ACTHar in the Treatment of Lupus Nephritis

NCT02226341 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: AAAN4752
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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).

Conditions

Lupus Nephritis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Patients With a Complete Response (CR)

  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

  6 Months

Secondary Outcomes (4)

• Number of Responders

  6 Months

• Number of Patients With Extra-renal Flares

  6 Months

• Number of Patients With Steroid -Like Side Effects

  6 Months

• Number of Patients With Side Effects

  6 Months

Other Outcomes (2)

• Mean Urinary Lymphocytes

  Upon study completion, up to 30 months

• Mean Cortisol Levels

  Upon study completion, up to 30 months

Study Arms (2)

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.

Drug: CellCept; Drug: ACTHar gel

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.

Drug: CellCept; Drug: ACTHar gel

Interventions

CellCept DRUG

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

Also known as: Mycophenolate Mofetil

CellCept daily & ACTHar gel biw; CellCept daily & ACTHar gel qod

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.

Also known as: ACTHar, H.P. ACTHar Gel, Repository corticotropin

CellCept daily & ACTHar gel biw; CellCept daily & ACTHar gel qod

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University - Herbert Irving Pavilion

New York, New York, 10032, United States

Location

Related Publications (8)

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

  PMID: 11838846 BACKGROUND

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

  PMID: 16273796 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.

  PMID: 6482173 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.

  PMID: 14717922 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.

  PMID: 22722778 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.

  PMID: 9458022 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.

  PMID: 22087680 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.

  PMID: 9336415 BACKGROUND

Related Links

• CUMC Rheumatology Research Website

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Mycophenolic Acid; Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Anca Askanase MD, MPH
• Organization: Columbia University

ada20@cumc.columbia.edu

212 305 0856

Study Officials

• Anca D Askanase, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 25, 2014
• First Posted: August 27, 2014
• Study Start: October 1, 2014
• Primary Completion: January 3, 2024
• Study Completion: January 3, 2024
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-03

Locations

US (1)