Clinical Trial: ACTHar in the Treatment of Lupus Nephritis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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.

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 Summary:

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.


Sponsor: Columbia University

Current Primary Outcome: Percent of patients with a complete response (CR) [ Time Frame: 6 Months ]

Complete response (CR) is defined as all of the following criteria having been achieved:

  1. Stabilization of estimated glomerular filtration rate (eGFR) (i.e., a 6-month eGFR level ± 10% of baseline) or improvement if the screening value is changed from patient's baseline
  2. Inactive urinary sediment (red blood cells per high-power field [RBCs/HPF] < 5-10, not due to gyn bleeding)
  3. Urine protein/creatinine ratio < 0.5


Original Primary Outcome: Percent of patients with a complete response (CR) [ Time Frame: 6 Months ]

Complete response (CR) is defined as all of the following criteria having been achieved:

  1. Stabilization of estimated glomerular filtration rate (i.e., a 6-month eGFR level ± 10% of baseline) or improvement if the screening value is changed from patient's baseline
  2. Inactive urinary sediment (red blood cells per high-power field [RBCs/HPF] < 5-10, not due to gyn bleeding)
  3. Urine protein/creatinine ratio < 0.5


Current Secondary Outcome:

  • Percent responders [ Time Frame: 6 Months ]
    Frequency of responders = CR + Partial Responders (PR). PR = improvement from baseline of at least ≥ 50% in all abnormal renal parameters (proteinuria and serum creatinine) without deterioration of any measurements at 6 months
  • Percent of patients with extra-renal flares [ Time Frame: 6 Months ]
    Frequency of extra-renal flares as defined by the SELENA-SLEDAI Flare Index. Extra-renal disease activity measured by SELENA-SLEDAI and BILAG
  • Mean cortisol levels [ Time Frame: 6 Months ]
    Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm
  • Percent of patients with steroid -like side effects [ Time Frame: 6 Months ]
    Steroid -like side effects: increase in blood pressure (BP) by 20 mmHg for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), increased blood sugar with a fasting plasma glucose level ≥ 126 mg/dl, weight gain ≥ 10% of the initial weight, infections
  • Mean urinary lymphocytes [ Time Frame: 6 Months ]
    Urinary markers of active inflammatory nephritis
  • Percent of patients with side effects [ Time Frame: 6 Months ]
    Side effects from taking ACTHar


Original Secondary Outcome:

  • Percent responders [ Time Frame: 6 Months ]
    Frequency of responders = CR + Partial Responders (PR). PR = improvement from baseline of at least ≥ 50% in all abnormal renal parameters (proteinuria and serum creatinine) without deterioration of any measurements at 6 months
  • Percent of patients with extra-renal flares [ Time Frame: 6 Months ]
    Frequency of extra-renal flares as defined by the SELENA-SLEDAI Flare Index. Extra-renal disease activity measured by SELENA-SLEDAI and BILAG
  • Mean cortisol levels [ Time Frame: 6 Months ]
    Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm
  • Percent of patients with steroid -like side effects [ Time Frame: 6 Months ]
    Steroid -like side effects: increased in BP by 20 mmHg for both SBP and DBP, increased blood sugar with a fasting plasma glucose level ≥ 126 mg/dl, weight gain ≥ 10% of the initial weight, infections
  • Mean urinary lymphocytes [ Time Frame: 6 Months ]
    Urinary markers of active inflammatory nephritis
  • Percent of patients with side effects [ Time Frame: 6 Months ]
    Side effects from taking ACTHar


Information By: Columbia University

Dates:
Date Received: August 25, 2014
Date Started: October 2014
Date Completion: July 2024
Last Updated: March 17, 2016
Last Verified: March 2016