Safety and Efficacy Study of OMS906 in Patients With C3G and ICGN

Официальное название

A Phase 2 Proof of Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of OMS906 in Patients With C3 Glomerulopathy (C3G) and Idiopathic Immune Complex-Mediated Glomerulonephritis (ICGN)

Обзор

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of OMS906 in patients with C3 Glomerulopathy (C3G) and Idiopathic Immune Complex-Mediated Glomerulonephritis (ICGN)

Подробное описание

This is a multicenter, open-label, uncontrolled, non-comparative, fixed-dose study. The primary objective is to assess safety and tolerability of OMS906 in patients with C3G or idiopathic ICGN, both complement-mediated disorders. Patients will receive 5 mg/kg administered as intravenous (IV) infusions at 4-week intervals. The study will enroll up to approximately 20 patients with C3G or ICGN. Safety will be evaluated in all patients and by disease cohort. Preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) will be evaluated by disease cohort.

Вмешательства

• Препарат OMS906 study drug
  OMS906 study drug dose 5mg/kg IV administration at 4-week internals

Первичные конечные точки

• To assess OMS906 5mg/kg IV administration at 4-week intervals in patients with C3G and ICGN. [Срок оценки: 48 weeks]

Вторичные конечные точки (10)

• Change in proteinuria measured by 24-hour urine protein/creatinine ratio (UPCR). [Срок оценки: 12, 24, 48 weeks]
• Change in proteinuria measured by 24-hour urine protein excretion (UPE). [Срок оценки: 12, 24, and 48 weeks.]
• Change in proteinuria measured as 24-hour urine albumin excretion (UAE). [Срок оценки: Time Frame: 12, 24, and 48 weeks.]
• Change in proteinuria measured as 24-hour urine albumin/creatinine ratio (UACR). [Срок оценки: 12, 24, and 48 weeks.]
• Incidence of participants with a change from baseline of estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at 24 and 48 weeks. [Срок оценки: 24 and 48 weeks]
• Incidence of participants with a change from baseline serum creatinine concentration at 24 and 48 weeks. [Срок оценки: 24 and 48 weeks]
• Pharmacodynamics (PD) of multiple-dose administration of OMS906. [Срок оценки: 48 weeks]
• Pharmacokinetics (PK) of multiple-dose administration of OMS906 - Cmax. [Срок оценки: 48 weeks]
• Pharmacokinetics (PK) of multiple-dose administration of OMS906 - AUC. [Срок оценки: 48 weeks]
• OMS906 anti-drug antibodies (ADA). [Срок оценки: 48 weeks]

Критерии участия

Критерии включения

• Male or female adults 18 years and older.
• Competent to provide informed consent and has completed informed consent procedures.
• Diagnosis of C3G, including dense deposit disease, or ICGN confirmed by biopsy within 36 months of screening.
• Two 24-hour UPCR ≥ 0.8 gm/gm with the 2 collections separated by 14 - 28 days.
• GFR estimated by the CKD-EPI equation ≥ 45 mL/min/1.73 m2.
• Serum C3 concentration less than the lower limit of laboratory normal during screening.
• Must be on stable maximally tolerated or allowed dose of ACE inhibitor or ARB for at least 90 days.
• If receiving a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, must be on a stable dose for at least 90 days.
• If receiving mycophenolate mofetil, a mineralocorticoid receptor antagonist, or a corticosteroid, must be on stable dose for at least 90 days.
• Have current vaccination status for Neisseria meningitidis, Streptococcus pneumonia and Haemophilus influenza (where available) and agree to maintain vaccination throughout the study.

Patients who have not received these vaccinations at the time of screening may be vaccinated at any time prior to 2 weeks before the first study drug administration. Vaccine serotypes will be chosen by the local standard of care and serotype prevalence.

• Female patients of child-bearing potential must have a negative highly sensitive pregnancy test at screening and prior to each dose of OMS906.
• Females must use highly effective birth control\* to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug.
• Males must use highly effective birth control\* with a female partner to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug.

Критерии исключения

• History of major organ transplant or hematopoietic stem cell/marrow transplant.
• Have known congenital deficiency of any of complement factors C1q, C1r, C1s, C2 or C4.
• Have rapidly progressing glomerulonephritis defined as a 50% or greater decline in the eGFR within 3 months with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli.
• Have renal biopsy findings showing interstitial fibrosis/tubular atrophy of more than 50%.
• Immunodeficiency or treatment with immunosuppressive agents (except mycophenolate mofetil or corticosteroids at the prednisone equivalent of ≤ 7.5 mg/day in patients with C3G only) within 90 days of screening.
• Treatment with rituximab within 6 months of screening.
• Resting blood pressure > 140/90 mmHg during screening.
• History of any active malignancy within 5 years of screening except non-melanoma skin cancers.
• History of monoclonal gammopathy of unknown significance or any autoimmune disorder.
• Elevation of liver function tests, defined as total bilirubin > 2 × upper limit of normal (ULN), direct bilirubin > 1.5 × ULN, and elevated transaminases, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × ULN.
• History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation.
• Significant active bacterial or viral infection within the 2 weeks prior to screening including Covid-19 infection.
• Use of any other complement inhibitor within 6 months prior to the screening visit.
• Have human immunodeficiency virus, hepatitis B, or untreated hepatitis C infection.
• Pregnant, planning to become pregnant, or nursing female patient.
• Recent surgery requiring general anesthesia within the 2 weeks prior to screening or expected to have surgery requiring general anesthesia during the treatment period.
• History of any significant medical, neurologic, or psychiatric disorder that in the opinion of the investigator would make the patient unsuitable for participation in the study.
• Treatment with any investigational medicinal product or investigational device within 30 days (or within 5 × its half-life in days, whichever is the longer period) prior to screening, or participation in another concurrent clinical trial involving a therapeutic intervention. Participation in observational and/or registry studies is permitted.
• Unable or unwilling to comply with the requirements of the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Литва · 2 центра

• Omeros Investigational Site — Kaunas
• Omeros Investigational Site — Vilnius

Великобритания · 2 центра

• Omeros Investigational Site — Leicester
• Omeros Investigational Site — Newcastle upon Tyne

Новая Зеландия · 1 центр

• Omeros Investigational Site — Auckland

Польша · 1 центр

• Omeros Investigational Site — Lodz

Идентификаторы

NCT: NCT06209736 · OMS906-C3G-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗