Evaluate the Efficacy and Safety of NTQ5082 Capsules in Patients With Primary IgA Nephropathy

Official title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of NTQ5082 Capsules in the Treatment of Patients With Primary IgA Nephropathy

Overview

NTQ5082 is a small molecule inhibitor of complement factor B (CFB) that inhibits the enzymatic activity of CFB, thereby blocking the alternative pathway of the complement activation cascade. It is being clinically developed for the treatment of primary IgA nephropathy The main objectives of the study were to assess the efficacy and safety of NTQ5082 capsules in the treatment of patients with primary IgA nephropathy.

Interventions

• Drug NTQ5082 capsules 100 mg
  NTQ5082 capsules 100 mg
• Drug NTQ5082 capsules 200 mg
  NTQ5082 capsules 200 mg
• Drug NTQ5082 capsules 300 mg
  NTQ5082 capsules 300 mg
• Drug Placebo
  Placebo

Primary outcome measures

• The log-transformed ratio of 24-hour urine protein-to-creatinine ratio (24h-UPCR) compared to baseline after 12 weeks of treatment. [Time frame: Week 12]

Secondary outcome measures (6)

• The log-transformed ratio of 24-hour urine protein-to-creatinine ratio (24h-UPCR) compared to baseline during treatment period except week 12 [Time frame: From week 1 to week 24]
• The change in estimated glomerular filtration rate(eGFR) compared to baseline during treatment period. [Time frame: From week 1 to week 24]
• The change in serum creatinine (SCr) compared to baseline during treatment period. [Time frame: From week 1 to week 24]
• The log-transformed ratios of first morning void (FMV) UPCR and UACR compared to baseline during treatment period [Time frame: From week 1 to week 24]
• The change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale score compared to baseline during the treatment period. [Time frame: From week 1 to week 24]
• Incidence and severity of adverse events [safety and tolerability] [Time frame: 28weeks]

Eligibility criteria

Inclusion criteria

• Age ≥18 years, male or female.
• Body weight ≥40 kg, BMI between 15 to 38 kg/m².
• Diagnosis of primary IgA nephropathy confirmed by renal biopsy within 8 years before screening or during screening.
• 24-hour urine protein excretion (24h-UPE) ≥0.75 g/24h, or first morning void (FMV) urine protein-to-creatinine ratio (UPCR) ≥0.8 g/g.
• Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m².
• Previously vaccinated with ACYW135 meningococcal polysaccharide vaccine and pneumococcal vaccine.
• Received renin-angiotensin system (RAS) inhibitor therapy for at least 12 weeks prior to randomization, with stable treatment at the maximum recommended dose or maximum tolerated dose of RAS inhibitors for at least 4 weeks prior to randomization.
• Agreement to use at least one effective contraceptive method with partners during sexual activity from signing the informed consent form until 4 weeks after the last administration of the investigational product, and refrain from sperm/egg donation during this period.

Exclusion criteria

• Receipt of aldosterone receptor antagonists, renin inhibitors, or medications significantly affecting creatinine levels within 4 weeks or 5 half-lives (whichever is longer) before first investigational product administration.
• Continuous use of systemic corticosteroids, immunosuppressants/modulators, or Chinese herbal medicines with immunosuppressive effects within 12 weeks or 5 half-lives (whichever is longer) before first investigational product administration.
• Treatment with biological agents or complement pathway inhibitors (other than the study drug) within 12 weeks or 5 half-lives (whichever is longer) before first investigational product administration.
• History of gastrointestinal surgery potentially altering drug absorption/distribution/metabolism/excretion, severe gastrointestinal disorders, or conditions causing dysphagia/recurrent vomiting that may interfere with oral medication intake.
• Major trauma/surgery within 12 weeks before screening or planned major surgery during the study.
• Previous bone marrow/hematopoietic stem cell transplantation or solid organ transplantation (e.g., heart, lung, kidney, liver).
• Known/suspected hereditary complement deficiency, or diagnosed primary/severe secondary immunodeficiency.
• Poorly controlled blood pressure as assessed by the investigator.
• Poorly controlled blood glucose as assessed by the investigator.
• Presence of nephrotic syndrome, rapidly progressive glomerulonephritis, renal pathology showing >50% glomerular crescents, or >50% tubular atrophy-interstitial fibrosis.
• Participation in other interventional clinical trials with pharmacological/device interventions within 4 weeks before screening.
• Pregnant/lactating women or those planning pregnancy during the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06982040 · NTQ5082-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗