Clinical trial NCT02226341: ACTHar in the Treatment of Lupus Nephritis
Official title: Open-label Prospective Randomized Study to Determine the Efficacy and Safety of Two Dosing Regimens of ACTHar in the Treatment of Proliferative Lupus Nephritis.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Lupus Nephritis
Keywords: Lupus
Lupus Nephritis
ACTHar
Columbia
Rheumatology
CUMC
Autoimmune
SLE
Proliferative Lupus Nephritis
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2014-08-27
Enrollment: 8
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Systemic Lupus Erythematosus (SLE) is a disease in which the immune system attacks the healthy cells and tissues, causing inflammation that can damage organs in the body. About 50% of SLE patients experience inflammation in the kidneys. The purpose of this study is to determine the effectiveness and safety of two dosing arms of ACTHar gel in treating proliferative Lupus Nephritis (LN). This study hypothesizes that both dosing arms of ACTHar are safe and effective in treating proliferative LN (Class III and IV).

Detailed description: Systemic Lupus Erythematosus (SLE) is an autoimmune disease of unknown etiology that mainly affects females of childbearing age. The disease is characterized by immune activation and the development of autoantibodies.

About 50% of SLE patients experience inflammation of the kidneys. Lupus Nephritis (LN) is a major cause of morbidity and mortality in patients with SLE. Mycophenolate Mofetil (MMF), accompanied by Prednisone, is considered the current standard of care for LN. However, long-term use of Prednisone has many serious side effects.

ACTHar Gel is an FDA approved drug comprised of an active substance called adrenocorticotropic hormone (ACTH). ACTH belongs to an anti-inflammatory group called melanocortins and carries out its effects by binding to five different melanocortin receptors (MCRs). Specifically, ACTH binding to melanocortin 2 receptor subtype (MC2R) on the adrenal cortex stimulates the production of cortisol that reduces inflammation in the kidney. In addition to binding to melanocortin 1-5 receptor subtype (MC1-5R) and acting directly on kidney tissues, ACTH may bind to MCRs on various cell types, such as immune cells, and activate processes to protect the kidney.

This study will evaluate the most effective dose of ACTHar gel in proliferative LN (Class III and IV) when given with MMF, the standard of care LN therapy. The intent of this study is to determine the effectiveness and safety of ACTHar gel in an attempt to change the clinical care requirements regarding steroid use in treating LN.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR)/SLICC criteria
2. Age ≥ 16 years
3. Active lupus nephritis defined by:

   a. Kidney biopsy documentation of International Society of Nephrology/Renal Pathology Society (ISN/RPS) Class III or Class IV proliferative nephritis (including Class V occurring in combination with Class III or IV) within 12 months and a urine protein/creatinine ratio \>1 at time of entry to study
4. Ability to provide informed consent

Exclusion Criteria:

1. Moderately severe anemia (Hgb \< 8 mg/dL)
2. Neutropenia (\< 1,000/mm3)
3. Thrombocytopenia (platelets \< 50,000/mm3)
4. Positive purified protein derivative (PPD) test confirmed by positive Quantiferon TB gold.
5. Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis
6. Active infections that in the opinion of the investigator increase the risks to the subject.
7. Known human immunodeficiency virus (HIV) and hepatitis B or C
8. End-stage renal disease (estimated GFR clearance \< 20 mL/min/1.73 m2)
9. History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas
10. Pregnancy
11. Lactation
12. Unwillingness to use a medically acceptable form of birth control (including but not limited to a diaphragm, an intrauterine device, progesterone implants or injections, oral contraceptives, the double-barrier method, or a condom)
13. Previous failure to respond to MMF
14. Use of rituximab within the past year
15. Use of experimental therapeutic agents within the past 60 days
16. Greater than or equal to 5 times the upper limit of normal of liver function tests (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], or alkaline phosphatase)
17. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study) with the exception of diseases or conditions related to active SLE
18. Current substance abuse

Primary outcomes:
measure: Number of Patients With a Complete Response (CR)
timeFrame: 6 Months
Secondary outcomes:
measure: Number of Responders
timeFrame: 6 Months
measure: Number of Patients With Extra-renal Flares
timeFrame: 6 Months
measure: Number of Patients With Steroid -Like Side Effects
timeFrame: 6 Months
measure: Number of Patients With Side Effects
timeFrame: 6 Months
Other outcomes:
measure: Mean Urinary Lymphocytes
timeFrame: Upon study completion, up to 30 months
measure: Mean Cortisol Levels
timeFrame: Upon study completion, up to 30 months
Locations:
city: New York
country: United States
facility: Columbia University - Herbert Irving Pavilion
state: New York
Study officials:
affiliation: Columbia University
name: Anca D Askanase, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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