Efficacy and Safety Study of HS-10542 for IgA Nephropathy

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose-Ranging Study to Evaluate the Efficacy and Safety of HS-10542 Capsules in Primary Immunoglobulin A (IgA) Nephropathy

Обзор

This is a multicenter, randomized, double-blind, parallel, placebo-controlled study and is being conducted to evaluate the efficacy and safety of HS-10542 capsules for primary IgA nephropathy.

Подробное описание

This is a Phase 2, randomized, double-blind, parallel, placebo-controlled study in patients aged 18 years or above with biopsy confirmed diagnosis of IgA nephropathy. The clinical trial is designed to test the effectiveness and safety of multiple doses of HS-10542. The main objectives is to evaluate the dose response of different doses of HS-10542 by measuring urine protein-to-creatinine ratio (UPCR).

The trial is comprised of three main periods, Screening, Treatment (24 weeks) and Follow-Up (4 weeks). Approximately 90 patients will be enrolled. The findings from this study will form the basis for subsequent clinical development of HS-10542.

Вмешательства

• Препарат HS-10542 High Dose
  Drug: HS-10542 High Dose, QD
• Препарат HS-10542 Low Dose
  Drug: HS-10542 Low Dose, QD
• Препарат Placebo
  Placebo, QD

Первичные конечные точки

• Ratio to baseline in Urine Protein to Creatinine Ratio (sampled from 24h urine collection) [Срок оценки: Baseline and Week 12]

Вторичные конечные точки (12)

• Incidence and severity of adverse events of HS-10542 at each dosing [Срок оценки: Baseline to End of Study (week 24)]
• Changes from baseline in blood pressures [Срок оценки: Baseline to End of Study (week 24)]
• Changes from baseline in heart rate [Срок оценки: Baseline to End of Study (week 24)]
• Changes from baseline in body temperature [Срок оценки: Baseline to End of Study (week 24)]
• Changes from baseline in electrocardiogram (ECG) intervals [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in white blood cell count [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in hemoglobin [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in platelet count [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in alanine aminotransferase [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in aspartate aminotransferase [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in total bilirubin [Срок оценки: Baseline to End of Study (week 24)]
• Change from baseline in serum creatinine [Срок оценки: Baseline to End of Study (week 24)]

Критерии участия

Критерии включения

• Participant is a male or female≥18 years and≤74 years of age at the time of signing the informed consent.
• Body weight≥35kg, BMI<37.5kg/m2.
• Primary IgA nephropathy was confirmed by renal biopsy within 8 years.
• 24-hour urine protein excretion≥1.0g/24h, or UPCR≥0.8g/g at screening and prior to randomization.
• eGFR≥30 ml/min/1.73m2 at screening and prior to randomization；
• A fertile female participant or a male participant whose partner is a fertile female, who has not had a fertility, sperm/egg donation plan and voluntarily takes highly effective contraceptive measures (including the partner).
• All participants received RAS blocker treatment at least for 12 weeks, or demonstrated intolerance to RAS blockers, but has received SGLT2 inhibitors, endothelin receptor antagonists, or a mineralocorticoid receptor antagonist for at least 12 weeks, and have achieved the maximum recommended dose according to the product label or the maximum tolerated dose with stable dosing for at least 4 weeks prior to randomization.
• Participants should be able to complete vaccinations against Neisseria meningitidis (types A, C, Y, and W-135) and streptococcus pneumoniae at least 2 weeks prior to the first dose.
• Understand the research procedures and methods, voluntarily participate in this trial, and sign the informed consent form in person.

Критерии исключения

• Participants with a history of severe allergies to drugs, food or the environment, or allergic to any RAS blockers, investigational products, or components as evaluated by the investigator;
• Participant has secondary forms of IgAN as defined by investigator (eg, IgA vasculitis nephritis, SLE) or participant has nephrotic syndrome (defined as proteinuria>3.5 g/day and serum albumin<3.0 g/dL, with or without edema);
• IgA nephropathy with rapid decline of renal function; Kidney pathology indicated that more than 50% of the glomerulus had large crescent body formation, which may affect the study results; Tubule atrophy - interstitial fibrosis of more than 50%;
• Patients with concomitant immunodeficiency disorders; or those with other systemic diseases assessed by the investigator as potentially causing proteinuria (e.g., diabetic nephropathy, autoimmune diseases, ANCA-associated vasculitis, etc.);
• Any organ transplant recipient, including those who have undergone solid organ transplants, bone marrow transplants and haematopoietic stem cell transplants.
• Participants with a medical history of invasive infections caused by capsulated bacteria, including Neisseria meningitidis and Streptococcus pneumoniae;
• Participants with chronic recurrent infections within 1 year prior to screening, such as liver abscess and pyelonephritis; Or participants with active infection who requiring intravenous antibiotic therapy within 2 weeks prior to randomization;
• Participants have a history of malignancy (except of radical excision of basal cell or squamous cell skin cancer, or cervical carcinoma in situ.), Participants with prior malignancy who have been documented to be cancer-free for≥5 years may be enrolled;
• Participants with a history of severe trauma or major surgery within 12 weeks prior to screening, or who plan to undergo surgery during the study period;
• Participants with a history of blood donation or a history of severe blood loss (≥400 mL blood loss) within 12 weeks prior to screening, or who have received blood transfusions within 12 weeks prior to screening;
• Participants had received systemic glucocorticoid therapy, immunosuppressive agents (e.g. mycophenolate mofetil or calcineurin inhibitors), Chinese patent medicines with immunosuppressive properties (e.g. Tripterygium wilfordii tablets), or renin inhibitors within 12 weeks of randomisation. Alternatively, they were assessed by the investigator as potentially requiring such treatments during the study period.
• Participants had received treatment with biologics (e.g. telitacicept, atacicept, povetacicept, sibeprenlimab, CD38 monoclonal antibodies), or with budesonide enteric capsules (NEFECON) or cytokine inhibitors, as well as other products related to the complement pathway (e.g. eculizumab, ravulizumab and avacopan), which were not included in the investigational drug of this study within 6 months prior to randomisation, or participants had received iptacopan within 12 weeks prior to randomization;
• Participants have a history of gastrointestinal surgery that may significantly affect the absorption, distribution, metabolism or excretion of drugs. Or have a history of severe gastrointestinal disease, or be experiencing symptoms of dysphagia or recurrent vomiting that cause difficulty eating or taking medication.
• Participants with poorly controlled severe systemic diseases at screening, including, but not limited to, severe hypertension (SBP≥180 mmHg and/or DBP110 mmHg), severe cardiac disease, pulmonary disease, hepatic disease or haematological disorders, which significantly increase the participant's safety risk as assessed by the investigator;
• Participants with a history of tuberculosis, or who have current symptoms, signs, imaging or laboratory evidence of active tuberculosis, or who have a positive IGRA tuberculosis infection screening test result (except the participants who have medical documented evidence of having received standardized preventive anti-tuberculosis treatment within the 5 years prior to screening);
• ALT or AST or total bilirubin levels>3×ULN at screening;
• Hb<90 g/L or PLT<80×109/L at screening;
• HBsAg positive; or HBsAg negative but HBcAb positive with HBV-DNA quantitative results exceeding the ULN defined by the local lab; HCV antibody positive with HCV-RNA quantitative results exceeding the ULN defined by the local lab; HIV antibody positive;
• HBA1C≥9.0% at screening;
• Participants who have participated in a clinical trial of any drug or medical device within 12 weeks prior to randomization and are expected to have residual effects of the investigational treatment (as determined by the investigator), or in any drug clinical trial within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to screening, or who participated in a clinical trial of oligonucleotide drugs within 1 year prior to randomization;
• Women who are pregnant or breastfeeding prior to randomization;
• Drug or alcohol abuse within 6 months prior to randomization;
• Any illness or condition that the investigator deems likely to increase the risk of the trial, affect participants adherence to the protocol or prevent them from completing it.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University First Hospital — Пекин

Идентификаторы

NCT: NCT07474636 · HS-10542-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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