Can a gene-silencing drug calm overactive complement in kidney disease?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Body weight ≥ 40 kg, Body Mass Index (BMI) \< 32.5 kg/m² * Within the five years prior to screening, patients must have been diagnosed with primary IgAN or PMN through renal biopsy, or within one year prior to screening, diagnosed with C3G or IC-MPGN through renal biopsy, accompanied by glomerular C3 deposition; if a renal biopsy has not been previously performed, a renal biopsy must be conducted during the screening period to confirm eligibility criteria. * Participants with IgAN and C3G/IC-MPGN: During the screening period, morning urine UPCR or 24-hour UPCR ≥0.75 g/g or 24-hour UP ≥1 g/day, with the average of two 24-hour UPCR measurements at baseline ≥0.75 g/g; PMN participants: During the screening period, morning urine or 24-hour UP ≥3.5 g/day, with the average of two 24-hour UP measurements at baseline ≥3.5 g/day. * During the screening and baseline periods, eGFR ≥ 30 ml·min-¹·1.73 m-² (using the CKD-EPI formula) * Prior to the first administration, the patient should have received the maximum tolerated dose or the maximum dose recommended in the instructions of an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) for at least 12 weeks, and the dose of the ACEi or ARB should have been stable for at least 4 weeks before the first administration. * Voluntarily receive meningococcal and pneumococcal vaccines at least 2 weeks before the first administration of the investigational drug in accordance with the protocol requirements. * From the time of signing the informed consent form until 12 months after the last administration of the investigational drug, there are no plans for sperm or egg donation, no plans for pregnancy, and voluntary use of effective contraceptive measures. Exclusion Criteria: * Renal biopsy pathology indicates tubular atrophy or interstitial fibrosis exceeding 50%. * Renal biopsy pathology indicates crescent formation in more than 50% of glomeruli, or clinical presentation suggests the possibility of rapidly progressive glomerulonephritis (RPGN) (eGFR decline ≥50% within 3 months). * Participants were evaluated by the investigator as having IgAN, C3G, IC-MPGN, or PMN secondary to conditions such as infection, autoimmune diseases, or monoclonal immunoglobulin-associated diseases. * Participants were evaluated by the investigator as having other systemic diseases or other kidney diseases that could lead to proteinuria, such as diabetic nephropathy, IgA vasculitis, lupus nephritis, or ANCA-associated small vessel vasculitis. * Participants were determined to have acute kidney injury (AKI) within 30 days prior to screening and before administration of the study drug. * Participants were on dialysis at the time of screening or might require dialysis treatment during the study. * Participants had received B cell-targeting biologics, such as rituximab or ocrelizumab, within 180 days prior to the first administration of the study drug. * Participants had used other biologics, such as infliximab or eculizumab, within 90 days prior to the first administration of the study drug. * Participants who received sodium-glucose co-transporter 2 inhibitors (SGLT2i) within 90 days prior to the first administration of the study drug are excluded, except for those who had been on stable SGLT2i therapy for 90 days or more prior to the first administration and continued stable use during the study. * Participants who received mineralocorticoid receptor antagonists (MRA), such as spironolactone, eplerenone, or finerenone, within 30 days prior to the first administration of the study drug are excluded, except for those who had been on stable MRA therapy for 90 days or more prior to the first administration and continued stable use during the study. * Participants with a history of kidney transplantation, organ transplantation, or hematopoietic stem cell transplantation are excluded. * Participants with any history of malignancy within 5 years prior to screening are excluded, except for those who have been cured (such as basal cell carcinoma, cutaneous squamous cell carcinoma, low-risk/very low-risk localized prostate cancer, papillary thyroid carcinoma, etc.) or have undergone radical resection of carcinoma in situ (such as ductal carcinoma in situ of the breast, cervical carcinoma in situ, etc.). * History of active tuberculosis within 1 year prior to screening, or deemed by the investigator to have active tuberculosis at screening. * Participants with chronic recurrent infections within 1 year prior to screening, such as liver abscess, chronic pyelonephritis, etc. * Surgery requiring general anesthesia or hospitalization for more than 1 day within 30 days prior to screening or planned during the trial. * Administration of live attenuated vaccines other than those allowed in the protocol within 30 days prior to screening or planned during the study. * Clinically significant infection requiring systemic anti-infective treatment within 30 days prior to the first administration of the investigational product. * History of recurrent invasive infections with encapsulated bacteria (e.g., Neisseria meningitidis and Streptococcus pneumoniae). * History of severe drug allergy, or allergic reaction to oligonucleotides or N-acetylgalactosamine (GalNAc). * Poorly controlled type 1 or type 2 diabetes, defined as baseline glycated hemoglobin (HbA1c) ≥7.0%. * Poorly controlled hypertension, defined as baseline seated resting systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. * History of renal artery stenosis, chronic hyperkalemia, or other contraindications to RAS inhibitors (RASi).