ACTH Treatment of APOL1- Associated Nephropathy

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.

Study Overview

• Status: Withdrawn
• Conditions: Kidney Disease
• Intervention / Treatment: Drug: Acthar

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Acthar 40 units; Acthar 40 units subcutaneously three times a week for patients with sub-nephrotic proteinuria.	Drug: Acthar; FDA approved drug being used in this study for sub-nephrotic proteinuria. Given Investigational New Drug (IND) exemption by FDA.; Other Names: Repository Corticotropin
Other: Acthar 80 units; Acthar 80 units subcutaneously twice a week for patients with nephrotic proteinuria.	Drug: Acthar; FDA approved drug being used in this study for sub-nephrotic proteinuria. Given Investigational New Drug (IND) exemption by FDA.; Other Names: Repository Corticotropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in proteinuria with H.C. Acthar gel	Complete remission (CR) (UPCR <0.2g/g) or partial remission (PR) (50% drop in UPCR from baseline) of proteinuria at the end of Treatment period in patients with baseline nephrotic proteinuria	End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment)
Change in proteinuria with H.C. Acthar gel	Percent change in proteinuria at the end of Treatment period in patients with baseline sub-nephrotic proteinuria	End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment)
Change in eGFR with H.C. Acthar gel	Percent change in Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR at the end of Treatment period	End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in proteinuria	Percent change in proteinuria after 1 year and 2 years of follow-up	1 year and 2 years of study follow-up after treatment completion
Percent change in CKD-EPI eGFR	Percent change in CKD-EPI eGFR at 1 and 2 years of study follow-up	1 year and 2 years of study follow-up after treatment completion
Change in CKD-EPI eGFR	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	1 year and 2 years of study follow-up after treatment completion
Duration of remission after H.C. Acthar gel treatment	Proportion of patients with baseline nephrotic proteinuria who sustained CR or PR at 1 and 2 years of study follow-up	1 year and 2 years of study follow-up after treatment completion
Changes in kidney fibrosis after H.C. Acthar gel 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	End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment)
Cholesterol and lipoprotein profile before and after treatment with H.C. Acthar gel	Changes in cholesterol and lipoprotein levels compared with baseline profiles	End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment)

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: December 4, 2013
• First Submitted That Met QC Criteria: December 4, 2013
• First Posted (Estimate): December 10, 2013

Study Record Updates

• Last Update Posted (Actual): November 7, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Hypertension; Proteinuria; AfricanAmericans; ApoL1 gene
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: IRB00024943