameters (PR/PQ, QRS, QT/QTc, heart rate)
Time frame: Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G
Cmax of CPV-104 after single dose (SAD-HV)
Maximum observed plasma concentration of CPV-104 after administration of a single IV dose.
Time frame: Up to Day 29
Tmax of CPV-104 after single dose (SAD-HV)
Time to reach maximum observed plasma concentration of CPV-104 after a single IV dose.
Time frame: Up to Day 29
AUC0-∞ of CPV-104 after single dose (SAD-HV)
Area under the plasma concentration-time curve from zero to infinity after a single IV dose of CPV-104.
Time frame: Up to Day 29
Terminal half-life (t½) of CPV-104 after single dose (SAD-HV)
Terminal elimination half-life of CPV-104 after a single IV dose.
Time frame: Up to Day 29
Clearance (CL) of CPV-104 after single dose (SAD-HV)
Total body clearance of CPV-104 from plasma after a single IV dose.
Time frame: Up to Day 29
Volume of distribution (Vz) of CPV-104 after single dose (SAD-HV)
Volume of distribution of CPV-104 during the terminal phase after a single IV dose.
Time frame: Up to Day 29
Cmax of CPV-104 after first dose (MAD-C3G)
Maximum observed plasma concentration of CPV-104 after the first weekly dose in the multiple-dose phase.
Time frame: Up to Day 50
Tmax of CPV-104 after first dose (MAD-C3G)
Time to reach maximum observed plasma concentration of CPV-104 after the first weekly dose in the multiple-dose phase.
Time frame: Up to Day 50
AUCτ of CPV-104 after first dose (MAD-C3G)
Area under the plasma concentration-time curve over the dosing interval after the first weekly dose of CPV-104.
Time frame: Up to Day 50
Cmax of CPV-104 after fourth dose (MAD-C3G)
Maximum observed plasma concentration of CPV-104 after the fourth weekly dose in the multiple-dose phase.
Time frame: Up to Day 50
Tmax of CPV-104 after fourth dose (MAD-C3G)
Time to reach maximum observed plasma concentration of CPV-104 after the fourth weekly dose in the multiple-dose phase.
Time frame: Up to Day 50
AUCτ of CPV-104 after fourth dose (MAD-C3G)
Area under the plasma concentration-time curve over the dosing interval after the fourth weekly dose of CPV-104.
Time frame: Up to Day 50
AUC0-∞ of CPV-104 after fourth dose (MAD-C3G)
Area under the plasma concentration-time curve extrapolated to infinity after the fourth weekly dose of CPV-104.
Time frame: Up to Day 50
Terminal half-life (t½) of CPV-104 after fourth dose (MAD-C3G)
Terminal elimination half-life of CPV-104 after the fourth weekly dose.
Time frame: Up to Day 50
Clearance (CL) of CPV-104 after fourth dose (MAD-C3G)
Total body clearance of CPV-104 from plasma after the fourth weekly dose.
Time frame: Up to Day 50
Volume of distribution (Vz) of CPV-104 after fourth dose (MAD-C3G)
Volume of distribution of CPV-104 during the terminal phase after the fourth weekly dose.
Time frame: Up to Day 50
Cmax of endogenous Factor H after single dose (SAD-HV)
Maximum observed plasma concentration of endogenous Factor H measured at the same pharmacokinetic timepoints as CPV-104 following a single IV dose.
Time frame: Up to Day 29
Tmax of endogenous Factor H after single dose (SAD)
Time to reach maximum observed plasma concentration of endogenous Factor H following a single IV dose.
Time frame: Up to Day 29
AUC0-∞ of endogenous Factor H after single dose (SAD)
Area under the plasma concentration-time curve from zero to infinity for endogenous Factor H following a single IV dose.
Time frame: Up to Day 29
Cmax of endogenous Factor H after first dose (MAD-C3G)
Maximum observed plasma concentration of endogenous Factor H measured at the same pharmacokinetic timepoints as CPV-104 after the first weekly dose in the multiple-dose phase.
Time frame: Up to Day 8
Tmax of endogenous Factor H after first dose (MAD-C3G)
Time to reach maximum observed plasma concentration of endogenous Factor H after the first weekly dose in the multiple-dose phase.
Time frame: Up to Day 8
AUCτ of endogenous Factor H after first dose (MAD-C3G)
Area under the plasma concentration-time curve over the dosing interval for endogenous Factor H after the first weekly dose.
Time frame: Up to Day 8
Cmax of endogenous Factor H after fourth dose (MAD-C3G)
Maximum observed plasma concentration of endogenous Factor H after the fourth weekly dose in the multiple-dose phase.
Time frame: Up to Day 50
Tmax of endogenous Factor H after fourth dose (MAD-C3G)
Time to reach maximum observed plasma concentration of endogenous Factor H after the fourth weekly dose.
Time frame: Up to Day 50
AUCτ of endogenous Factor H after fourth dose (MAD-C3G)
Area under the plasma concentration-time curve over the dosing interval for endogenous Factor H after the fourth weekly dose.
Time frame: Up to Day 50
AUC0-∞ of endogenous Factor H after fourth dose (MAD-C3G)
Area under the plasma concentration-time curve from zero to infinity for endogenous Factor H after the fourth weekly dose.
Time frame: Up to Day 50
Incidence and titers of anti-drug antibodies (ADA)
Time frame: Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G
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