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ACTHar in the Treatment of Lupus Nephritis (ACTHar)

Primary Purpose

Lupus Nephritis

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

CellCept

ACTHar gel

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus, Lupus Nephritis, ACTHar, Columbia, Rheumatology, CUMC, Autoimmune, SLE, Proliferative Lupus Nephritis

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

Moderately severe anemia (Hgb < 8 mg/dL)
Neutropenia (< 1,000/mm3)
Thrombocytopenia (platelets < 50,000/mm3)
Positive purified protein derivative (PPD) test confirmed by positive Quantiferon TB gold.
Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis
Active infections that in the opinion of the investigator increase the risks to the subject.
Known human immunodeficiency virus (HIV) and hepatitis B or C
End-stage renal disease (estimated GFR clearance < 20 mL/min/1.73 m2)
History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas
Pregnancy
Lactation
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)
Previous failure to respond to MMF
Use of rituximab within the past year
Use of experimental therapeutic agents within the past 60 days
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)
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
Current substance abuse

Sites / Locations

Columbia University - Herbert Irving PavilionRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

CellCept daily & ACTHar gel biw

CellCept daily & ACTHar gel qod

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Percent of patients with a complete response (CR)

Complete response (CR) is defined as all of the following criteria having been achieved: 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 Inactive urinary sediment (red blood cells per high-power field [RBCs/HPF] < 5-10, not due to gyn bleeding) Urine protein/creatinine ratio < 0.5

Secondary Outcome Measures

Percent responders

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

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

Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm

Percent 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

Mean urinary lymphocytes

Urinary markers of active inflammatory nephritis

Percent of patients with side effects

Side effects from taking ACTHar

Full Information

NCT ID

NCT02226341

First Posted

August 25, 2014

Last Updated

March 17, 2016

Sponsor

Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT02226341

Brief Title

ACTHar in the Treatment of Lupus Nephritis

Acronym

ACTHar

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

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Recruiting

Study Start Date

October 2014 (undefined)

Primary Completion Date

January 2024 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lupus Nephritis

Keywords

Lupus, Lupus Nephritis, ACTHar, Columbia, Rheumatology, CUMC, Autoimmune, SLE, Proliferative Lupus Nephritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CellCept daily & ACTHar gel biw

Arm Type

Active Comparator

Arm Description

Arm Title

CellCept daily & ACTHar gel qod

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

CellCept

Other Intervention Name(s)

Mycophenolate Mofetil

Intervention Description

For both arms: CellCept 3 grams daily, oral, from Week 0-24 CellCept 2 grams daily, oral, from Week 25-144

Intervention Type

Drug

Intervention Name(s)

ACTHar gel

Other Intervention Name(s)

ACTHar, H.P. ACTHar Gel, Repository corticotropin

Intervention Description

Arm 1: 80 U biw, subcutaneous, for 3 months. Optionally additional 3 months of 80 U biw if a patient has partial response.

Intervention Type

Drug

Intervention Name(s)

ACTHar gel

Other Intervention Name(s)

ACTHar, H.P. ACTHar Gel, Repository corticotropin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Percent of patients with a complete response (CR)

Description

Time Frame

6 Months

Secondary Outcome Measure Information:

Title

Percent responders

Description

Time Frame

6 Months

Title

Percent of patients with extra-renal flares

Description

Frequency of extra-renal flares as defined by the SELENA-SLEDAI Flare Index. Extra-renal disease activity measured by SELENA-SLEDAI and BILAG

Time Frame

6 Months

Title

Mean cortisol levels

Description

Cortisol levels 8 hours after ACTHar dose in 2-3 patients per dosing arm

Time Frame

6 Months

Title

Percent of patients with steroid -like side effects

Description

Time Frame

6 Months

Title

Mean urinary lymphocytes

Description

Urinary markers of active inflammatory nephritis

Time Frame

6 Months

Title

Percent of patients with side effects

Description

Side effects from taking ACTHar

Time Frame

6 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: Moderately severe anemia (Hgb < 8 mg/dL) Neutropenia (< 1,000/mm3) Thrombocytopenia (platelets < 50,000/mm3) Positive purified protein derivative (PPD) test confirmed by positive Quantiferon TB gold. Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis Active infections that in the opinion of the investigator increase the risks to the subject. Known human immunodeficiency virus (HIV) and hepatitis B or C End-stage renal disease (estimated GFR clearance < 20 mL/min/1.73 m2) History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas Pregnancy Lactation 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) Previous failure to respond to MMF Use of rituximab within the past year Use of experimental therapeutic agents within the past 60 days 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) 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 Current substance abuse

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anca D Askanase, MD, MPH

Phone

212-305-0856

ada20@cumc.columbia.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Rachel A Drolet, RN, MSN, AGNP-BC

Phone

212-342-1622

rad2145@cumc.columbia.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anca D Askanase, MD, MPH

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University - Herbert Irving Pavilion

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Pooja Mahadeshwar

Phone

212-342-9051

pm2844@cumc.columbia.edu

First Name & Middle Initial & Last Name & Degree

Samantha C Nguyen

Phone

212-342-1587

scn2119@cumc.columbia.edu

First Name & Middle Initial & Last Name & Degree

Rachel A Drolet, RN, MSN, AGNP-BC

First Name & Middle Initial & Last Name & Degree

Anca D Askanase, MD, MPH

12. IPD Sharing Statement

Citations:

PubMed Identifier

11838846

Citation

Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002 Feb;29(2):288-91.

Results Reference

background

PubMed Identifier

16273796

Citation

Lam GK, Petri M. Assessment of systemic lupus erythematosus. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S120-32.

Results Reference

background

PubMed Identifier

6482173

Citation

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.

Results Reference

background

PubMed Identifier

14717922

Citation

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. Erratum In: Kidney Int. 2004 Mar;65(3):1132.

Results Reference

background

PubMed Identifier

22722778

Citation

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.

Results Reference

background

PubMed Identifier

9458022

Citation

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.

Results Reference

background

PubMed Identifier

22087680

Citation

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.

Results Reference

background

PubMed Identifier

9336415

Citation

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.

Results Reference

background

Links:

URL

http://www.rheumatologyatcolumbia.org/index-3.html

Description

CUMC Rheumatology Research Website

Learn more about this trial

ACTHar in the Treatment of Lupus Nephritis

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