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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

Tracking Information
First Submitted Date  ICMJE August 25, 2014
First Posted Date  ICMJE August 27, 2014
Last Update Posted Date March 18, 2016
Study Start Date  ICMJE October 2014
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
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 Measures  ICMJE
 (submitted: August 25, 2014)
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
Change History Complete list of historical versions of study NCT02226341 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2016)
  • 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 Measures  ICMJE
 (submitted: August 25, 2014)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ACTHar in the Treatment of Lupus Nephritis
Official Title  ICMJE 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 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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: CellCept
    • Drug: ACTHar gel
  • 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.
    Interventions:
    • Drug: CellCept
    • Drug: ACTHar gel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 25, 2014)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date January 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02226341
Other Study ID Numbers  ICMJE AAAN4752
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Anca Askanase, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anca D Askanase, MD, MPH Columbia University
PRS Account Columbia University
Verification Date March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP