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Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)

Primary Purpose

Treatment Resistant Nephrotic Syndrome

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

ACTHAR gel

About this trial

This is an interventional treatment trial for Treatment Resistant Nephrotic Syndrome focused on measuring Treatment Resistance, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, lipoid nephrosis, Membranous nephropathy, IgA nephropathy, proteinuria

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult nephrotic patients, at least 18 years of age
Diagnosis of focal segmental glomerulosclerosis (FSGS), resistant or relapsing minimal change disease with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: corticosteroids and at least one other immunosuppressive regimen
Diagnosis of membranous nephropathy with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: either the "Ponticelli protocol" of alternating months of pulse steroids followed by oral steroids and then an alkylating agent with each regimen repeated for six full months of therapy or a calcineurin inhibitor, cyclosporine or tacrolimus, and at least one other therapy
Diagnosis of immunoglobulin A nephropathy (IgAN) with persistent nephrotic range proteinuria in patients on ACE inhibition or angiotension receptor blockers (ARB) therapy to reduce proteinuria
Willing and able to sign informed consent
Patients of childbearing age must agree to use birth control

Exclusion Criteria:

Patients under 18 years of age
Patients unable to sign informed consent
Patients having received rituximab or another monoclonal antibody within 6 months of the trial
Patients of childbearing age who refuse to use birth control
Patients with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73m2
Patients with other renal diseases (e.g. diabetic nephropathy, renal vascular disease) that would interfere with interpretation of the study.
Patients with comorbid conditions that would interfere with completion of the trial (malignancies, congestive heart failure (CHF), recent myocardial infarction).
Patients with known contraindications to the use of H.P. ACTHAR Gel, including: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, and allergies to pork or pork products.

Sites / Locations

Columbia University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acthar gel

Arm Description

Patients will be treated with ACTHAR gel starting with 40 units given twice weekly subcutaneously for two weeks, then 80 units given twice weekly subcutaneously afterwards for a period of up to six months.

Outcomes

Primary Outcome Measures

Significant Reduction in Proteinuria to Remission Levels During the Treatment Period (Includes Complete and Partial Remission, as Defined in the Outcome Measure Description Below)

Complete remission is defined as stable or improved renal function, serum creatinine < or = 125% baseline, with proteinuria falling <500 mg/day at month 6. Partial remission is defined as stable or improved renal function, serum creatinine < or = 125% baseline, with 50% reduction in proteinuria and final proteinuria 500-3500 mg/day at month 6.

Secondary Outcome Measures

Sustained Remissions up to 1 Year After Discontinuing Therapy

Complete remission defined as stable or improved renal function, serum creatinine < or = 125% baseline, with proteinuria falling <500 mg/day at last follow-up visit (6 to 12 months post treatment). Partial remission defined as stable or improved renal function, serum creatinine < or = 125% baseline, with 50% reduction in proteinuria and final proteinuria 500-3500 mg/day at last follow-up visit (6 to 12 months post treatment).

Full Information

NCT ID

NCT01129284

First Posted

May 21, 2010

Last Updated

March 25, 2014

Sponsor

Columbia University

Collaborators

Mallinckrodt

1. Study Identification

Unique Protocol Identification Number

NCT01129284

Brief Title

Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)

Official Title

The Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

Collaborators

Mallinckrodt

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study will examine the safety and effectiveness of ACTHAR Gel, when used to treat 15 patients diagnosed with "treatment resistant nephrotic syndrome." Nephrotic syndrome is a group of symptoms that includes low levels of protein in the blood, swelling of tissue (edema), especially around the eyes, feet and hands; and high plasma levels of cholesterol. It is caused by a variety of diseases and underlying disorders that damage the kidneys, resulting in excessive excretion of protein in the urine. These diseases damage the glomeruli, which are small blood vessels that filter wastes and excess water from the blood and pass them into the bladder as urine. As a result of protein loss in the urine, the blood is deficient in protein. Normal amounts of blood protein are needed to help regulate fluid throughout the body. Protein in the blood normally draws water from the tissues and into the bloodstream. When blood protein levels are low, the normal movement of water is reversed, and fluid is drawn from the blood and accumulates in the tissues. This excess tissue fluid causes the swelling and puffiness (edema) that is a symptom of nephrotic syndrome. Nephrotic syndrome is described as "treatment resistant" when a patient fails to achieve a sustained partial or complete remission after treatment with at least two first line therapies. The goal of this study is to determine whether injections of ACTHAR Gel (an FDA approved treatment for nephrotic syndrome) over a six month period will lead to a correction of treatment resistant nephrotic syndrome in these patients.

Detailed Description

The nephrotic syndrome is characterized by heavy proteinuria, edema, hyperlipidemia, and a thrombotic tendency. Membranous nephropathy, focal segmental glomerulosclerosis, resistant minimal change disease, and Immunoglobulin A (IgA) nephropathy (also known as Berger's disease) are the common forms of idiopathic nephrotic syndrome in adults. Asymptomatic patients with idiopathic nephrotic syndrome may be treated with ACE inhibitors and /or angiotension receptor blockers to reduce proteinuria, with statins to treat hyperlipidemia, and diuretics to control edema. Patients with large amounts of proteinuria are refractory to such treatments and often require immunosuppressive medications to promote a remission of the proteinuria and the nephrotic syndrome and to prevent progressive renal failure. All such immunosuppressives have multiple potential serious side effects. Some patients either relapse after remissions of their proteinuria or are resistant to immunosuppressive therapy. A synthetic truncated analog of ACTH has been used in patients with the nephrotic syndrome in both uncontrolled trials and in a randomized controlled trial in membranous nephropathy. In uncontrolled studies it has led to sustained remissions of the nephrotic syndrome in multiple forms of idiopathic disease including membranous nephropathy and focal segmental glomerulosclerosis (FSGS). It has also led to reduction of total cholesterol, LDL cholesterol, Lpa, and elevations of HDL cholesterol. In a controlled randomized trial in membranous nephropathy it proved equivalent to an alternating monthly regimen of corticosteroids and an alkylating agent that is widely regarded as a first line therapy for this disease. This synthetic truncated analog of ACTH is not available in the US. ACTHAR gel is a natural, highly purified, porcine ACTH which is both available in the US and FDA approved for use in the nephrotic syndrome. Although ACTHAR gel has been used to treat large numbers of patients with multiple sclerosis and infantile paralysis annually, it has, however, been used in only small numbers of patients for the indication of the nephrotic syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Treatment Resistant Nephrotic Syndrome

Keywords

Treatment Resistance, Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, lipoid nephrosis, Membranous nephropathy, IgA nephropathy, proteinuria

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Acthar gel

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ACTHAR gel

Other Intervention Name(s)

H.P. Acthar gel

Intervention Description

Primary Outcome Measure Information:

Title

Significant Reduction in Proteinuria to Remission Levels During the Treatment Period (Includes Complete and Partial Remission, as Defined in the Outcome Measure Description Below)

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Sustained Remissions up to 1 Year After Discontinuing Therapy

Description

Time Frame

Up to 1 year after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult nephrotic patients, at least 18 years of age Diagnosis of focal segmental glomerulosclerosis (FSGS), resistant or relapsing minimal change disease with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: corticosteroids and at least one other immunosuppressive regimen Diagnosis of membranous nephropathy with failure to achieve a sustained partial or complete remission of the nephrotic syndrome after therapy with at least two first line therapies: either the "Ponticelli protocol" of alternating months of pulse steroids followed by oral steroids and then an alkylating agent with each regimen repeated for six full months of therapy or a calcineurin inhibitor, cyclosporine or tacrolimus, and at least one other therapy Diagnosis of immunoglobulin A nephropathy (IgAN) with persistent nephrotic range proteinuria in patients on ACE inhibition or angiotension receptor blockers (ARB) therapy to reduce proteinuria Willing and able to sign informed consent Patients of childbearing age must agree to use birth control Exclusion Criteria: Patients under 18 years of age Patients unable to sign informed consent Patients having received rituximab or another monoclonal antibody within 6 months of the trial Patients of childbearing age who refuse to use birth control Patients with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73m2 Patients with other renal diseases (e.g. diabetic nephropathy, renal vascular disease) that would interfere with interpretation of the study. Patients with comorbid conditions that would interfere with completion of the trial (malignancies, congestive heart failure (CHF), recent myocardial infarction). Patients with known contraindications to the use of H.P. ACTHAR Gel, including: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, and allergies to pork or pork products.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gerald B Appel, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22722778

Citation

Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67. doi: 10.1159/000339287. Epub 2012 Jun 19.

Results Reference

result

PubMed Identifier

24009220

Citation

Hogan J, Bomback AS, Mehta K, Canetta PA, Rao MK, Appel GB, Radhakrishnan J, Lafayette RA. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013 Dec;8(12):2072-81. doi: 10.2215/CJN.02840313. Epub 2013 Sep 5.

Results Reference

derived

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Treatment of Resistant Nephrotic Syndrome With ACTH Gel (ACTHAR)

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