Trial record 10 of 13 for:    Lupus AND Los Angeles | Open Studies

Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01946880
First received: September 13, 2013
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

This trial seeks to describe the effect of withdrawal from mycophenolate mofetil (MMF) on risk of clinically significant disease reactivation in quiescent SLE patients who have been on long-term MMF therapy. Participants who have had inactive disease for at least 24 weeks will be enrolled. Half the subjects will continue on MMF and half the subjects will be tapered off their MMF within 12 weeks. All subjects will continue hydroxychloroquine and small doses of prednisone as needed. Subject visits to assess endpoints will occur every 4 weeks from Day 0 through Week 24 and then at Weeks 32, 40, 48, and 60.


Condition Intervention Phase
Lupus Erythematosus, Systemic
Drug: Mycophenolate Mofetil
Drug: Hydroxychloroquine or Chloroquine
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Investigator-Initiated, Phase II, Randomized, Withdrawal Study of Mycophenolate Mofetil (MMF) in Patients With Stable, Quiescent Systemic Lupus Erythematosus (SLE)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • The proportion of subjects in each arm experiencing clinically significant disease reactivation. [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]

    Clinically significant SLE reactivation requires both:

    1. A SELENA-SLEDAI*-defined mild/moderate or severe flare and
    2. Increased immunosuppressive therapy on a sustained basis


Secondary Outcome Measures:
  • Time to clinically significant disease reactivation [ Time Frame: Up to week 60 ] [ Designated as safety issue: Yes ]
  • Aggregate of proportion of subjects with any SELENA-SLEDAI flare and proportion of subjects with any severe SELENA-SLEDAI* flare [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]
    Defined by disease manifestation (renal disease / extra-renal disease) and by baseline MMF dosing group (≤ 2000 mg per day / > 2000 mg per day).

  • Time from initiation of withdrawal to first SELENA-SLEDAI* flare and time to first severe SELENA-SLEDAI* flare [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with any BILAG A flare [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects in the renal subgroup with BILAG* Renal A flare [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]
  • Change in SLICC/DI [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: Yes ]
  • Change in SLICC/DI [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
  • Change in SLICC/DI [ Time Frame: Baseline to Week 60 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with aggressive adjunctive therapy added to MMF [ Time Frame: Week 60 ] [ Designated as safety issue: Yes ]
    Proportion of subjects with aggressive adjunctive therapy added to MMF (including IV immunoglobulin or rituximab) or change in MMF therapy to cytotoxic drug (e.g., cyclophosphamide) due to flare.

  • Cumulative systemic steroid dose [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
  • Change in FACIT fatigue score [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Change in FACIT fatigue score [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change in FACIT fatigue score [ Time Frame: Baseline to Week 60 ] [ Designated as safety issue: No ]
  • Change in Lupus QoL-US [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Change in Lupus QoL-US [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Change in Lupus QoL-US [ Time Frame: Baseline to Week 60 ] [ Designated as safety issue: No ]
  • Time to improvement in BILAG from maximum level during flare [ Time Frame: Maximum BILAG score during clinically significant disease reactivation to BILAG improvement up to week 60 ] [ Designated as safety issue: No ]
  • Time to recovery of baseline BILAG scores [ Time Frame: Clinically significant disease reactivation to recovery of baseline BILAG scores or BILAG C, whichever is worse, up to week 60 ] [ Designated as safety issue: No ]
  • Cumulative excess systemic steroid dose [ Time Frame: From time of clinically significant disease reactivation to return to pre-flare dose or week 60 ] [ Designated as safety issue: No ]
  • Time to return to pre-flare steroid dose [ Time Frame: clinically significant disease reactivation (flare) to pre-flare steroid dose or week 60 ] [ Designated as safety issue: No ]
  • Amount of SLE Related Grade 3-5 adverse events [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
    As defined by the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) system, which are defined as possibly, probably, or definitely related to SLE.

  • Amount of MMF related Grade 3-5 adverse events [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
    As defined by the NCI-CTCAE system, which are defined as possibly, probably, or definitely related to MMF.

  • Amount of all NCI-CTCAE Grade 3-5 adverse events. [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
  • Amount of serious adverse events. [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
  • Frequency of malignancies [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
  • Amount of NCI-CTCAE Grade 3-5 hematological events. [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
  • Total incidence of mortality possibly, probably, or definitely related to SLE. [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]
  • Total incidence of all-cause mortality [ Time Frame: Up to Week 60 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: November 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mycophenolate Mofetil Withdrawal
These subjects will taper off MMF per the protocol-specified schedule over 12 weeks and remain off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation is met, whichever comes first).
Drug: Mycophenolate Mofetil
Subjects will enter the trial on 1000-3000 mg/day of MMF and will be randomized to remain on MMF treatment or to be tapered off MMF within 12 weeks.
Other Name: MMF
Drug: Hydroxychloroquine or Chloroquine
Subjects will be on concurrent anti-malarial agents (hydroxychloroquine or chloroquine). Hydroxychloroquine is approved by the FDA for the treatment of SLE. Hydroxychloroquine has been shown to help prevent flare in SLE, and to improve skin and musculoskeletal activity in particular [7, 8]. Even lupus nephritis outcomes appear improved on a background of hydroxychloroquine therapy
Drug: Prednisone
Once the subject is randomized into the trial, the prednisone (or other corticosteroid) dose must be stable through Week 36 (24 weeks following protocol taper of MMF), in the absence of flares as described in Section 3.2, Description of Primary Endpoint. Further taper of prednisone after that point is by the investigator's discretion based on the subject's clinical status.
Active Comparator: Mycophenolate Mofetil Maintenance
These subjects will continue MMF treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Drug: Mycophenolate Mofetil
Subjects will enter the trial on 1000-3000 mg/day of MMF and will be randomized to remain on MMF treatment or to be tapered off MMF within 12 weeks.
Other Name: MMF
Drug: Hydroxychloroquine or Chloroquine
Subjects will be on concurrent anti-malarial agents (hydroxychloroquine or chloroquine). Hydroxychloroquine is approved by the FDA for the treatment of SLE. Hydroxychloroquine has been shown to help prevent flare in SLE, and to improve skin and musculoskeletal activity in particular [7, 8]. Even lupus nephritis outcomes appear improved on a background of hydroxychloroquine therapy
Drug: Prednisone
Once the subject is randomized into the trial, the prednisone (or other corticosteroid) dose must be stable through Week 36 (24 weeks following protocol taper of MMF), in the absence of flares as described in Section 3.2, Description of Primary Endpoint. Further taper of prednisone after that point is by the investigator's discretion based on the subject's clinical status.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able and willing to give written informed consent and comply with requirements of the study.
  2. Age 18 - 65 years, inclusive, at randomization.
  3. Diagnosis of SLE, per ACR criteria [32].
  4. m-SLEDAI score < 4 at screening visit (SLEDAI score without serologies).
  5. Physician Global Assessment (0-3) score of 1 or less at screening visit.
  6. On a stable dose of MMF (1000-3000 mg/day) for at least 12 weeks prior to randomization.
  7. Total duration of stable or decreasing MMF therapy must be at least

    1. two years for subjects initiating MMF for renal indications (with or without concurrent extra-renal manifestations), or
    2. one year for subjects initiating MMF for extra-renal indications.
  8. If the subject is on prednisone or other corticosteroid, the following criteria must be met:

    1. the dose may not exceed 10 mg/day (or its equivalent) for the 12 weeks prior to randomization. However, temporary (up to 4 total days) increases, not to exceed 20mg/day, are permitted.
    2. the dose must be held stable for the four weeks prior to randomization (no temporary increases within 4 weeks of randomization are permitted).
  9. If the subject has a history of B cell depleting therapy, presence of CD19 positive cells must be documented.
  10. On maintenance HCQ or chloroquine at a stable dose for at least 12 weeks prior to randomization.

Exclusion Criteria:

  1. A history of life-threatening neuropsychiatric SLE within 1 calendar year prior to randomization.
  2. Any of the following laboratory abnormalities at the screening visit:

    1. Proteinuria as defined by a spot protein/creatinine ratio > 1.0 mg/mg;
    2. Serum creatinine > 2.0 mg/dL;
    3. Transaminases > 2.5x the upper limit of normal (ULN);
    4. Hemoglobin < 9 g/dL, unless the subject has documented hemoglobinopathy;
    5. White blood count (WBC) < 2000/mm3 (equivalent to < 2 x109/L);
    6. Neutrophils < 1000/mm3 (equivalent to < 1 x109/L);
    7. Platelet count < 75,000/mm3 (equivalent to < 75 x 109/L).
  3. Prednisone > 25 mg/day (or its equivalent) within 24 weeks prior to randomization for lupus activity.
  4. Concomitant immunosuppressants including but not limited to azathioprine, methotrexate, 6-mercaptopurine, leflunomide, calcineurin inhibitors, anti-tumor necrosis factor agents within 12 weeks prior to randomization.
  5. Plasmapheresis or IV immunoglobulin within 12 weeks prior to randomization.
  6. Cyclophosphamide therapy within 24 weeks prior to randomization.
  7. Concomitant therapy with belimumab within 24 weeks prior to randomization.
  8. B cell depleting therapy within two calendar years of randomization.
  9. Experimental therapy within the 24 weeks, or five half-lives of the agent, whichever is longer, prior to randomization.
  10. Solid organ or stem cell transplantation.
  11. Identified definitive diagnosis of another autoimmune disease that may require immunosuppression for treatment, including but not limited to: rheumatoid arthritis, scleroderma, primary Sjogren's syndrome, primary vasculitis, psoriasis, multiple sclerosis, ankylosing spondylitis, and inflammatory bowel disease.
  12. Chronic infections including, but not limited to, human immunodeficiency virus (HIV), active tuberculosis (TB, currently receiving therapy), hepatitis B or hepatitis C, or latent systemic fungal infection.
  13. History of or current positive purified protein derivative (PPD) (> 5 mm induration regardless of prior Bacillus Calmette-Guérin (BCG) vaccine administration) or positive or indeterminate QuantiFERON®, or historical chest x-ray without documentation of completed treatment for either TB infection or chemoprophylaxis for TB exposure.
  14. History of malignancy within the last five years, except for resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I.
  15. Pregnant or lactating, or intention to pursue pregnancy within three months after the completion of the study.
  16. Unwilling or unable to use reliable, barrier method(s) of contraception, intrauterine devices (IUDs), or surgical sterilization from four weeks prior to randomization to three months after completion of the study in subjects of reproductive potential (males and females). Subjects who are on oral contraceptives will be advised about their potential decreased effectiveness while concurrently taking MMF.
  17. Drug or alcohol abuse within one calendar year of randomization.
  18. Other medical or psychiatric conditions that the investigator feels would place the subject at special risk by participation in this protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01946880

Contacts
Contact: Toi Thompson, MPH 773-702-8741 tthompson@medicine.bsd.uchicago.edu

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Erin Avila    310-360-9197    eavila@wallacemedical.com   
Principal Investigator: Daniel Wallace, MD         
UCSD Not yet recruiting
San Diego, California, United States, 92093-0943
Contact: Yuquan (Julia) He, CCRC    858-657-7048    y1he@ucsd.edu   
Principal Investigator: Kenneth Kalunian, MD         
UCSF School of Medicine Recruiting
San Francisco, California, United States, 94143-0633
Contact: Anne Marie Duhme, RN    415-502-1886    AnneMarie.Duhme@ucsf.edu   
Principal Investigator: Maria Dall'Era, MD         
United States, Florida
University of Miami Hospitals and Clinics Recruiting
Miami, Florida, United States, 33136
Contact: Jacqueline Vassallo    305-243-4691    JVassall@med.miami.edu   
Principal Investigator: Gabriel Contreras, MD, MPH         
Sub-Investigator: Maria Carpintero, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30303
Contact: Karla Caylor, BSN, RN    404-616-7553    kcaylor@emory.edu   
Principal Investigator: Sung Sam Lim, MD, MPH         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637-1426
Contact: Toi Thompson, MPH    773-702-8741    tthompson@medicine.bsd.uchicago.edu   
Principal Investigator: Tammy Utset, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Courtney Graft    734-936-5562    ccgraft@umich.edu   
Principal Investigator: W. J. McCune, MD         
United States, New York
Feinstein Institute for Medical Research Recruiting
Manhasset, New York, United States, 11025
Contact: Sanita Kandasami    516-562-2401    skandasami@nshs.edu   
Principal Investigator: Cynthia Aranow, MD         
Weill Cornell Medical College: Hospital for Special Surgery - Rheumatology Division Recruiting
New York, New York, United States, 10021
Contact: Glendalee Ramon    212-774-2808    ramong@hss.edu   
Contact: JoAnn Vega    212-774-2795    VegaJ@hss.edu   
Principal Investigator: Doruk Erkan, MD         
Sub-Investigator: Cassyanne Aguiar, MD         
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Maria Allen    585-275-7167    Maria_Allen@urmc.rochester.edu   
Principal Investigator: R. John Looney, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Edna Scarlett    919-684-6150      
Principal Investigator: Megan E. B. Clowse, MD, MPH         
United States, Ohio
The Ohio State University Recruiting
Columbus,, Ohio, United States, 43210
Contact: Sarah Hasselbach    614-293-5081    sarah.hasselbach@osumc.edu   
Contact: Mindy Bowers    614-293-5505    mindy.bowers@osumc.edu   
Principal Investigator: Brad H. Rovin, MD         
Sub-Investigator: Samir Parikh, MD         
United States, Oklahoma
Oklahoma Medical Research Foundation Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Fredonna Carthen    405-271-7805 ext 5      
Principal Investigator: Eliza Chakravarty, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States
Contact: Maggie Harding    843-792-8613    hardinm@musc.edu   
Principal Investigator: Diane Kamen, MD         
Sub-Investigator: Jim Oates, MD         
United States, Texas
Baylor Research Institute Not yet recruiting
Dallas, Texas, United States, 75231
Contact: Krystine Cethoute    214-987-1249    Krystine.Cethoute@baylorhealth.edu   
Principal Investigator: John J. Cush, MD         
Sponsors and Collaborators
Investigators
Study Chair: Tammy Utset, MD, MPH University of Chicago
Study Chair: Eliza Chakravarty, MD Oklahoma Medical Research Foundation
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01946880     History of Changes
Other Study ID Numbers: DAIT ALE06
Study First Received: September 13, 2013
Last Updated: July 15, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Mycophenolic Acid
Mycophenolate mofetil
Hydroxychloroquine
Chloroquine
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antibiotics, Antineoplastic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 01, 2014