2024-513864-24-00招募中2 期
A Phase II Study with Sevuparin in Subjects with Chronic Kidney Disease
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Part 1: Pharmacokinetic parameters including observed maximal plasma concentration (Cmax), time of maximum observed plasma concentration (tmax), AUC from time zero to the last quantifiable concentration (AUC0-tlast), AUC from time zero to infinity (AUC0-∞), terminal elimination half-life (t1/2λz) and renal clearance (CLR).
研究概览
简要总结
Part 1: To develop a nomogram to correlate glomerular filtration rate (GFR) to pharmacokinetic (PK) parameters to allow individualised dosing in Part 2 based on GFR. Part 2: To evaluate the change from baseline of key haematological and biochemical parameters related to anaemia and kidney function, following multiple SC doses of sevuparin in subjects with CKD.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- A Phase Ii Study With Sevuparin In Subjects With Chronic Kidney Disease
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Both healthy volunteers and patients: Signed informed consent prior to any study specific procedure.
- •For healthy volunteers only: Healthy male and female subjects aged between 18 and 55 years (inclusive) at Screening.
- •For both healthy volunteers and patients: Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
- •For healthy volunteers only: No clinically relevant findings on the physical examination at Screening.
- •Both healthy volunteers and patients: Body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive) at Screening and body weight of at least 50 kg.
- •For both healthy volunteers and patients: Contraception measure as per the CTFG guidance.
- •For patients only: Subjects will be males and females of any racial or ethnic origin aged 18-
- •For patients only: Moderate renal impairment with CKD Stage 3 (eGFR 30-44 mL/min/1.73m2) or severe renal impairment (Stage 4, eGFR 15-29 mL/min/1.73m2 or Stage 5, eGFR 15-29 mL/min/1.73m2 or requiring haemodialysis or peritoneal dialysis).
- •For patients only: Stable drug regimen defined as not starting a new drug or changing dosage within seven days or five half-lives before Day 1 of the study.
排除标准
- •For both healthy volunteers and patients: Pregnant or lactating women.
- •For patients only: Renal allograft recipients. Urinary incontinence without catheterization. Subjects with significant hepatic, cardiac, or pulmonary disease or subjects who are clinically nephrotic.
- •For patients only: Screening AST, ALT, GGT ≥2.0 × upper limit of normal; international normalized ratio (INR) >1.4; platelet count <75,000/μL. Total bilirubin level 1.5 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible provided the direct bilirubin level is not greater than 0.5 mg/dL. Supine blood pressure and pulse >160/90 mmHg and 100 bpm, respectively, or <90/45 mmHg and 50 bpm, respectively, confirmed upon triplicate measurements.
- •For patients only: Current use of coumarins including warfarin, anti-coagulation factor concentrates, chronic/subchronic use of unfractionated heparin or low molecular weight heparins (LMWH) unless in conjunction with haemodialysis treatment. Use of diuretics, renin-angiotensin system (RAS) blockers, angiotensin-converting-enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) unless at a stable dose for at least 3 months prior to enrolment.
- •For both healthy volunteers and patients: Clinically significant history of any drug sensitivity, drug allergy, heparin-induced thrombocytopenia or food allergy, as determined by the Investigator.
- •For healthy volunteers only: No clinically relevant findings in clinical laboratory tests (haematology including reticulocytes, clinical chemistry, coagulation, urinalysis) at Screening.
- •For healthy volunteers only: Positive results from urine drug screen, urine cotinine, and urine alcohol tests at Screening and pre-dose on Day
- •Positive screening test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or anti-HIV 1 and 2 antibodies.
- •For healthy volunteers only: Serum or plasma potassium <3.5 or >5.2 mEq/L at screening. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 × ULN or total bilirubin >1.5 × ULN at screening. Gilbert’s syndrome. Any repeated laboratory abnormality considered by Investigator to be clinically significant.
- •For healthy colunteers only: Mean systolic blood pressure <90 mmHg or >140 mmHg, after at least 5 minutes rest in a supine position at Screening or pre-dose at Day
- •Clinically significant ECG abnormality, as judged by the Investigator at Screening. In addition, any subject any one of the following ECG abnormalities (based on the average of the triplicate results) will be excluded: i. Uncorrected QT-interval >500 ms. ii. QTcF >470 ms. iii. QRS interval >130 ms. iv. PR interval >220 ms. eGFR by CKD-EPI >80 mL/min/m
- •For healthy volunteers only: Clinically relevant history or presence of rhythm disorders (e.g., sinoatrial heart block, second- or third-degree atrioventricular block, long QT syndrome, symptomatic bradycardia, atrial flutter, or atrial fibrillation), clinically relevant history of hypokalaemia, congestive heart failure or structural heart disease.
- •For healthy volunteers only: Clinical evidence of significant or unstable medical illness including neurological, haematological (including von Willebrand disease and heparin-induced thrombocytopenia, HIT), hepatic, pulmonary, metabolic, gastrointestinal, renal, psychiatric, endocrine or infectious diseases or malignancies. Subjects who have had splenectomy.
- •For healthy volunteers only: History or clinical evidence of any disease and/or existence of any surgical or medical condition, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment. Acute, ongoing, recurrent, or chronic systemic disease that may to interfere with the evaluation of the study results.
- •For both healthy volunteers and patients: Any relevant condition, behaviour, laboratory value or concomitant medication which, in the opinion of the investigator, makes the subject unsuitable for entry into the study.
结局指标
主要结局
Part 1: Pharmacokinetic parameters including observed maximal plasma concentration (Cmax), time of maximum observed plasma concentration (tmax), AUC from time zero to the last quantifiable concentration (AUC0-tlast), AUC from time zero to infinity (AUC0-∞), terminal elimination half-life (t1/2λz) and renal clearance (CLR).
Part 1: Pharmacokinetic parameters including observed maximal plasma concentration (Cmax), time of maximum observed plasma concentration (tmax), AUC from time zero to the last quantifiable concentration (AUC0-tlast), AUC from time zero to infinity (AUC0-∞), terminal elimination half-life (t1/2λz) and renal clearance (CLR).
Part 2: Assessment of safety parameters including type and severity of adverse events (AEs), electrocardiograms (ECGs), vital signs, clinical laboratory evaluations (serum biochemistry, haematology including reticulocytes and coagulation parameters), urinalysis (dipstick) and physical examinations.
Part 2: Assessment of safety parameters including type and severity of adverse events (AEs), electrocardiograms (ECGs), vital signs, clinical laboratory evaluations (serum biochemistry, haematology including reticulocytes and coagulation parameters), urinalysis (dipstick) and physical examinations.
次要结局
- Part 1: Assessment of the change from baseline in serum hepcidin. • Assessment of safety parameters including type and severity of AEs, ECGs, vital signs, physical examinations, and clinical laboratory evaluations i.e., serum biochemistry, haematology (including reticulocytes and coagulation parameters) and urinalysis (dipstick).
- Part 2: Assessment of the change from baseline in serum hepcidin. Assessment of the change from baseline in haemoglobin (Hb), haematocrit (b-Ht), and reticulocyte haemoglobin (b-RetHb) in blood and serum creatinine (s-Crea). Assessment of PK parameters including Cmax, tmax, AUC0-tlast, AUC0-∞, t1/2λz, plasma accumulation ratio for Cmax and AUC, time to steady state.
研究者
John Öhd
Scientific
Modus Therapeutics AB
研究点 (2)
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