A Clinical Trial to Test the Safety, Tolerability, and How the Body Processes CPV-104 in Healthy People and Patients With C3-Glomerulopathy

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат CPV-104/Placebo
  CPV-104 or Placebo
• Препарат CPV-104
  CPV-104

Первичные конечные точки

• Incidence of severe drug reactions (severe ADRs) and serious adverse drug reactions (SADRs) [Срок оценки: Up to Day 29 for Part 1 - SAD-HV and up to Day 50 for Part 2 - MAD-C3G]

Вторичные конечные точки (12)

• Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) [Срок оценки: 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) [Срок оценки: Up to Day 50]
• Change from baseline in physician global assessment (patients with C3G only) [Срок оценки: Up to Day 50]
• Change from baseline in safety laboratory parameters, physical examinations, vital signs, and 12-lead ECG parameters [Срок оценки: 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) [Срок оценки: Up to Day 29]
• Tmax of CPV-104 after single dose (SAD-HV) [Срок оценки: Up to Day 29]
• AUC0-∞ of CPV-104 after single dose (SAD-HV) [Срок оценки: Up to Day 29]
• Terminal half-life (t½) of CPV-104 after single dose (SAD-HV) [Срок оценки: Up to Day 29]
• Clearance (CL) of CPV-104 after single dose (SAD-HV) [Срок оценки: Up to Day 29]
• Volume of distribution (Vz) of CPV-104 after single dose (SAD-HV) [Срок оценки: Up to Day 29]
• Cmax of CPV-104 after first dose (MAD-C3G) [Срок оценки: Up to Day 50]
• Tmax of CPV-104 after first dose (MAD-C3G) [Срок оценки: Up to Day 50]

Критерии участия

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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Испания · 5 центров

• Fundacio Puigvert — Barcelona
• Hospital Universitario 12 De Octubre — Madrid
• Clinica Universidad De Navarra — Pamplona
• Hospital Universitario Virgen De La Macarena — Seville
• University Hospital Virgen Del Rocio S.L. — Seville

Франция · 2 центра

• Hôpital Européen Georges-Pompidou HEGP — Paris
• Centre Hospitalier Universitaire De Toulouse — Toulouse

Австрия · 1 центр

• Medizinische Universität Wien — Vienna

Бельгия · 1 центр

• Cliniques universitaires Saint-Luc — Brussels

Чехия · 1 центр

• Fakultni Thomayerova nemocnice — Prague

Греция · 1 центр

• Laiko General Hospital Of Athens — Athens

Латвия · 1 центр

• Pauls Stradins Clinical University Hospital — Riga

Литва · 1 центр

• Vilnius University Hospital Santaros Klinikos — Vilnius

Нидерланды · 1 центр

• Amsterdam UMC Stichting — Amsterdam

Португалия · 1 центр

• Hospital Curry Cabral - Centro Hospitalar de Lisboa Central - ULS Sao José — Lisbon

Сербия · 1 центр

• University Clinical Center of Serbia — Belgrade

Швеция · 1 центр

• Karolinska University Hospital — Huddinge

Идентификаторы

NCT: NCT07483827 · CPV-104-101 · 2024-517992-19-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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