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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CellCept daily & ACTHar gel biw | Active Comparator | Patients will be treated with CellCept 3 grams daily and ACTHar gel 80 U biw for 3 months per Aim 1. 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. |
|
| CellCept daily & ACTHar gel qod | Active Comparator | 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 per Aim 2. 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CellCept | Drug | For both arms: CellCept 3 grams daily, oral, from Week 0-24 CellCept 2 grams daily, oral, from Week 25-144 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With a Complete Response (CR) | Complete response (CR) is defined as all of the following criteria having been achieved:
| 6 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Responders | Responders = Complete 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 | 6 Months |
| Number of Patients With Extra-renal Flares |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Urinary Lymphocytes | Urinary markers of active inflammatory nephritis | Upon study completion, up to 30 months |
| Mean Cortisol Levels | Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm |
Inclusion Criteria:
Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR)/SLICC criteria
Age ≥ 16 years
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
Ability to provide informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anca D Askanase, MD, MPH | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University - Herbert Irving Pavilion | New York | New York | 10032 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11838846 | Background | Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002 Feb;29(2):288-91. | |
| 16273796 | Background | Lam GK, Petri M. Assessment of systemic lupus erythematosus. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S120-32. |
| Label | URL |
|---|---|
| CUMC Rheumatology Research Website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | CellCept Daily & ACTHar Gel BIW (Two Times Per Week) | Patients will be treated with CellCept 3 grams daily and ACTHar gel 80 U BIW for 3 months per Aim 1. 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. |
| FG001 | CellCept Daily & ACTHar Gel TIW (Three Times Per Week) | Patients will be treated with CellCept 3 grams daily for 3 months, and ACTHar gel 80 U TIW for the first month and ACTHar gel 80 U BIW for the following 2 months per Aim 2. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | CellCept Daily & ACTHar Gel BIW (Two Times Per Week) | Patients will be treated with CellCept 3 grams daily and ACTHar gel 80 U BIW for 3 months per Aim 1. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With a Complete Response (CR) | Complete response (CR) is defined as all of the following criteria having been achieved:
| Posted | Count of Participants | Participants | 6 Months |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CellCept Daily & ACTHar Gel BIW (Two Times Per Week) | Patients will be treated with CellCept 3 grams daily and ACTHar gel 80 U BIW for 3 months per Aim 1. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Extra-renal flare | General disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Renal flare | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anca Askanase MD, MPH | Columbia University | 212 305 0856 | ada20@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 3, 2024 | Mar 4, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008181 | Lupus Nephritis |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D009173 | Mycophenolic Acid |
| D000324 | Adrenocorticotropic Hormone |
| ID | Term |
|---|---|
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| ACTHar gel | Drug | Arm 1: 80 U biw, subcutaneous, for 3 months. Optionally additional 3 months of 80 U biw if a patient has partial response. 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. |
|
|
Frequency of extra-renal flares as defined by the SELENA-SLEDAI Flare Index. Extra-renal disease activity measured by SELENA-SLEDAI and BILAG |
| 6 Months |
| Number of Patients With Steroid -Like Side Effects | 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 | 6 Months |
| Number of Patients With Side Effects | Number of participants who experienced side effects from taking ACTHar | 6 Months |
| Upon study completion, up to 30 months |
| 6482173 | Background | Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TT, Balow JE. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int. 1984 Apr;25(4):689-95. doi: 10.1038/ki.1984.75. |
| 14717922 | Background | Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, Balow JE, Bruijn JA, Cook T, Ferrario F, Fogo AB, Ginzler EM, Hebert L, Hill G, Hill P, Jennette JC, Kong NC, Lesavre P, Lockshin M, Looi LM, Makino H, Moura LA, Nagata M; International Society of Nephrology Working Group on the Classification of Lupus Nephritis; Renal Pathology Society Working Group on the Classification of Lupus Nephritis. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb;65(2):521-30. doi: 10.1111/j.1523-1755.2004.00443.x. |
| 22722778 | Background | 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. |
| 9458022 | Background | Schweitzer EJ, Yoon S, Fink J, Wiland A, Anderson L, Kuo PC, Lim JW, Johnson LB, Farney AC, Weir MR, Bartlett ST. Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients. Transplantation. 1998 Jan 27;65(2):242-8. doi: 10.1097/00007890-199801270-00017. |
| 22087680 | Background | Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N; ALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17;365(20):1886-95. doi: 10.1056/NEJMoa1014460. |
| 9336415 | Background | Belmont HM, Levartovsky D, Goel A, Amin A, Giorno R, Rediske J, Skovron ML, Abramson SB. Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum. 1997 Oct;40(10):1810-6. doi: 10.1002/art.1780401013. |
| BG001 | CellCept Daily & ACTHar Gel TIW (Three Times Per Week) | Patients will be treated with CellCept 3 grams daily for 3 months, and ACTHar gel 80 U TIW for the first month and ACTHar gel 80 U BIW for the following 2 months per Aim 2. 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | CellCept Daily & ACTHar Gel TIW (Three Times Per Week) | Patients will be treated with CellCept 3 grams daily for 3 months, and ACTHar gel 80 U TIW for the first month and ACTHar gel 80 U BIW for the following 2 months per Aim 2. 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. |
|
|
| Secondary | Number of Responders | Responders = Complete 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 | Posted | Count of Participants | Participants | 6 Months |
|
|
|
| Secondary | Number of Patients With Extra-renal Flares | Frequency of extra-renal flares as defined by the SELENA-SLEDAI Flare Index. Extra-renal disease activity measured by SELENA-SLEDAI and BILAG | Posted | Count of Participants | Participants | 6 Months |
|
|
|
| Secondary | Number of Patients With Steroid -Like Side Effects | 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 | Posted | Count of Participants | Participants | 6 Months |
|
|
|
| Secondary | Number of Patients With Side Effects | Number of participants who experienced side effects from taking ACTHar | Posted | Count of Participants | Participants | 6 Months |
|
|
|
| Other Pre-specified | Mean Urinary Lymphocytes | Urinary markers of active inflammatory nephritis | Data was not collected due to lack of funding leading to early termination of the study. | Posted | Upon study completion, up to 30 months |
|
|
| Other Pre-specified | Mean Cortisol Levels | Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm | Data was not collected due to lack of funding leading to early termination of the study. | Posted | Upon study completion, up to 30 months |
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 1 |
| 4 |
| EG001 | CellCept Daily & ACTHar Gel TIW (Three Times Per Week) | Patients will be treated with CellCept 3 grams daily for 3 months, and ACTHar gel 80 U TIW for the first month and ACTHar gel 80 U BIW for the following 2 months per Aim 2. 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. | 0 | 4 | 1 | 4 | 0 | 4 |
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| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D008180 | Lupus Erythematosus, Systemic |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D053486 | Melanocortins |
| D011333 | Pro-Opiomelanocortin |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |