BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis (ATLAS)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of BIIB023 in Subjects With Lupus Nephritis

The primary objective of the study is to assess the efficacy of BIIB023 as an add-on treatment to background therapy compared with placebo in combination with background therapy in the treatment of participants with active, biopsy-proven lupus nephritis. The secondary objectives of this study are to assess the safety and tolerability of BIIB023 compared with placebo in this study population.

Study Overview

• Status: Terminated
• Conditions: Lupus Nephritis
• Intervention / Treatment: Biological: Placebo; Biological: BIIB023; Drug: mycophenolate mofetil; Drug: oral corticosteroids

Detailed Description

Participants who complete this study through Week 52 will be offered the option to enter an Extension study under a separate protocol 211LE202 (NCT0193089).

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina
    • Research Site
  • Cordoba, Argentina, 5000
    • Research Site
  • La Plata, Argentina, B1902COS
    • Research Site
  • San Juan, Argentina, 5402DIL
    • Research Site
  • Tucuman, Argentina
    • Research Site
  • Ciudad Autonoma Buenos Aires
    • Capital Federal, Ciudad Autonoma Buenos Aires, Argentina, C1015ABO
      • Research Site
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Research Site
• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Research Site
• Belgium
  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
• Brazil
  • Sao Paulo, Brazil, 04027-000
    • Research Site
  • Mato Grosso
    • Cuiaba, Mato Grosso, Brazil, 78048-902
      • Research Site
• Colombia
  • Barranquilla, Colombia
    • Research Site
  • Bogota, Colombia
    • Research Site
  • Medelin, Colombia
    • Research Site
• France
  • Paris, France, 75651
    • Research Site
  • Paris 9, France, 94010
    • Research Site
  • Gironde
    • Pessac Cedex, Gironde, France, 33604
      • Research Site
  • Nord
    • Lille, Nord, France, 59037
      • Research Site
• Germany
  • Mainz, Germany, 55131
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • Shatin, Hong Kong
    • Research Site
• Hungary
  • Budapest, Hungary, 1097
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
• Italy
  • Pisa, Italy, 56126
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Research Site
  • Gyeonggi-do, Korea, Republic of, 443-721
    • Research Site
• Malaysia
  • Ipoh, Malaysia, 30990
    • Research Site
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Pulau Pinang, Malaysia, 10990
    • Research Site
  • Selangor, Malaysia, 43000
    • Research Site
  • Selangor Darul Ehsan, Malaysia, 41200
    • Research Site
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Research Site
• Mexico
  • Cuauhtemoc, Mexico, 06090
    • Research Site
  • Leon, Mexico, 37000
    • Research Site
  • Mexico City, Mexico, 14000
    • Research Site
  • San Luis Potosi, Mexico, 78240
    • Research Site
  • Coahuila
    • Saltillo, Coahuila, Mexico, 25000
      • Research Site
• Peru
  • Lima, Peru
    • Research Site
• Philippines
  • Manila, Philippines, 1015
    • Research Site
  • Quezon City, Philippines, 1102
    • Research Site
• Poland
  • Lodz, Poland, 92-153
    • Research Site
  • Wroclaw, Poland, 50-417
    • Research Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 123182
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
• Spain
  • Sagunto, Spain, 46520
    • Research Site
• Thailand
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • Research Site
    • Patumwan, Bangkok, Thailand, 10330
      • Research Site
• United States
  • California
    • Torrance, California, United States, 90509
      • Research Site
  • Florida
    • Orlando, Florida, United States, 32806
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States
      • Research Site
  • New York
    • Lake Success, New York, United States, 11020
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7025
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
  • Texas
    • El Paso, Texas, United States, 79905
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Documented diagnosis of systemic lupus erythematosus (SLE) according to current American College of Rheumatology (ACR) criteria. At least 4 ACR criteria must be documented, 1 of which must be a positive antinuclear antibody (ANA), anti Sm, or anti dsDNA antibody.
• Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV lupus nephritis with either active or active/chronic disease, confirmed by biopsy within 3 months prior to Screening. Participants are permitted to have co existing Class V lupus nephritis. If a renal biopsy has not been performed within 3 months of the Screening Visit, one can be performed during the Screening Period after all other eligibility criteria have been confirmed. The local histological diagnosis must be confirmed by the central study pathologist.
• Must have proteinuria at Screening (from a 24 hour urine sample collection) defined as urinary protein:creatinine ratio (uPCR) >1.0 mg/mg.

Key Exclusion Criteria:

• Retinitis, poorly-controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE at Screening
• Estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m^2 (calculated using the abbreviated Modification of Diet in Renal Disease equation) or the presence of oliguria or end-stage renal disease requiring dialysis or transplantation
• Subjects requiring dialysis within 12 months prior to Screening
• History of renal transplant
• Treatment with any biologic B-cell-depleting therapy (e.g., anti-CD20 [rituximab], anti-CD22 [epratuzumab], anti-BLyS/B-cell activating factor [e.g., briobacept, belimumab] therapy), or TACI-Ig within 12 months prior to Run-in Day 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo intravenous (IV) infusion on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48, plus background therapy including oral steroids (prednisone or equivalent) and mycophenolate mofetil (MMF)	Biological: Placebo; Drug: mycophenolate mofetil; titrated to a target daily dose of 2 g (1 g twice daily); Other Names: MMF, Cellcept; Drug: oral corticosteroids; oral corticosteroids (prednisone or equivalent) at a target prednisone dose of 10 mg/day
EXPERIMENTAL: BIIB023 3 mg/kg; BIIB023 3 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	Biological: BIIB023; Drug: mycophenolate mofetil; titrated to a target daily dose of 2 g (1 g twice daily); Other Names: MMF, Cellcept; Drug: oral corticosteroids; oral corticosteroids (prednisone or equivalent) at a target prednisone dose of 10 mg/day
EXPERIMENTAL: BIIB023 20 mg/kg; BIIB023 20 mg/kg IV on Day 1, Week 2, Week 4, Week 8, and every 4 weeks thereafter through Week 48 plus background therapy including oral steroids (prednisone or equivalent) and MMF.	Biological: BIIB023; Drug: mycophenolate mofetil; titrated to a target daily dose of 2 g (1 g twice daily); Other Names: MMF, Cellcept; Drug: oral corticosteroids; oral corticosteroids (prednisone or equivalent) at a target prednisone dose of 10 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve a Complete or Partial Renal Response at Week 52	Complete renal response is defined as: (1) urinary protein:creatinine ratio (uPCR) < 0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline; from a 24 hour urine collection); and (2) estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of < 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR < 3.0 mg/mg if the Day 1 (Baseline) ratio was > 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 [Baseline] or serum creatinine within normal range).	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve Complete Renal Response at Week 52	Complete renal response is defined as uPCR < 0.5 mg/mg with ≥ 50% reduction of uPCR from Baseline (from a 24-hour urine collection) and eGFR within normal range.	Week 52
Duration of Renal Response in Participants Who Achieve Complete Renal Response at Week 52	Duration of response was calculated as the days in between the date of Week 52 visit and the date when the participant last became complete renal responder on or before Week 52 visit. Complete renal response: (1) uPCR <0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range.	Week 52
Time to Renal Response (Partial or Complete) in Participants Who Achieve Renal Response at Week 52	Onset of renal response was calculated as weeks elapsed from baseline date to first visit where renal response was achieved. Complete renal response is defined as: (1) uPCR <0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of < 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR < 3.0 mg/mg if the Day 1 (Baseline) ratio was > 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 [Baseline] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve.	Baseline to Week 52
Percentage of Participants With uPCR > 3.0 mg/mg at Baseline Who Achieve uPCR <1.0 mg/mg at Week 52		Baseline (Day 1), Week 52
Percentage of Participants With Active Urinary Sediment at Baseline Who Have Inactive Urinary Sediment at Week 52	Active urinary sediment is defined by 1 of the following (in the absence of a urinary tract infection or menses): > 5 red blood cell/high power field (RBC/HPF) or above the reference range for the laboratory, and > 5 white blood cell/high power field (WBC/HPF) or above the reference range for the laboratory, and presence of cellular casts (RBC or WBC). Inactive urinary sediment is defined as: < 5 RBC/HPF and < 5 WBC/HPF, or within the laboratory reference range, and no cellular casts (no RBC or WBC casts).	Baseline, Week 52
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Discontinuation During the Run-In Period	AEs that had an onset on or after dosing of MMF on run-in Day 1 up to the first double-blind dose, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above.	Day 1 to Week 12
Number of Participants With AEs, SAEs and AEs Leading to Study Discontinuation During the Double-Blind Period	AEs that had an onset on or after dosing of BIIB023 or placebo, or any pre-existing condition that worsened. AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above.	Week 12 to Week 56
Duration of Renal Response in Participants Who Achieve Partial or Complete Renal Response at Any Time During the Study	Number of days between first visit with response to last consecutive visit with partial or complete response. Complete renal response is defined as: (1) uPCR <0.5 mg/mg with ≥ 50% reduction of uPCR from Day 1 (Baseline) (from a 24 hour urine collection); and (2) eGFR within normal range. Partial renal response is defined as: (1) ≥ 50% reduction in uPCR from Day 1 (Baseline; from a 24-hour urine collection) and, (2) with one of the following: (a) uPCR of < 1.0 mg/mg if the Day 1 (Baseline) was ≤ 3.0 mg/mg, or, (b) uPCR < 3.0 mg/mg if the Day 1 (Baseline) ratio was > 3.0 mg/mg; and stabilization of renal function (eGFR + or - 25% of Day 1 [Baseline] or serum creatinine within normal range). Estimated from the Kaplan-Meier Curve.	up to Week 52

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: November 23, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (ESTIMATE): December 26, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 18, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: 211LE201; 2011-002159-32 (EUDRACT_NUMBER)