Evaluation of OMS906 Safety and Efficacy in Patients with C3 Glomerulopathy and Idiopathic Immune Complex-Mediated Glomerulonephritis
- Trial ID
- 2023-508669-33-00
- Protocol
- OMS906-C3G-001
- Sponsor
- Omeros Corp.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the overall **safety** and **tolerability** of 5 mg/kg repeat-dose OMS906 administered intravenously at 4-week intervals in patients diagnosed with C3 Glomerulopathy (C3G) and Idiopathic Immune Complex-Mediated Glomerulonephritis (ICGN). This is clinically relevant as it aims to ensure that the treatment is safe for patients, which is a critical consideration before assessing its efficacy.
Secondary objectives include:
- Assessing preliminary efficacy by changes from baseline in **proteinuria**, measured as 24-hour urine protein/creatinine ratio (UPCR) and urine protein excretion (UPE) at 12, 24, and 48 weeks.
- Evaluating changes from baseline in **albuminuria**, measured as 24-hour urine albumin/creatinine ratio (UACR) and urine albumin excretion (UAE) at 12, 24, and 48 weeks.
- Assessing changes from baseline in estimated **glomerular filtration rate** (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at 24 and 48 weeks.
- Evaluating changes from baseline in serum **creatinine** concentration at 24 and 48 weeks.
- Assessing pharmacokinetics (PK) and pharmacodynamics (PD) by mature (activated) complement factor D (FD) and anti-drug antibodies.
Participants
The clinical trial involves a total of **10 participants** diagnosed with **C3 Glomerulopathy** (C3G) and **Idiopathic Immune Complex-Mediated Glomerulonephritis** (ICGN). The study population comprises both male and female adults aged 18 years and older. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of C3G or ICGN by biopsy within 36 months of screening, and a serum C3 concentration below the laboratory's normal range during screening. All participants are required to have a stable health status, particularly in terms of their renal function, with a glomerular filtration rate (GFR) estimated by the CKD-EPI equation of at least 30 mL/min/1.73m². Lifestyle considerations include maintaining a stable dose of certain medications such as ACE inhibitors, ARBs, SGLT-2 inhibitors, mycophenolate mofetil, mineralocorticoid receptor antagonists, or corticosteroids for at least 90 days prior to the study. Participants must also have an up-to-date vaccination status for Neisseria meningitidis, Streptococcus pneumonia, and Haemophilus influenza, and agree to maintain this status throughout the study. The trial includes a vulnerable population, and all participants are required to provide informed consent. The study does not specify any particular dietary or physical activity requirements beyond the medication stability and vaccination criteria.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and tolerability of the investigational drug OMS906 in patients diagnosed with C3 Glomerulopathy and Idiopathic Immune Complex-Mediated Glomerulonephritis. This is a Phase II, randomized, double-blind, controlled study. The trial will involve the administration of OMS906 via intravenous infusion at a dose of 5 mg/kg, repeated every four weeks. The maximum treatment period is 48 weeks, with the trial expected to conclude by September 2025.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age, vaccination status, and stable medication use. The screening will also involve a biopsy-confirmed diagnosis of the relevant conditions within 36 months prior to the trial. Following the screening, participants will receive the study drug at regular intervals, with follow-up visits scheduled to monitor safety and efficacy outcomes. These visits will include assessments of adverse events, vital signs, electrocardiograms, and laboratory tests. Secondary endpoints will measure changes in proteinuria and estimated glomerular filtration rate (eGFR) at specified intervals.
The expected duration of participant involvement is up to 48 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The end-of-study visit will occur after the final dose, where comprehensive evaluations will be conducted to assess the overall impact of the treatment. Participants are required to maintain effective birth control measures throughout the study and for 20 weeks following the last dose to prevent pregnancy. The trial aims to provide valuable insights into the pharmacokinetics and pharmacodynamics of OMS906, contributing to the understanding of its potential therapeutic benefits in the target patient population.
Treatment
The clinical trial involves the administration of **OMS906**, an investigational medicinal product developed by OMEROS CORPORATION. **OMS906** is a **solution for injection** and is classified as a biological/biotechnological product of protein origin. The active substance, also named **OMS906**, is administered via **intravenous infusion**. The dosing regimen for this trial is set at 5 mg/kg, with a maximum total dose of 65 mg/kg over the course of the study. The treatment is administered at 4-week intervals, with a maximum treatment period of 48 weeks. The primary objective of the trial is to evaluate the safety and tolerability of this dosing schedule in patients diagnosed with C3 Glomerulopathy (C3G) and Idiopathic Immune Complex-Mediated Glomerulonephritis (ICGN).
In addition to the experimental treatment, the study may include the use of standard-of-care therapies as deemed necessary by the clinical investigators. These therapies are not specified in the trial documentation and will be administered according to the standard medical practice for the conditions being studied. No placebo or active comparator treatment is mentioned in the trial protocol. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen and to assess the overall safety and efficacy of **OMS906**.
Efficacy
The efficacy of OMS906 in the clinical trial will be assessed through a series of secondary endpoints. These endpoints include the change from baseline in proteinuria, which will be measured using 24-hour urine protein-to-creatinine ratio (UPCR), urine protein excretion (UPE), urine albumin-to-creatinine ratio (UACR), and urine albumin excretion (UAE) at 12, 24, and 48 weeks. Additionally, changes from baseline in estimated glomerular filtration rate (eGFR), calculated by the CKD-EPI formula, and serum creatinine levels will be evaluated at 24 and 48 weeks. Pharmacokinetic (PK) parameters of OMS906 will be estimated using appropriate population PK methods based on sparse sampling, and pharmacodynamic (PD) parameters, including mature FD, will be measured as changes from baseline. The incidence of anti-drug antibodies (ADAs) in serum will also be monitored as part of the efficacy assessment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 ≥ 30 mL/min/1.73m2.
- Serum C3 concentration less than the lower limit of laboratory normal during the 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.
Exclusion Criteria
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Lithuania | Not Recruiting | 28 Mar 2024 | 5 |
 Poland | Not Recruiting | 28 Mar 2024 | 5 |