CPV-104 safety and drug processing in healthy adults and people with C3 glomerulopathy

A Phase 1 First-in-Human Clinical Trial in Healthy Participants and Patients With C3-Glomerulopathy to Assess Safety, Tolerability, and Pharmacokinetics of CPV-104

This trial tests whether CPV-104 is safe, how the body processes it, and whether the immune system reacts to it in healthy adults and adults with C3 glomerulopathy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: eleva GmbH (Industry-sponsored)
• Locations: 16 sites (Vienna and 15 other locations)
• Trial ID: NCT07483827 on ClinicalTrials.gov

What this trial studies

This first-in-human, phase 1 trial has two parts: a randomized, double-blind, placebo-controlled single-ascending-dose (SAD) phase in healthy volunteers and an open-label multiple-ascending-dose (MAD) phase in adults with C3 glomerulopathy (C3G). Healthy volunteers receive a single IV dose of CPV-104 or placebo in successive cohorts, while patients with C3G receive four weekly IV doses without placebo. The trial focuses on safety, tolerability, pharmacokinetics, and immunogenicity, with close monitoring including blood and urine tests, ECGs, vitals, and antibody testing; kidney function is also followed in C3G patients. A Safety Review Committee reviews blinded and unblinded safety data between cohorts to guide dose escalation and participant safety.

Who should consider this trial

Good fit: Ideal candidates are adults with a confirmed diagnosis of C3 glomerulopathy who meet the study's safety criteria, and healthy adults aged 18–50 who meet the required weight, BMI, and screening laboratory criteria.

Not a fit: Patients with advanced or unstable kidney failure, children, pregnant people, or those who do not meet the trial's inclusion/exclusion criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, CPV-104 could offer a new way to control complement overactivity and potentially stabilize or slow kidney damage in people with C3 glomerulopathy.

How similar studies have performed: Other complement-targeting therapies have shown promise in related complement-mediated kidney diseases, but treatment of C3G remains experimental and results have been mixed so far.

Eligibility criteria

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.

Exclusion Criteria Healthy Volunteers (Part 1 - SAD-HV) :

* Participant has a history of clinically significant disorders or diseases affecting the endocrine, gastrointestinal, cardiovascular, hematological, liver, immune, kidney, respiratory, reproductive, or neurological systems (such as stroke or epilepsy). Participants with a history of minor medical issues may be considered for the study at the investigator's discretion.
* Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study.
* Participant has a recent history of febrile illness or other evidence of a clinically significant active infection, within 14 days prior to screening.
* Participant has a history of severe allergies (e.g. to medications, food, or latex) or has experienced an anaphylactic reaction to food or medicine.
* Participant has a known hypersensitivity to any components of the IMP as stated in this protocol.
* Alanine transaminase (ALT) or Aspartate aminotransferase (AST) \>1.5 x upper limit of normal (ULN).
* Total Bilirubin \>1 x ULN, \> 1.5 x ULN if Gilbert's syndrome.
* Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
* Participant has received any complement modifying treatment within 6 months prior to the first dosing day.
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Participation in any other clinical study with a medical device or investigational medicinal product concurrently or within 5 half-life times or 3 months before the first dosing day (whichever is longer).
* Presence of a QTc interval \>450 ms for males or \>460 ms for females, a history of risk factors for Torsades de Pointes (such as heart failure, cardiomyopathy, or a family history of long QT syndrome), uncorrected hypokalemia or hypomagnesemia, or concurrent use of medications known to prolong the QT/QTc interval.
* Participant is an employee of the sponsor or an employee or relative of the investigator.
* Participant is unable to comply with the protocol (e.g. clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the investigator, otherwise unsuited for the study.
* Participant has made a blood donation or blood products within 90 days prior to Baseline or plans to donate blood during the study.
* Participant has an alcohol consumption of more than 21 units (males) or 14 units (females) of alcohol per week. One unit is equivalent to 8 g of alcohol: a half pint (240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits).
* Study participant has a high consumption of caffeine- or other xanthine-containing products (≥300 mg of caffeine- or xanthine-equivalent per day) (1 cup of coffee ≈ 100 mg of caffeine; 1 cup of tea ≈ 30 mg of caffeine; 1 glass of cola ≈ 20 mg of caffeine).

Inclusion Criteria C3G Patient (Part 2 - MAD-C3G):

* Patient must be at least 18 years old, at the time of consent, and must be able to sign and date the informed consent form (ICF) themselves.
* Patient must have a diagnosis of C3G confirmed by historical renal biopsy.
* Patient must have proteinuria at screening.
* Patient must have stable or worsening renal disease, be on stable and optimized symptomatic treatment, in the opinion of the PI, for at least 30 days prior to screening (treatments may include, but are not limited to, immunosuppressive agents, anti-hypertensives, steroids).
* 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.

Exclusion Criteria C3G Patients (Part 2 - MAD-C3G) :

* Patient has a history of clinically significant disorders or diseases affecting the endocrine, gastrointestinal, cardiovascular (including thromboembolic events like deep vein thrombosis, pulmonary embolism, known coagulopathy), hematological, liver, immune, kidney, respiratory, reproductive, or neurological systems (such as stroke or epilepsy). Participants with a history of minor medical issues may be considered for the study at the investigator's discretion.
* Patient has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study.
* Patient had a recent history of febrile illness or other evidence of a clinically significant active infection, within 14 days prior to screening.
* Patient has a history of severe allergies (e.g. to medications, food, or latex) or has experienced an anaphylactic reaction to food or medicine.
* Patient has a known hypersensitivity to any components of the IMP as stated in this protocol.
* Patient had evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G is secondary.
* Patient with other renal diseases that would interfere with interpretation of the study.
* Patient is receiving renal replacement therapy.
* Patient is receiving or planned for receiving plasmapheresis.
* Patient had a major organ transplant (e.g. heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
* Patient had a history or presence of any clinically relevant co-morbidities (e.g. advanced cardiac disease (NYHA class 4), severe pulmonary arterial hypertension (WHO class 4).
* Alanine transaminase (ALT) or Aspartate aminotransferase (AST) \>2 x upper limit of normal (ULN).
* Total Bilirubin \>1 x ULN, \> 1.5 x ULN if Gilbert's syndrome.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
* Patient has received any complement modifying treatment within 6 months prior to the first dosing day.
* Patient in any other clinical study with a medical device or investigational medicinal product concurrently or within 5 half-life times or 3 months before study start (whichever is longer).
* Presence of a QTc interval \>450 ms for males or \>460 ms for females, a history of risk factors for Torsades de Pointes (such as heart failure, cardiomyopathy, or a family history of long QT syndrome), uncorrected hypokalemia or hypomagnesemia, or concurrent use of medications known to prolong the QT/QTc interval.
* Participant is an employee of the sponsor or an employee or relative of the investigator.
* Participant is unable to comply with the protocol (e.g. clinically relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the investigator, otherwise unsuited for the study.
* Participant has made a blood donation or blood products within 90 days prior to Baseline or plans to donate blood during the study.
* Participant has an alcohol consumption of more than 21 units (males) or 14 units (females) of alcohol per week. One unit is equivalent to 8 g of alcohol: a half pint (\~240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits).
* Study participant has a high consumption of caffeine- or other xanthine-containing products (≥300 mg of caffeine- or xanthine-equivalent per day) (1 cup of coffee ≈ 100 mg of caffeine; 1 cup of tea ≈ 30 mg of caffeine; 1 glass of cola ≈ 20 mg of caffeine).

Where this trial is running

Vienna and 15 other locations

• Medizinische Universität Wien — Vienna, Austria (Recruiting)
• Cliniques universitaires Saint-Luc — Brussels, Belgium (Recruiting)
• Fakultni Thomayerova nemocnice — Prague, Czechia (Recruiting)
• Hôpital Européen Georges-Pompidou HEGP — Paris, France (Not_yet_recruiting)
• Centre Hospitalier Universitaire De Toulouse — Toulouse, France (Recruiting)
• Laiko General Hospital Of Athens — Athens, Greece (Recruiting)
• Pauls Stradins Clinical University Hospital — Riga, Latvia (Recruiting)
• Vilnius University Hospital Santaros Klinikos — Vilnius, Lithuania (Recruiting)
• Amsterdam UMC Stichting — Amsterdam, Netherlands (Recruiting)
• Hospital Curry Cabral - Centro Hospitalar de Lisboa Central - ULS Sao José — Lisbon, Portugal (Recruiting)
• Fundacio Puigvert — Barcelona, Spain (Not_yet_recruiting)
• Hospital Universitario 12 De Octubre — Madrid, Spain (Recruiting)
• Clinica Universidad De Navarra — Pamplona, Spain (Recruiting)
• Hospital Universitario Virgen De La Macarena — Seville, Spain (Recruiting)
• University Hospital Virgen Del Rocio S.L. — Seville, Spain (Recruiting)
• Karolinska University Hospital — Huddinge, Sweden (Recruiting)

Study contacts

• Principal investigator: Bernd Jilma, Prof. — Medical University of Vienna
• Study coordinator: Julia Flugel

Conditions C3 Glomerulopathy; Healthy Adult Participants; CPV-104; C3G; Complement System; kidney disease; kidney; Factor H