NCT06749457招募中1 期
A Phase I/IIa Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of AZD7760 in Healthy Participants and in Patients With End-stage Kidney Disease Receiving Hemodialysis Through a Central Venous Catheter
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 231
- 试验地点
- 45
- 主要终点
- Phase I: Occurence of adverse events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of AZD7760 when given as an intravenous infusion to healthy participants (Phase I) or participants with end-stage kidney disease receiving hemodialysis through a central venous catheter (Phase IIa).
详细描述
In the Phase I portion of the study, participants will be randomized to receive one of 3 dosages of AZD7760 or placebo as a single intravenous infusion.
Study details include:
- A 28-day Screening Period.
- A Dosing Period of 3 days in which a single intravenous infusion will be given on Day 1.
- A Follow-up Period of 12 months from the time of administration of the study intervention.
In the Phase IIa portion of the study, participants will be randomized to receive either AZD7760 or placebo as 2 intravenous infusions given 3 months apart.
Study details include:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must be 18 to 55 years of age (inclusive), at the time of signing the informed consent.
- •Body weight ≥ 45 kilograms (kg) and ≤ 110 kg and Body Mass Index (BMI) within the range ≥ 18.0 to ≤ 30.0 kilograms per square meter (kg/m2) (inclusive) at screening.
- •Healthy participants with no clinically significant concomitant diseases or medications (except for those specifically permitted by the protocol) according to medical history, physical examination, screening safety laboratory tests, and screening parameters, as per the judgement of the investigator.
- •Participant must be ≥ 18 years of age at the time of signing the informed consent.
- •Participants who meet all of the following disease status requirements:
- •Diagnosed with End-stage kidney disease (ESKD).
- •Requiring hemodialysis through a tunneled central venous catheter as the primary vascular access for hemodialysis.
- •Receiving hemodialysis for treatment of ESKD for at least 60 days before randomization.
- •At least 3 previous dialysis sessions using current dialyzer.
- •Receiving adequate hemodialysis based on a single-pool Kt/V measurement > 1.2 within the last 30 days.
- •No new medications have been added to the participant's regimen in the last 2 weeks prior to dosing. 'New medication' is defined as any medication that has not been prescribed or used by the participant previously (including formulation changes). Medication previously prescribed or used by the participant with dose adjustments is allowed and not considered as new medication for the purpose of this study.
- •Not taking long-term systemic antibiotics with activity against S aureus.
排除标准
- •Known hypersensitivity to any component of the study intervention
- •Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of monoclonal antibodies (mAbs).
- •Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venipuncture.
- •Aspartate Aminotransferase (AST) or alanine Aminotransferase (ALT) above 1.5 × upper limit of normal (ULN) at screening. Testing may be repeated once at the investigator's discretion.
- •Estimated glomerular filtration rate < 90 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at screening.
- •Hemoglobin or platelet count below the lower limit of normal at screening. Testing may be repeated once at the investigator's discretion.
- •White blood cell counts outside normal reference ranges unless judged by the investigator to be out of range given the known variation in white blood cell count reference interval by ethnicity. Testing may be repeated once at the investigator's discretion.
- •History of malignancy other than treated non-melanoma skin cancers or locally treated cervical cancer in the previous 5 years.
- •Any laboratory value in the screening panel that, in the opinion of the investigator, is clinically significant or might confound analysis of study results. Testing may be repeated once at the investigator's discretion.
- •Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening, as judged by the investigator.
- •Acute (time-limited) illness, including fever ≥ 38 °C (100.4 °F), one day prior to or on day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the 28-day Screening Period or may be rescreened once.
- •Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening.
- •Any condition that has the potential to increase clearance of the study intervention (eg, protein loss conditions such as severe enteropathies, or plasmapheresis).
- •Blood drawn in excess of a total of 450 milliliters (mL) (1 unit) for any reason within 2 months prior to screening.
- •Absence of suitable veins for blood sampling and administration of study intervention.
- •Any other condition that would compromise safety of the participants.
- •Any condition that, in the opinion of the investigator, might interfere with evaluation of the study intervention or interpretation of participant safety or study results.
- •Known hypersensitivity to any component of the study intervention.
- •History of allergic disease or reactions likely to be exacerbated by any component of the study intervention as listed in dose formulation section.
- •Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of mAbs.
- •Hemoglobin < 9 g/dL at screening considered by the investigator to be due to acute condition(s). Testing may be repeated once at the investigator's discretion.
- •Serum albumin of < 3 g/dL at screening considered by the investigator to be due to acute condition(s). Testing may be repeated once at the investigator's discretion.
- •Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (eg, deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 90 days prior to randomization.
- •Known S aureus infection within 90 days of study entry.
- •Known acute viral or bacterial infection or symptoms/signs consistent with such an infection within the 21 days prior to infusion or study intervention. Mild intercurrent viral illness with a temperature of 38.1 °C (100.6 °F) or less does not require exclusion, if in the judgement of the investigator this illness will not interfere with the evaluation of the mAb.
- •Participants with malignancy undergoing chemotherapy.
- •Scheduled date for living donor kidney transplant.
- •Plans to switch to peritoneal dialysis within the primary endpoint time period (181 days).
- •Regarding arteriovenous fistula (AVF) or arteriovenous graft (AVG):
- •(a) Future AVG or AVG: (i) Participants with central venous catheters currently in use for dialysis, and future plans for AVF or AVG use within 90 days of randomization are not eligible.
- •(ii) Participants with central venous catheters currently in use for dialysis, and future plans for AVF or AVG placement, but no plans for AVF or AVG use within 90 days of randomization are eligible.
- •(b) Existing AVG or AVG: (i) Participants with central venous catheters in use for dialysis, but also with an existing AVF or AVG that is not in use and with no future plans for use are eligible.
研究组 & 干预措施
Phase I: AZD7760 Dose B
Experimental
Participants will receive a single dose of AZD7760 Dose B intravenously on Day 1.
干预措施: AZD7760 (Drug)
Phase I: Placebo
Placebo Comparator
Participants will receive a single dose of placebo on Day 1.
干预措施: Placebo (Other)
Phase IIa: AZD7760 Dose D and Placebo
Experimental
Participants will receive AZD7760 Dose D and placebo on Day 1 on Day 91.
干预措施: Placebo (Other)
Phase IIa: Placebo
Placebo Comparator
Participants will receive placebo on Day 1 and on Day 91.
干预措施: Placebo (Other)
Phase I: AZD7760 Dose A
Experimental
Participants will receive a single dose of AZD7760 Dose A intravenously on Day 1.
干预措施: AZD7760 (Drug)
Phase IIa: AZD7760 Dose E
Experimental
Participants will receive AZD7760 Dose E on Day 1 and Day 91.
干预措施: AZD7760 (Drug)
Phase I: AZD7760 Dose C
Experimental
Participants will receive a single dose of AZD7760 Dose C intravenously on Day 1.
干预措施: AZD7760 (Drug)
Phase IIa: AZD7760 Dose D and Placebo
Experimental
Participants will receive AZD7760 Dose D and placebo on Day 1 on Day 91.
干预措施: AZD7760 (Drug)
结局指标
主要结局
Phase I: Occurence of adverse events (AEs)
时间窗: Day 1 to Day 181
To evaluate the safety of AZD7760 administered as a single intravenous (IV) Dose A, B, or C.
Phase I: Occurence of medically-attended adverse events (MAAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
时间窗: Day 1 to Day 361
To evaluate the safety of AZD7760 administered as a single IV Dose A, B, or C.
Phase IIa: Occurrence of AEs, MAAEs, SAEs, and AESIs
时间窗: Day 1 to Day 181
To evaluate the safety of AZD7760 compared with placebo as: * A single IV dose (at Day 1) of Dose D followed by placebo (at Day 91) * 2 IV doses (at Day 1 and Day 91) of Dose E
次要结局
- Phase I: Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)(Day 1 to Day 361)
- Phase I: Maximum observed plasma (peak) drug concentration (Cmax)(Day 1 to Day 361)
- Phase I: Time to reach peak or maximum observed concentration following drug administration (tmax)(Day 1 to Day 361)
- Phase I: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)(Day 1 to Day 361)
- Phase I: Area under plasma concentration-time curve from zero extrapolated to infinity (AUCinf)(Day 1 to Day 361)
- Phase I: Apparent volume of distribution at steady state (Vss)(Day 1 to Day 361)
- Phase I: Apparent volume of distribution at the terminal phase (Vz)(Day 1 to Day 361)
- Phase I: Incidence of ADA(Day 1 to Day 361)
- Phase IIa: Cmax(Day 181 to Day 451)
- Phase IIa: tmax(Day 181 to Day 451)
- Phase IIa: t1/2λz(Day 181 to Day 451)
- Phase IIa: AUClast(Day 181 to Day 451)
- Phase IIa: AUCinf(Day 181 to Day 451)
- Phase IIa: Vss(Day 181 to Day 451)
- Phase IIa: Vz(Day 181 to Day 451)
- Phase IIa: Incidence of anti-drug antibodies (ADAs) to AZD7760 in serum(Day 181 to Day 451)
- Phase IIa: Occurrence of AEs(Day 1 to Day 181)
- Phase IIa: Occurrence of MAAEs, SAEs, and AESIs(Day 1 to Day 451)
- Phase IIa: Cmax(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: tmax(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: t1/2λz(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: AUClast(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: AUCinf(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: Vss(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: Vz(Day 1 to Day 181 and Day 1 to Day 451)
- Phase IIa: Incidence of anti-drug antibodies (ADAs) to AZD7760 in serum(Day 1 to Day 181 and Day 1 to Day 451)
研究者
研究点 (45)
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