Impact of Acthar on Proteinuria and Disease Progression in IgA Nephropathy Patients With Nephrotic Range Proteinuria
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- To assess final protein/creatinine ratio
研究概览
简要总结
IgA nephropathy occurs when IgA-a protein that helps the body fight infections-settles in the kidneys. IgA deposits may cause the kidneys to leak blood and sometimes protein in the urine. Proteinuria (abnormal amounts of protein in urine) can be a sign of kidney damage. Current treatments for IgA nephropathy is limited to Angiotensin Converting Enzyme (ACE) inhibitor medications with fish oil. ACE Inhibitors, also called ACEI medications, slows the angiotensin converting enzyme so that blood vessels can be relaxed.
This study involves the study drugs, Acthar and Lisinopril (an ACEI medication routinely given for high blood pressure).
In previous clinical studies, some subjects with IgA nephropathy have experienced reductions in proteinuria with consistent use of Acthar. Acthar is approved by the Food and Drug Administration (FDA) and used to treat patients with proteinuria.
The purpose is to study the safety and effectiveness of the study drug Acthar given at different doses.
详细描述
Participation in this study may last up to 2 years (from first visit to final visit) and includes 10 study visits and 8 phone calls.
Subjects will be randomly assigned to one of two treatment groups:
Group A will receive Acthar 80 unit injection 2 times per week or
Group B will receive Acthar 80 unit injection 3 times per week
All participants will be prescribed Lisinopril (10mg per day or higher depending on your blood pressure) as part of regular care for their condition. If they are already on another ACEI, Lisinopril will be prescribed. If subjects are unable to tolerate Lisinopril or other ACEI medications, an angiotensin receptor blocker (ARB) will be prescribed. ARBs are another type of medication that also helps relax blood vessels if subjects cannot tolerate ACEI medications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to any study specific procedures
- •Male and females aged 18 years and older
- •BMI 40 kg/m2 or less
- •History of nephrotic syndrome due to IgA (confirmed from renal biopsy performed within last 5 years)
- •Protein to creatinine (PCR) ratio 2.5 g/g or more (spot urine)
- •Estimated GFR (eGFR) greater than 30 mL/min/1.73/m2 (as calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation as per http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm).
- •Any prior course of therapy with (but not within the last 3 months): steroids, cyclophosphamide, chlorambucil, cyclosporine or tacrolimus ). If, after f/u period, it was determined that subject did not achieve a complete or partial response, subject will be eligible for this study.
- •Antihypertensive treatment including use of Angiotensin-converting enzyme inhibitors (ACEI) and/or Angiotensin receptor blockers (ARB):
- •Unless there is a history of intolerance to ACEI or ARB therapy, the subject must be treated with at least one of these agents,
- •Treatment with ACEI and/or ARB for 3 months or more prior to Visit 1, with stable maintenance dose(s) for 30 days or more prior to Visit 1,
- •If treated with other antihypertensive therapies, treatment duration of 30 days or more and stable maintenance dose for 7 days or more prior to Visit 1; and
- •Blood pressure determined by the average of 3 or more seated readings taken 5 minutes or more apart at Visit 1:
- •Mean systolic blood pressure 140 mmHg or less and
- •Mean diastolic blood pressure 80 mmHg or less.
- •Subjects must have the following laboratory results for study inclusion:
- •Hemoglobin 9 g/dL or more
- •Platelets 100 X 10^3 cells/mu-L
- •AST 2x ULN or less
- •ALT 2x ULN or less
- •Total bilirubin 2x ULN or less
- •HgbA1c less than 6.5%
排除标准
- •Inability or refusal to give informed consent
- •Unwillingness to receive or intolerant of SC injections of study medication
- •Use of disease modifying agent within "delayed effect" 1 month of Visit 1 with: glucorticoids, cyclophosphamide, cyclosporine, cellcept
- •Therapies and/or medications:
- •History of previous use of Acthar for treatment of nephrotic syndrome
- •Prior sensitivity to Acthar or other porcine protein products
- •Planned treatment with live or live attenuated vaccines once enrolled in the study
- •Chronic systemic corticosteroid use, defined as any dose of systemic corticosteroid taken for more than 4 consecutive weeks within 1 month prior to Visit 1 (use of topical, inhaled, or intra-articular corticosteroids is allowed)
- •Planned treatment with live or live attenuated vaccines once enrolled in the study.
- •Contraindication to Acthar per Prescribing Information*
- •For the purpose of this study: history of peptic ulcer is defined as 6 months or less prior to Visit
- •Renal target disease exclusions*
- •Out of control or severe hypertension
- •History of Systemic Lupus Erythematosus
- •Uncontrolled Type 1 or type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not an exclusion)
- •History of Deep Vein Thrombosis (DVT) 6 months or less prior to Visit 1
- •Presence of renal vein thrombosis:
- •Known current diagnosis by ultrasound, magnetic resonance imaging (MRI) or computed tomography scan
- •Signs or symptoms consistent with occurrence of acute renal vein thrombosis (hematuria in combination with flank pain and >30% unexplained acute rise in serum creatinine) with renal vein thrombosis confirmed by ultrasound, MRI or computed tomography scan
- •Reproductive status:
- •Women who are pregnant
- •Women who are breastfeeding
- •Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period, as evaluated by the Investigator (women who are not of childbearing potential are those that have a history of hysterectomy, bilateral oophorectomy, or are postmenopausal with no history of menstrual flow for 12 months or more prior to Visit 1
- •Chronic active hepatitis C or B infection
- •Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation or who are known to be positive for human immunodeficiency virus
- •Undergoing or have received therapy for solid tumor malignancy 5 years or less prior to Visit 1 (with the exception of treated and cured basal cell or treated and cured squamous cell carcinoma)
- •Undergoing or have received therapy for blood malignancy 5 years or less from Visit 1
- •Cardiovascular:
- •History of or active congestive heart failure (NYHA Functional Classification Class II through IV) on http://sscts.org/ClassificationHeartFailureNYHA.aspx
- •History of known dilated cardiomyopathy with left ventricular ejection fraction 30% or less
- •Occurrence of any of the following within 3 months of Visit 1:
- •Unstable angina
- •Myocardial infarction
- •Coronary artery bypass graft or percutaneous transluminal coronary angioplasty
- •Transient ischemic attack or cerebrovascular disease; or Unstable arrhythmia
- •Administration of any other investigational medication or participation in an interventional clinical research study within 30 days of Visit 1
- •Abuse of alcohol or other substance abuse within the 6 months prior to Visit 1 as determined by the Investigator
- •Subject is a participating Investigator, study coordinator, employee of an Investigator, or immediate family member of any of the aforementioned
研究组 & 干预措施
Acthar injection 2 times per week
Acthar 80 unit injection 2 times a week
干预措施: Acthar 80 unit injection (Drug)
Acthar injection 3 times per week
Acthar 80 unit injection 3 times a week
干预措施: Acthar 80 unit injection (Drug)
结局指标
主要结局
To assess final protein/creatinine ratio
时间窗: 12 months
次要结局
- IgA level - change from baseline to 12 months to assess final kidney histology, disease activity index, and disease status.(12 months)
- Serum Creatinine - change from baseline to 2 years to assess disease status.(2 years)
- Amount of sclerosed glomeruli - change from baseline to 12 months to assess final kidney histology and disease activity index(12 months)
- Aldosterone - change from baseline to 2 years to assess disease status.(2 years)
- Number of Inflammatory cells- change from baseline to 12 months to assess final kidney histology and disease activity index(12 months)
- Albumin - change from baseline to 2 years to assess disease status.(2 years)
- Lipid Profile - change from baseline to 2 years to assess disease status.(2 years)
- P/Cr - change from baseline to 2 years to assess disease status.(2 years)
- Percent of fibrosis (measured by trichrome staining) - change from baseline to 12 months to assess final kidney histology and disease activity index(12 months)
- Cortisol - change from baseline to 2 years to assess disease status.(2 years)
研究者
David Sheikh-Hamad
Professor (Medicine-Nephrology)
Baylor College of Medicine