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ACTH Treatment of APOL1- Associated Nephropathy

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ClinicalTrials.gov Identifier: NCT02006849
Recruitment Status : Withdrawn (no enrollment)
First Posted : December 10, 2013
Last Update Posted : November 7, 2017
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Kidney Disease Drug: Acthar Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ACTH Treatment of APOL1- Associated Nephropathy
Study Start Date : January 2014
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
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 Name: Repository Corticotropin

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 Name: Repository Corticotropin




Primary Outcome Measures :
  1. Change in proteinuria with H.C. Acthar gel [ Time Frame: End of treatment with H.C. Acthar gel (end of 6 months or 1 year of treatment) ]
    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

  2. Change in proteinuria with H.C. Acthar gel [ Time Frame: 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

  3. Change in eGFR with H.C. Acthar gel [ Time Frame: 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 :
  1. Percent change in proteinuria [ Time Frame: 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

  2. Percent change in CKD-EPI eGFR [ Time Frame: 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

  3. Change in CKD-EPI eGFR [ Time Frame: 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

  4. Duration of remission after H.C. Acthar gel treatment [ Time Frame: 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

  5. Changes in kidney fibrosis after H.C. Acthar gel treatment [ Time Frame: 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

  6. Cholesterol and lipoprotein profile before and after treatment with H.C. Acthar gel [ Time Frame: 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



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02006849


Locations
United States, North Carolina
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
Principal Investigator: Mariana Murea, MD Wake Forest University Health Sciences

Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02006849     History of Changes
Other Study ID Numbers: IRB00024943
First Posted: December 10, 2013    Key Record Dates
Last Update Posted: November 7, 2017
Last Verified: April 2016

Keywords provided by Wake Forest University Health Sciences:
AfricanAmericans
Hypertension
Proteinuria
ApoL1 gene

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Adrenocorticotropic Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs