C3 Glomerulopathy (C3G), Healthy Adult Participants
Conditions
Keywords
CPV-104, C3G, Complement System, kidney disease, kidney, Factor H
Brief summary
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.
Detailed description
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.
Interventions
DRUGCPV-104/Placebo
CPV-104 or Placebo
DRUGCPV-104
CPV-104
Sponsors
eleva GmbH
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Part 1 - SAD-HV: Single ascending dose in healthy volunteers, Part 2 - MAD-C3G: Multiple ascending dose in C3G patients
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Healthy Volunteers (Part 1 - SAD-HV) : * Participants must be at least 18 years old and no more than 50 years old, at the time of consent, and must be able to sign and date the informed consent form (ICF) themselves. * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the
Exclusion criteria
that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or results. * Body weight within 50 kg for male/ 45 kg for female to 110 kg and BMI within the range 18 - 32 kg/m2 (inclusive). * Childbearing potential (CBP) participants should agree to use a highly effective method of contraception throughout the study and for 90 days after the last dose of the IMP. * CBP participants should agree not to donate oocytes or freeze for future use for the purposes of assisted reproduction during the study and for a period of 90 days after the last dose of the IMP. Male participants should agree not to donate sperm or freeze sperm for future use for the purposes of assisted reproduction during the study and for a period of 90 days after the last dose of the IMP. * CBP participants should have a negative pregnancy test at screening. * Participant provides written informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of severe drug reactions (severe ADRs) and serious adverse drug reactions (SADRs) | Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) | 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) | Up to Day 50 | 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) |
| Change from baseline in physician global assessment (patients with C3G only) | Up to Day 50 | Change from baseline in physician assessed global disease severity using a 0-100 scale (0 = no signs of disease, 100 = worst imaginable severity). |
| Change from baseline in safety laboratory parameters, physical examinations, vital signs, and 12-lead ECG parameters | Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G | 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) |
| Cmax of CPV-104 after single dose (SAD-HV) | Up to Day 29 | Maximum observed plasma concentration of CPV-104 after administration of a single IV dose. |
| Tmax of CPV-104 after single dose (SAD-HV) | Up to Day 29 | Time to reach maximum observed plasma concentration of CPV-104 after a single IV dose. |
| AUC0-∞ of CPV-104 after single dose (SAD-HV) | Up to Day 29 | Area under the plasma concentration-time curve from zero to infinity after a single IV dose of CPV-104. |
| Terminal half-life (t½) of CPV-104 after single dose (SAD-HV) | Up to Day 29 | Terminal elimination half-life of CPV-104 after a single IV dose. |
| Clearance (CL) of CPV-104 after single dose (SAD-HV) | Up to Day 29 | Total body clearance of CPV-104 from plasma after a single IV dose. |
| Volume of distribution (Vz) of CPV-104 after single dose (SAD-HV) | Up to Day 29 | Volume of distribution of CPV-104 during the terminal phase after a single IV dose. |
| Cmax of CPV-104 after first dose (MAD-C3G) | Up to Day 50 | Maximum observed plasma concentration of CPV-104 after the first weekly dose in the multiple-dose phase. |
| Tmax of CPV-104 after first dose (MAD-C3G) | Up to Day 50 | Time to reach maximum observed plasma concentration of CPV-104 after the first weekly dose in the multiple-dose phase. |
| AUCτ of CPV-104 after first dose (MAD-C3G) | Up to Day 50 | Area under the plasma concentration-time curve over the dosing interval after the first weekly dose of CPV-104. |
| Cmax of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Maximum observed plasma concentration of CPV-104 after the fourth weekly dose in the multiple-dose phase. |
| Tmax of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Time to reach maximum observed plasma concentration of CPV-104 after the fourth weekly dose in the multiple-dose phase. |
| AUCτ of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Area under the plasma concentration-time curve over the dosing interval after the fourth weekly dose of CPV-104. |
| AUC0-∞ of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Area under the plasma concentration-time curve extrapolated to infinity after the fourth weekly dose of CPV-104. |
| Terminal half-life (t½) of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Terminal elimination half-life of CPV-104 after the fourth weekly dose. |
| Clearance (CL) of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Total body clearance of CPV-104 from plasma after the fourth weekly dose. |
| Volume of distribution (Vz) of CPV-104 after fourth dose (MAD-C3G) | Up to Day 50 | Volume of distribution of CPV-104 during the terminal phase after the fourth weekly dose. |
| Cmax of endogenous Factor H after single dose (SAD-HV) | Up to Day 29 | Maximum observed plasma concentration of endogenous Factor H measured at the same pharmacokinetic timepoints as CPV-104 following a single IV dose. |
| Tmax of endogenous Factor H after single dose (SAD) | Up to Day 29 | Time to reach maximum observed plasma concentration of endogenous Factor H following a single IV dose. |
| AUC0-∞ of endogenous Factor H after single dose (SAD) | Up to Day 29 | Area under the plasma concentration-time curve from zero to infinity for endogenous Factor H following a single IV dose. |
| Cmax of endogenous Factor H after first dose (MAD-C3G) | Up to Day 8 | 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. |
| Tmax of endogenous Factor H after first dose (MAD-C3G) | Up to Day 8 | Time to reach maximum observed plasma concentration of endogenous Factor H after the first weekly dose in the multiple-dose phase. |
| AUCτ of endogenous Factor H after first dose (MAD-C3G) | Up to Day 8 | Area under the plasma concentration-time curve over the dosing interval for endogenous Factor H after the first weekly dose. |
| Cmax of endogenous Factor H after fourth dose (MAD-C3G) | Up to Day 50 | Maximum observed plasma concentration of endogenous Factor H after the fourth weekly dose in the multiple-dose phase. |
| Tmax of endogenous Factor H after fourth dose (MAD-C3G) | Up to Day 50 | Time to reach maximum observed plasma concentration of endogenous Factor H after the fourth weekly dose. |
| AUCτ of endogenous Factor H after fourth dose (MAD-C3G) | Up to Day 50 | Area under the plasma concentration-time curve over the dosing interval for endogenous Factor H after the fourth weekly dose. |
| AUC0-∞ of endogenous Factor H after fourth dose (MAD-C3G) | Up to Day 50 | Area under the plasma concentration-time curve from zero to infinity for endogenous Factor H after the fourth weekly dose. |
| Incidence and titers of anti-drug antibodies (ADA) | Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G | — |
Countries
Austria, Belgium, Czechia, France, Greece, Latvia, Lithuania, Netherlands, Portugal, Serbia, Spain, Sweden
Contacts
CONTACTJulia Flugel
CONTACTDaniela Wittmann
PRINCIPAL_INVESTIGATORBernd Jilma, Prof.
Medical University of Vienna
Outcome results
None listed