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ACTHar in the Treatment of Lupus Nephritis (ACTHar)

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ClinicalTrials.gov Identifier: NCT02226341
Recruitment Status : Recruiting
First Posted : August 27, 2014
Last Update Posted : March 18, 2016
Sponsor:
Information provided by (Responsible Party):
Anca Askanase, Columbia University

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).

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: CellCept Drug: ACTHar gel Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2014
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : July 2024


Arm Intervention/treatment
Active Comparator: CellCept daily & ACTHar gel biw
Patients will be treated with CellCept 3 grams daily and ACTHar gel 80 U biw for 3 months. After 3 months, patients with complete response will stop ACTHar gel but continue CellCept 3 grams daily for another 3 months whereas patients with partial response will continue CellCept 3 grams daily and be offered the option to continue ACTHar 80 U biw for another 3 months. After 6 months, all patients will continue CellCept at a dose of 2 grams daily for another 18 months.
Drug: CellCept

For both arms:

CellCept 3 grams daily, oral, from Week 0-24 CellCept 2 grams daily, oral, from Week 25-144

Other Name: Mycophenolate Mofetil

Drug: ACTHar gel
Arm 1: 80 U biw, subcutaneous, for 3 months. Optionally additional 3 months of 80 U biw if a patient has partial response.
Other Names:
  • ACTHar
  • H.P. ACTHar Gel
  • Repository corticotropin

Active Comparator: CellCept daily & ACTHar gel qod
Patients will be treated with CellCept 3 grams daily for 3 months, and ACTHar gel 80 U qod for the first month and ACTHar gel 80 U biw for the following 2 months. After 3 months, patients with complete response will stop ACTHar gel but continue CellCept 3 grams daily for another 3 months whereas patients with partial response will continue CellCept 3 grams daily and be offered the option to continue ACTHar 80 U biw for another 3 months. After 6 months, all patients will continue CellCept at a dose of 2 grams daily for another 18 months.
Drug: CellCept

For both arms:

CellCept 3 grams daily, oral, from Week 0-24 CellCept 2 grams daily, oral, from Week 25-144

Other Name: Mycophenolate Mofetil

Drug: ACTHar gel
Arm 2: 80 U qod, subcutaneous, for 1 month, then 80 U biw, subcutaneous, for 2 months. Optionally additional 3 months of 80 U biw if a patient has partial response.
Other Names:
  • ACTHar
  • H.P. ACTHar Gel
  • Repository corticotropin




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Mean cortisol levels [ Time Frame: 6 Months ]
    Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm

  4. 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

  5. Mean urinary lymphocytes [ Time Frame: 6 Months ]
    Urinary markers of active inflammatory nephritis

  6. Percent of patients with side effects [ Time Frame: 6 Months ]
    Side effects from taking ACTHar



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT02226341


Contacts
Contact: Anca D Askanase, MD, MPH 212-305-0856 ada20@cumc.columbia.edu
Contact: Rachel A Drolet, RN, MSN, AGNP-BC 212-342-1622 rad2145@cumc.columbia.edu

Locations
United States, New York
Columbia University - Herbert Irving Pavilion Recruiting
New York, New York, United States, 10032
Contact: Pooja Mahadeshwar    212-342-9051    pm2844@cumc.columbia.edu   
Contact: Samantha C Nguyen    212-342-1587    scn2119@cumc.columbia.edu   
Sub-Investigator: Rachel A Drolet, RN, MSN, AGNP-BC         
Principal Investigator: Anca D Askanase, MD, MPH         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Anca D Askanase, MD, MPH Columbia University

Additional Information:
Publications:

Responsible Party: Anca Askanase, Associate Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT02226341     History of Changes
Other Study ID Numbers: AAAN4752
First Posted: August 27, 2014    Key Record Dates
Last Update Posted: March 18, 2016
Last Verified: March 2016

Keywords provided by Anca Askanase, Columbia University:
Lupus
Lupus Nephritis
ACTHar
Columbia
Rheumatology
CUMC
Autoimmune
SLE
Proliferative Lupus Nephritis

Additional relevant MeSH terms:
Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolic Acid
Adrenocorticotropic Hormone
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs