ACTH Treatment of APOL1- Associated Nephropathy
- Registration Number
- NCT02006849
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
The purpose of this research study is to determine if the study drug H.C. Acthar gel slows the progression of your kidney disease. This drug is a steroid-based medicine with fewer side effects than other steroids used for treatment of kidney diseases similar to APOL1 nephropathy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Non-diabetic African-American with two APOL1-risk genotypes
- Age ≥21 years
- BMI < 40 kg/m2
- Hemoglobin A1c <6.5%
- eGFR ≥30 ml/min/1.73m2
- Historical urine protein: creatinine ratio ≥ 1.0 g/g
- Strong clinical suspicion of APOL1-associated nephropathy or history of biopsy proven focal segmental glomerulosclerosis (FSGS) or focal global glomerulosclerosis (FGGS)
- Women of childbearing potential: negative serum pregnancy test at Screening and agreement to follow a medically acceptable form of contraception for the duration of Acthar administration and 4 weeks thereafter
Exclusion Criteria
- Diagnosis of diabetes mellitus and/or on pharmacologic treatment for diabetes
- Medical condition that could cause secondary FSGS
- History of sensitivity to steroids (psychosis, steroid-induced diabetes)
- Chronic systemic corticosteroid use (Prednisone or equivalent systemic steroid taken for more than 4 consecutive weeks within 6 months prior to screening). Intra-articular, inhaled, and topical steroids are not exclusion criteria.
- Contraindication to Acthar per package insert: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery (within previous 6 months), history of or the presence of peptic ulcer (within 6 months prior to Screening), adrenal insufficiency or hyperfunction.
- Acute glaucoma diagnosed ≤3 months prior to Screening
- Biopsy proven glomerular disease other than FSGS or FGGS
- Live or live attenuated vaccine received within 1 month prior to screening, or planned administration once enrolled in the study
- Uncontrolled hypertension (HTN) (≥ 180/110 mmHg) and frequent admissions (≥1 admission per 6 months interval) for hypertensive urgency or hypertensive emergency
- Unstable cardiovascular disease: history of congestive heart failure (NYHA Functional Class III-IV); history of dilated cardiomyopathy with ejection fraction < 40%; any of the following events within 3 months of screening: unstable angina, myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, transient ischemic attack or cerebrovascular accident, unstable arrhythmia
- Uncontrolled volume overload: history of moderate or severe peripheral edema; on loop diuretics ≥ 120 mg daily of furosemide or ≥ 3.0 mg daily of bumetanide or ≥ 150 mg daily of ethacrynic acid or ≥ 60 mg daily of torsemide;
- History of secondary hypertension (i.e., renal artery stenosis, primary aldosteronism or pheochromocytoma)
- Significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy of less than 1 year
- Subject is expected to initiate dialysis within 6 months
- Previous treatment on a drug being investigated for the treatment of FSGS
- Known diagnosis of Human Immunodeficiency Virus, Hepatitis B, or Hepatitis C
- Known history of a primary immunodeficiency or an underlying condition such as splenectomy that predisposes the subject to infections
- Systemic hematologic disease (e.g., hematologic malignancy, sickle cell anemia, myelodysplastic syndrome)
- Current malignancy or history of malignancy within 5 years of screening, with the exception of non-melanoma skin cancers and cervical intraepithelial neoplasia
- Treatment for any malignancy (e.g., radiation, chemotherapy, hormone therapy, or biologics) within 5 years of screening, with the exception of locally excised non-melanoma skin cancer or cervical intraepithelial neoplasia
- Pregnant or breast feeding, or might become pregnant during the study or within 4 weeks after the end of treatment
- Female of reproductive potential not willing to use highly effective methods of birth control during treatment and for 4 weeks after the end of treatment
- Currently receiving systemic antibiotics for treatment of an active infection; or history of frequent infections (more than one event per 6 months)
- History of any organ transplant
- Bipolar disorder, or Major Depressive Disorder characterized by severe depression requiring hospitalization, or history of suicidal ideation/attempts
- Currently enrolled in another interventional study, or less than 4 weeks since ending another interventional study(s) or receiving investigational agents(s)
- Subject has a disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with all required study procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Acthar 40 units Acthar Acthar 40 units subcutaneously three times a week for patients with sub-nephrotic proteinuria. Acthar 80 units Acthar Acthar 80 units subcutaneously twice a week for patients with nephrotic proteinuria.
- Primary Outcome Measures
Name Time Method Change in proteinuria with H.C. Acthar gel End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment) Percent change in proteinuria at the end of Treatment period in patients with baseline sub-nephrotic proteinuria
Change in eGFR with H.C. Acthar gel End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment) Percent change in Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR at the end of Treatment period
- Secondary Outcome Measures
Name Time Method Percent change in proteinuria 1 year and 2 years of study follow-up after treatment completion Percent change in proteinuria after 1 year and 2 years of follow-up
Percent change in CKD-EPI eGFR 1 year and 2 years of study follow-up after treatment completion Percent change in CKD-EPI eGFR at 1 and 2 years of study follow-up
Change in CKD-EPI eGFR 1 year and 2 years of study follow-up after treatment completion Change in eGFR over time, based on baseline proteinuria (nephrotic vs. sub-nephrotic), baseline eGFR (eGFR 30-45 vs. eGFR 45-59), and Acthar dose
Duration of remission after H.C. Acthar gel treatment 1 year and 2 years of study follow-up after treatment completion Proportion of patients with baseline nephrotic proteinuria who sustained CR or PR at 1 and 2 years of study follow-up
Changes in kidney fibrosis after H.C. Acthar gel treatment End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment) Modifications in kidney histopathology on second post-treatment kidney biopsy (% glomerulosclerosis, % tubulointerstitial fibrosis, restoration of podocyte markers \[e.g.,podocin, synaptopodin, Wilms tumor 1\]) compared with baseline biopsy
Cholesterol and lipoprotein profile before and after treatment with H.C. Acthar gel End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment) Changes in cholesterol and lipoprotein levels compared with baseline profiles
Trial Locations
- Locations (1)
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States