A Phase 1b Study to Evaluate the PK of CSL300 (Clazakizumab) in Chinese Subjects With End Stage Kidney Disease (ESKD)

Официальное название

A Phase 1b, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Pharmacokinetics and Safety of CSL300 (Clazakizumab) in Chinese Subjects With End Stage Kidney Disease Undergoing Dialysis

Обзор

This is a phase 1b, partial-blind (Sponsor unblinded), randomized, multicenter, placebo-controlled study. The primary objective of this study is to evaluate the pharmacokinetics (PK) of CSL300 after single and multiple doses in Chinese participants with end stage kidney disease (ESKD) undergoing dialysis.

Вмешательства

• Биопрепарат CSL300
  CSL300 is a humanized anti-interleukin 6 (anti-IL-6) monoclonal antibody (mAb).
• Другое Placebo
  Placebo is a solution for injection matching the excipient content and concentration of the CSL300 product, minus the active ingredient.

Первичные конечные точки

• Area Under the Concentration-time (AUC) Curve of CSL300 Over 1 Dosing Interval After Multiple Doses (AUC0-tau,MD) [Срок оценки: Day 85 up to Day 113]
• Trough Concentration at Steady State (Ctrough,ss) [Срок оценки: Up to Day 141]

Вторичные конечные точки (10)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Event of Special Interests (AESIs) [Срок оценки: Up to Day 225 (End of Study [EoS])]
• Percentage of Participants With TEAEs, SAEs, and AESIs [Срок оценки: Up to Day 225 (EoS)]
• Percentage of Participants With a Clinically Significant Change From Baseline in Laboratory Test Results [Срок оценки: At Baseline and up to Day 225 (EoS)]
• Number of Participants With Antidrug Antibodies [Срок оценки: At Days 1, 29, 85, and 169]
• Maximum Observed Concentration (Cmax) of CSL300 [Срок оценки: Up to Day 169]
• Area Under the Concentration-Time Curve From Time 0 to Day 28 (AUC0-28d) of CSL300 [Срок оценки: Up to Day 28]
• Trough Concentration (Ctrough) of CSL300 [Срок оценки: Up to Day 141]
• Time to Reach Cmax (Tmax) of CSL300 [Срок оценки: Up to Day 85]
• Change From Baseline on log-scale High-Sensitivity C-reactive Protein (hs-CRP) [Срок оценки: At Baseline, Week 12, and Week 24]
• Plasma Interleukin-6 (IL-6) Free and Total Levels [Срок оценки: At Weeks 12 and 24]

Критерии участия

Критерии включения

• Participants has provided written informed consent and is willing and able to adhere to all protocol requirements.
• Aged 18 or older, inclusive, at the time of providing written informed consent.
• Diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks before Screening.

Критерии исключения

• Exclusion related to risk of infection: concomitant use of systemic immunosuppressant agents, primary immunodeficiency, positive test for active tuberculosis (TB), history of latent TB without completion of full course of prophylactic treatment, evidence of human immunodeficiency virus infection during Screening, seropositivity for hepatitis B surface antigen or positive hepatitis B virus (HBV) DNA during Screening, seropositivity for hepatitis C virus ribonucleic acid during Screening, diagnosis of clinically significant active infection, history of / OR current invasive fungal infection OR other opportunistic infection OR recurrent cellulitis (defined as 2 or more episodes in the year prior to screening), administration of a live vaccine within 6 weeks of start of Screening, presence of urinary catheter, or evidence of wet gangrene or nonhealing ulcers.
• Exclusion related to laboratory abnormalities: abnormal liver function tests, neutropenia, thrombocytopenia, or significant anemia.
• Exclusion related to medical history: any life-threatening disease expected to result in death within 12 months (other than cardiovascular disease), evidence of active hepatic disease and / or moderate or severe hepatic impairment, recent unplanned hospitalization (< 30 days) prior to Screening, recent (< 3 months) major surgery or planned major surgery known at the time of Screening, poorly controlled hypertension, a present or previous (< 5 years) malignancy except for basal cell carcinoma, fully excised squamous cell carcinoma of the skin, or nonrecurrent (< 5 years of Screening) cervical carcinoma in situ, active or recent (< 30 days of Screening) clinically severe bleeding, a scheduled kidney transplant within 6 months of Screening, a history of anaphylaxis or hypersensitivity to CSL300 or any constituents of the product, or a history of demyelinating disorders.
• Exclusion related to risk of gastrointestinal perforation: a history of GI perforation, inflammatory bowel disease (except fully excised ulcerative colitis), or peptic ulcer disease (< 12 months before Screening), a history of diverticular disease or diverticulitis (except if disease has been fully excised). An incidental finding of diverticulosis (presence of small diverticula) and no history of symptoms, complications, or any episodes requiring treatment may be eligible for the study based on investigator's judgment. However, any history of complications, inflammation, or infection suggestive of diverticulitis or diverticular disease is exclusionary, inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis except if fully excised, or prior gastric bypass surgery.
• Exclusion related to treatment compliance: evidence of inadequate dialysis, unwillingness or inability to comply with study procedures, a history of noncompliance with medical treatments, or ongoing alcohol or illicit substance abuse.
• Current or recent participation in research study involving an experimental agent < 3 months of Screening.
• Pregnant, breastfeeding, or unwillingness to practice adequate contraception during the study and for 5 months after the last dose of investigational product.
• The presence of any condition that in the opinion of the Investigator would (1) compromise the safety of the participant in case of participation in the study, (2) compromise the quality of the data, and / or (3) limit the life expectancy of the participant to < 1 year.
• The Sponsor determines that the participant is no longer needed for participation in study.

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 People's Hospital — Пекин

Идентификаторы

NCT: NCT07619820 · CSL300_1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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