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Lupus NephritisPhase 3NCT00377637

A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.

A Phase 3 study testing Mycophenolate mofetil (MMF), Cyclophosphamide and Azathioprine in people with Lupus Nephritis, run by Hoffmann-La Roche at 108 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This 2 arm study assessed the efficacy of Mycophenolate Mofetil (MMF; CellCept) compared to cyclophosphamide in inducing a response in patients with lupus nephritis, and the long term efficacy of MMF compared to azathioprine in maintaining remission and renal function. Read more about this study

Who is it for?
Ages 12 to 75 years
Conditions the study is for
Lupus Nephritis
What is being tested?
Mycophenolate mofetil (MMF), Cyclophosphamide and Azathioprine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
370 participants
Where
108 sitesin 17 countries
Study dates
Jul 2005to Mar 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • male or female patients, 12-75 years of age;
  • diagnosis of systemic lupus erythematosus;
  • kidney biopsy within 6 months of study, with histological diagnosis of lupus nephritis;
  • laboratory evidence of active nephritis.

Who cannot join

  • continuous dialysis starting >2 weeks before randomization into induction phase, and/or with an anticipated duration of >8 weeks;
  • previous or planned kidney transplant;
  • other clinically significant active medical conditions.

Trial locations and contacts

108 sites in 17 countries.

108 sites in 17 countries

United States28 sites

  • Study site

    Ann Arbor, Michigan, 48109-0358

  • Study site

    Atlanta, Georgia, 30303

  • Study site

    Baltimore, Maryland, 21205

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Brooklyn, New York, 11203

  • Study site

    Chapel Hill, North Carolina, 27599-7280

  • Study site

    Charleston, South Carolina, 29425

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Cleveland, Ohio, 44136

  • Study site

    Columbia, Missouri, 65212

  • Study site

    Columbus, Ohio, 43210

  • Study site

    Dallas, Texas, 75390

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Huntsville, Alabama, 35801

  • Study site

    La Jolla, California, 92037

  • Study site

    Lake Success, New York, 11042

  • Study site

    Los Angeles, California, 90095

  • Study site

    Miami, Florida, 33136

  • Study site

    New York, New York, 10003

  • Study site

    New York, New York, 10021

  • Study site

    New York, New York, 10032

  • Study site

    Oklahoma City, Oklahoma, 73104

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Pittsburgh, Pennsylvania, 15213

  • Study site

    San Francisco, California, 94143

  • Study site

    San Leandro, California, 94578

  • Study site

    Torrance, California, 90502

Other trials in United States

Germany12 sites

  • Study site

    Aachen, 52074

  • Study site

    Bad Bramstedt, 24576

  • Study site

    Berlin, 10117

  • Study site

    Berlin, 14059

  • Study site

    Dresden, 01307

  • Study site

    Düsseldorf, 40225

  • Study site

    Erlangen, 91054

  • Study site

    Hanover, 30625

  • Study site

    Leipzig, 04103

  • Study site

    München, 80336

  • Study site

    München, 81675

  • Study site

    Münster, 48149

Other trials in Germany

United Kingdom10 sites

  • Study site

    Birmingham, B15 2TT

  • Study site

    Cambridge, CB2 2QQ

  • Study site

    Leeds, LS1 3EX

  • Study site

    London, SE1 7EH

  • Study site

    London, W12 OHS

  • Study site

    London, WIT 4NJ

  • Study site

    Manchester, M13 9WL

  • Study site

    Newcastle upon Tyne, NE7 7DN

  • Study site

    Sheffield, S10 2JF

  • Study site

    Southampton, SO16 6YD

Other trials in United Kingdom

Spain7 sites

  • Study site

    Alicante, 03010

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 08036

  • Study site

    Madrid, 28041

  • Study site

    Málaga, 29010

  • Study site

    Santander, 39008

  • Study site

    Seville, 41013

Other trials in Spain

Canada6 sites

  • Study site

    Halifax, Nova Scotia, B3H 2Y9

  • Study site

    London, Ontario, N6A 4V2

  • Study site

    Montreal, Quebec, H1T 2M4

  • Study site

    Toronto, Ontario, M5T 2S8

  • Study site

    Vancouver, British Columbia, V5Z 1L7

  • Study site

    Victoria, British Columbia, V8Z 7X8

Other trials in Canada

France6 sites

  • Study site

    Lille, 59037

  • Study site

    Lyon, 69437

  • Study site

    Nantes, 44035

  • Study site

    Paris, 75679

  • Study site

    Paris, 75877

  • Study site

    Toulouse, 31059

Other trials in France

Argentina5 sites

  • Study site

    Buenos Aires, C1015ABO

  • Study site

    Buenos Aires, C1425DQK

  • Study site

    Córdoba, 5016

  • Study site

    San Isidro, B1602BPPD

  • Study site

    San Miguel de Tucumán, T4000AXL

Other trials in Argentina

Australia5 sites

  • Study site

    Adelaide, SA 5000

  • Study site

    Camperdown, 2050

  • Study site

    Melbourne, 3168

  • Study site

    Parkville, 3052

  • Study site

    Woodville, 5011

Other trials in Australia

China5 sites

  • Study site

    Beijing, 100034

  • Study site

    Guangdong, 510008

  • Study site

    Guangzhou, 510630

  • Study site

    Jiangsu, 210002

  • Study site

    Shanghai, 200001

Other trials in China

Italy5 sites

  • Study site

    Brescia, 25125

  • Study site

    Milan, 20149

  • Study site

    Padova, 35128

  • Study site

    Pisa, 56100

  • Study site

    Udine, 33100

Other trials in Italy

Belgium3 sites

  • Study site

    Brussels, 1200

  • Study site

    Leuven, 3000

  • Study site

    Liège, 4000

Other trials in Belgium

Brazil3 sites

  • Study site

    Rio de Janeiro, 20551-030

  • Study site

    São Paulo, 04039-020

  • Study site

    Sorocaba, 18030-210

Other trials in Brazil

Greece3 sites

  • Study site

    Athens, 11521

  • Study site

    Athens, 11527

  • Study site

    Heraklion, 71500

Other trials in Greece

Hungary3 sites

  • Study site

    Debrecen, 4032

  • Study site

    Pécs, 7632

  • Study site

    Szeged, 2724

Other trials in Hungary

Mexico3 sites

  • Study site

    Mérida, 97000

  • Study site

    Mexico City, 14000

  • Study site

    San Luis Potosí City, 78240

Other trials in Mexico

Czechia2 sites

  • Study site

    Brno, 656 91

  • Study site

    Prague, 128 08

Other trials in Czechia

Portugal2 sites

  • Study site

    Lisbon

  • Study site

    Porto, 4200-319

Other trials in Portugal

About this study

Official title: A Prospective, Randomized, Active Controlled, Parallel Group, Multi-center Trial to Assess the Efficacy and Safety of Mycophenolate Mofetil (MMF) in Inducing Response and Maintaining Remission in Subjects With Lupus Nephritis.

This 2 arm study assessed the efficacy of Mycophenolate Mofetil (MMF; CellCept) compared to cyclophosphamide in inducing a response in patients with lupus nephritis, and the long term efficacy of MMF compared to azathioprine in maintaining remission and renal function. Patients were randomized to receive either MMF (1.5 g twice daily [bid]) or cyclophosphamide (0.5-1.0 g/m^2 in monthly pulses) in the induction phase. Those patients meeting criteria for response were re-randomized for entry into the maintenance phase, to receive either MMF (1 g bid) or azathioprine (2 mg/kg/day).

Conditions
Lupus Nephritis
Being tested
Mycophenolate mofetil (MMF), Cyclophosphamide, Azathioprine, Placebo to Azathioprine, Placebo to Mycophenolate mofetil
Medical subject headings
Lupus Nephritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mycophenolate mofetil (MMF)Drug

    Also called CellCept

    Supplied as 500 mg tablets taken orally twice a day (BID). Dose specific for each arm. Dosing started at 500 mg BID for the first week, increasing by 500 mg in subsequent weeks until the final target dose was reached.

  • CyclophosphamideDrug

    Also called Endoxan®

    Intravenous cyclophosphamide (IVC) was administered every four weeks (monthly) to a total of six infusions.

    Dosing was started at 0.75 g/m^2 of body surface area for the first month, with subsequent doses at 0.5-1.0 g/m^2. The target dose was 1.0 g/m^2, but doses were titrated by 0.25 g/m^2 increments to maintain nadir leukocyte count between 2500-4000/mm^3.

  • AzathioprineDrug

    Also called Imuran®

    2 mg/kg/day orally, provided as 50 mg capsules to be taken after meals.

  • Placebo to AzathioprineDrug

    Placebo capsules matching Azathioprine taken orally once a day.

  • Placebo to Mycophenolate mofetilDrug

    Placebo tablets matching Mycophenolate mofetil taken orally twice daily.

  • CorticosteroidDrug

    Oral prednisolone (or equivalent) starting at a dose of 0.75-1.0 mg/kg/day (maximum 60 mg/day) tapered to 10 mg/day.

Study groups in NCT00377637
Study groupRoleWhat they receive
Induction Phase: Mycophenolate mofetilExperimentalParticipants received oral mycophenolate mofetil (MMF) 1.5 g twice a day and concomitant corticosteroids for the 24 weeks of the Induction Phase.
Receives: Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroid
Induction Phase: CyclophosphamideActive comparatorParticipants received monthly infusions of cyclophosphamide, 0.5 to 1.0 g per square meter of body surface area and concomitant treatment with corticosteroids for the 24 week Induction Phase.
Receives: Drug: Cyclophosphamide; Drug: Corticosteroid
Maintenance Phase: Mycophenolate mofetilExperimentalParticipants received mycophenolate mofetil (MMF) 1.0 g orally twice a day, placebo to azathioprine orally once a day and corticosteroid for the 36 weeks Maintenance Phase.
Receives: Drug: Mycophenolate mofetil (MMF); Drug: Placebo to Azathioprine; Drug: Corticosteroid
Maintenance Phase: AzathioprineActive comparatorParticipants received azathioprine (AZA) 2 mg/kg/day orally once a day, placebo to mycophenolate mofetil orally twice a day and corticosteroid for the 36 weeks Maintenance Phase.
Receives: Drug: Azathioprine; Drug: Placebo to Mycophenolate mofetil; Drug: Corticosteroid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Induction Phase: Number of Patients Showing Treatment Response

    Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to <3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria <3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.

    Measured: 24 weeks

  2. Maintenance Phase: Kaplan-Meier Estimates of Percentage of Participants Treatment Failure Free, by Time Interval

    Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.

    Measured: From the start of the Maintenance Phase to Month 36

Secondary outcomes (12)

  1. Induction Phase: Number of Participants Achieving Complete Remission

    Number of participants achieving complete remission as defined by return to normal serum creatinine, proteinuria ≤500 mg/24 hours and an inactive urinary sediment (absence of red blood cells, white blood cells or cellular or granular casts) after 24 weeks.

    Measured: 24 weeks

  2. Induction Phase: Change From Baseline to Week 24 in Serum Creatinine

    Measured: Baseline, Week 24

  3. Induction Phase: Change From Baseline to Week 24 in 24-hour Urine Protein

    24-hour urine protein was measured at Baseline and Week 24.

    Measured: Baseline, Week 24

  4. Induction Phase: Change From Baseline to Week 24 in Serum Albumin

    Measured: Baseline, Week 24

  5. Induction Phase: Change in Renal British Isles Lupus Assessment Group (BILAG) Score

    BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system. The BILAG individual system summaries were calculated by a program supplied by ADS-Limathon (Sheffield, UK).

    The score at baseline was compared to the score at the 24 week endpoint for each treatment group, reported here for the renal system.

    Measured: Baseline, 24 weeks

  6. Induction Phase: Change From Baseline in Short-Form Health Survey (SF-36) Domain and Component Scores

    The SF-36 is a 36 item quality of life questionnaire. The short-form version has eleven questions that permit the participant to rate how they feel that particular day. The SF-36 consists of eight scaled scores and two component scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score with the higher scores indicating better quality of life.

    Measured: Baseline and 24 weeks

  7. Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Deaths

    Treatment Failure was adjudicated by a clinical endpoints committee (CEC) and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis (LN).

    Measured: From the start of the Maintenance Phase to Month 36

  8. Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With End-stage Renal Disease (ESRD)

    Time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), was defined as any 1 the following: death, ESRD, sustained doubling of serum creatinine, renal flare (proteinuric or nephritic), or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. ESRD is defined as progression to chronic hemodialysis or renal transplant.

    Measured: From the start of the Maintenance Phase to Month 36

  9. Maintenance Phase: Events Contributing to the Primary Endpoint: Number of Participants With Sustained Doubling of Serum Creatinine

    Sustained doubling of serum creatinine concentration is defined as the first serum creatinine value that is twice the mean of the lowest 2 values from screening to end of induction, as confirmed by a second serum creatinine value obtained at least 4 weeks after the initial doubling.

    Measured: From the start of the Maintenance Phase to Month 36

  10. Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Renal Flare Free, by Time Interval

    A proteinuric flare is defined as a doubling of the urine protein:creatinine ratio, and proteinuria ≥1 g/24 h in patients with urine protein ≤0.5 g/24 h at the end of the induction phase, or proteinuria ≥2 g/24 h if urine protein was >0.5 g/24 h at the end of the induction phase. A nephritic flare is defined as a 25% increase in serum creatinine accompanied by 1 or more of the following: (a) simultaneous doubling of the proteinuria reaching a minimum of 2 g/24 h (b) new/increased hematuria or (c) the appearance of cellular casts. All flares were adjudicated by a clinical endpoints committee.

    Measured: From the start of the Maintenance Phase to Month 36

  11. Maintenance Phase: Events Contributing to the Primary Endpoint: Kaplan-Meier Estimates of Percentage of Participants Not Receiving Rescue Therapy

    The primary efficacy parameter was the time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), defined as any of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to rescue treatment for each patient. The data presented are the percentage of participants who were rescue treatment free at each time interval as estimated by Kaplan-Meier.

    Measured: From the start of the Maintenance Phase to Month 36

  12. Maintenance Phase: Participants With Major Extra-renal Flare

    A major extra-renal flare is defined as a British Isles Lupus Assessment Group (BILAG) Score category A in one extrarenal organ or three organs with concurrent category B scores. BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system.

    Measured: From the start of the Maintenance Phase to Month 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2006 (estimated)
  2. Study startJul 2005
  3. Primary completionMar 2007
  4. Study completionMar 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
370 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00377637
Sponsor's protocol ID
WX17801
Status last verified
Oct 2011
First submitted
15 Sep 2006
Last updated
6 Dec 2011

Publications

  • Sundel R, Solomons N, Lisk L; Aspreva Lupus Management Study (ALMS) Group. Efficacy of mycophenolate mofetil in adolescent patients with lupus nephritis: evidence from a two-phase, prospective randomized trial. Lupus. 2012 Nov;21(13):1433-43. doi: 10.1177/0961203312458466. Epub 2012 Aug 24.

    PubMed 22922564

  • 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.

    PubMed 22087680

  • Dall'Era M, Stone D, Levesque V, Cisternas M, Wofsy D. Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide. Arthritis Care Res (Hoboken). 2011 Mar;63(3):351-7. doi: 10.1002/acr.20397. Epub 2010 Nov 15.

    PubMed 21080348

  • Ginzler EM, Wofsy D, Isenberg D, Gordon C, Lisk L, Dooley MA; ALMS Group. Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum. 2010 Jan;62(1):211-21. doi: 10.1002/art.25052.

    PubMed 20039429

  • Isenberg D, Appel GB, Contreras G, Dooley MA, Ginzler EM, Jayne D, Sanchez-Guerrero J, Wofsy D, Yu X, Solomons N. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study. Rheumatology (Oxford). 2010 Jan;49(1):128-40. doi: 10.1093/rheumatology/kep346. Epub 2009 Nov 20.

    PubMed 19933596

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mycophenolate mofetil (MMF), Cyclophosphamide and Azathioprine in people with Lupus Nephritis, run by Hoffmann-La Roche at 108 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 108 sites in United States, Germany, United Kingdom, Spain, Canada and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Induction Phase: Number of Patients Showing Treatment Response (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00377637, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2011.

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