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

This study has been terminated.
(Results from a pre-specified criteria did not demonstrate sufficient efficacy to warrant continuation of the study.)
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01499355
First received: November 23, 2011
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
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. Participants who complete this study through Week 52 will be offered the option to enter an Extension study under a separate protocol 211LE202 (NCT0193089).

Condition Intervention Phase
Lupus Nephritis
Biological: BIIB023
Biological: Placebo
Drug: Mycophenolate Mofetil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of BIIB023 in Subjects With Lupus Nephritis

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Percentage of participants who achieve a complete or partial renal response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Complete renal response is defined as urinary protein:creatinine ratio (uPCR) <0.5 mg/mg with ≥50% reduction of uPCR from Baseline (from a 24-hour urine collection) and estimated glomerular filtration rate (eGFR) within normal range. Partial renal response is defined as ≥50% reduction in uPCR from Baseline with one of the following: a) uPCR of <1.0 mg/mg if the Baseline was ≤ 3.0 mg/mg, or b) uPCR <3.0 mg/mg if the Baseline ratio was >3.0 mg/mg; and stabilization of renal function (eGFR ± 25% of Baseline or serum creatinine within normal range).


Secondary Outcome Measures:
  • Percentage of participants who achieve complete renal response at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Complete renal response is defined as urinary protein:creatinine ratio (uPCR) <0.5 mg/mg with ≥ 50% reduction of uPCR from Baseline (from a 24-hour urine collection) and estimated glomerular filtration rate (eGFR) within normal range.

  • Duration of response in participants who achieve complete renal response at week 52 [ Time Frame: Up to Week 64 ] [ Designated as safety issue: No ]
  • Percentage of participants uPCR >3.0 mg/mg at Baseline who achieve uPCR <1.0 mg/mg [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
  • Time to renal response (partial or complete) in participants who achieve renal response [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Percentage of participants with active urinary sediment at Baseline who have inactive urinary sediment at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    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 • Presence of cellular casts (RBC or WBC) Inactive urinary sediment defined as: • < 5 RBC/HPF and < 5 WBC/HPF, or within the laboratory reference range, and • no cellular casts (no RBC or WBC casts)

  • Number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to study discontinuation [ Time Frame: Up to Week 56 ] [ Designated as safety issue: Yes ]
  • Duration of renal response [ Time Frame: Up to week 64 ] [ Designated as safety issue: No ]

Enrollment: 188
Study Start Date: July 2012
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + Background Therapy
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
Intravenous (IV) Infusion
Drug: Mycophenolate Mofetil
Mycophenolate mofetil titrated to a target daily dose of 2 g (1 g twice daily)
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 Mycophenolate Mofetil (MMF)
Biological: BIIB023
Intravenous (IV) Infusion of BIIB023
Drug: Mycophenolate Mofetil
Mycophenolate mofetil titrated to a target daily dose of 2 g (1 g twice daily)
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 Mycophenolate Mofetil (MMF)
Biological: BIIB023
Intravenous (IV) Infusion of BIIB023
Drug: Mycophenolate Mofetil
Mycophenolate mofetil titrated to a target daily dose of 2 g (1 g twice daily)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Subjects 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 (GFR) <30 mL/min per 1.73 m^2 (calculated using the abbreviated Modification of Diet in Renal Disease [MDRD] equation) or the presence of oliguria or end-stage renal disease [ESRD] 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/BAFF [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.

  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: NCT01499355

  Hide Study Locations
Locations
United States, California
Research Site
La Jolla, California, United States, 92037-0943
Research Site
Torrance, California, United States, 90509
United States, Florida
Research Site
Orlando, Florida, United States, 32806
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02118
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 55905
United States, Missouri
Research site
St. Louis, Missouri, United States, 63110
United States, New York
Research Site
Lake Success, New York, United States, 11042
United States, North Carolina
Research Site
Chapel Hill, North Carolina, United States, 27599-7025
Research Site
Raleigh, North Carolina, United States, 27617
United States, Ohio
Research Site
Columbus, Ohio, United States, 43210
United States, Tennessee
Research Site
Memphis, Tennessee, United States, 38119
United States, Texas
Research Site
El Paso, Texas, United States, 79905
Research Site
Houston, Texas, United States, 77030
Argentina
Research Site
Capital Federal, Ciudad Autonoma Buenos Aires, Argentina, C1015ABO
Research Site
San Miguel de Tucuman, Tucuman, Argentina, 4000
Research Site
San Miguel de Tucuman, Tucuman, Argentina, T4000AXL
Research Site
Cipolletti, Argentina, R8324EMD
Research Site
Ciudad Autonoma Buenos Aires, Argentina, 1181
Research Site
Ciudad Autonoma Buenos Aires, Argentina, 1419
Research Site
Cordoba, Argentina, 5000
Research Site
Cordoba, Argentina, C5016
Research Site
La Plata, Argentina, B1902COS
Research Site
San Juan, Argentina, 5402DIL
Research Site
Santa Fe, Argentina, S3000EPV
Australia, Victoria
Research Site
Parkville, Victoria, Australia, 3052
Belgium
Research Site
Leuven, Belgium, 3000
Research Site
Liege, Belgium, 4000
Brazil
Research Site
Cuiaba, Mato Grosso, Brazil, 78048-902
Research Site
Porto Alegre, Rio Grande do Sul, Brazil, 90020-090
Research Site
Sao Paulo, Brazil, 04027-000
Colombia
Research Site
Barranquilla, Colombia
Research Site
Bogota, Colombia
Research Site
Medelin, Colombia
France
Research Site
Pessac Cedex, Gironde, France, 33604
Research Site
Lillie, Nord, France, 59037
Research Site
Paris 9, France, 94010
Research Site
Paris, France, 75651
Germany
Research Site
Aachen, Germany, 52074
Research Site
Mainz, Germany, 55131
Research Site
Muenchen, Germany, 80336
Hong Kong
Research Site
Hong Kong, Hong Kong
Research Site
N.t., Hong Kong
Hungary
Research Site
Budapest, Hungary, 1023
Research Site
Budapest, Hungary, 1097
Research Site
Debrecen, Hungary, 4032
Italy
Research Site
Padova, Italy, 35128
Research Site
Pisa, Italy, 56126
Korea, Republic of
Research Site
Busan, Korea, Republic of, 602-715
Research Site
Gwangju, Korea, Republic of, 501-757
Research Site
Gyeonggi-do, Korea, Republic of, 443-721
Malaysia
Research Site
Kuantan, Pahang, Malaysia, 25100
Research Site
Kuching, Sarawak, Malaysia, 93586
Research Site
Ipoh, Malaysia, 30990
Research Site
Kuala Lumpur, Malaysia, 59100
Research Site
Pulau Pinang, Malaysia, 10990
Research Site
Selangor Darul Ehsan, Malaysia, 41200
Research Site
Selangor, Malaysia, 43000
Mexico
Research Site
Saltillo, Coahuila, Mexico, 25000
Research Site
Mexico, Distrito Federal, Mexico, 14000
Research Site
Cuauhtemoc, Mexico, 06090
Research Site
Leon, Mexico, 37000
Research Site
Merida, Mexico, 97130
Research Site
San Luis Potosi, Mexico, 78240
Peru
Research Site
Lima, Peru, LIMA 01
Research Site
Lima, Peru, Lima 11
Research Site
Lima, Peru, Lima 21
Research Site
Lima, Peru, Lima 27
Research Site
Lima, Peru, Lima 29
Research Site
Lima, Peru, Lima 41
Philippines
Research Site
Manila, Philippines, 1015
Research Site
Quezon City, Philippines, 1102
Poland
Research Site
Lodz, Poland, 92-153
Research Site
Wroclaw, Poland, 50-417
Portugal
Research Site
Coimbra, Portugal, 3000-075
Russian Federation
Research Site
Moscow, Russian Federation, 123182
Research Site
Saint Petersburg, Russian Federation, 197022
Serbia
Research Site
Belgrade, Serbia, 11000
Spain
Research Site
Sagunto, Spain, 46520
Research Site
Zaragoza, Spain, 50009
Thailand
Research Site
Bangkoknoi, Bangkok, Thailand, 10700
Research Site
Patumwan, Bangkok, Thailand, 10330
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01499355     History of Changes
Other Study ID Numbers: 211LE201  2011-002159-32 
Study First Received: November 23, 2011
Last Updated: July 28, 2016
Health Authority: Israel: Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Malaysia: National Pharmaceutical Control Bureau
Australia: Department of Health and Ageing Therapeutic Goods Administration
Hong Kong: Department of Health
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Serbia: Medicines and Medical Devices Agency of Serbia
Thailand: Ministry of Public Health
Spain: Spanish Agency of Medicines
Mexico: Federal Commission for Sanitary Risks Protection
Portugal: National Pharmacy and Medicines Institute
Colombia: National Institutes of Health
South Africa: Medicines Control Council
Malaysia: Ministry of Health
Thailand: Food and Drug Administration
Peru: Instituto Nacional de Salud
Hungary: National Institute of Pharmacy
Canada: Health Canada
Philippines: Bureau of Food and Drugs
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration
Portugal: National Authority of Medicines and Health Products, IP (INFARMED)
Turkey: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Germany: Paul-Ehrlich-Institut
Russia: Ministry of Health of the Russian Federation
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolate mofetil
Mycophenolic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2016