BIIB023 Proof-of-Concept Study in Participants With Lupus Nephritis - Full Text View

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:

Drug Information available for: Mycophenolic acid Mycophenolate sodium Mycophenolate mofetil hydrochloride Mycophenolate mofetil

Genetic and Rare Diseases Information Center resources: Lupus Nephritis Glomerulonephritis

U.S. FDA Resources

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

Show 81 Study Locations

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	Mycophenolic Acid Mycophenolate mofetil Antibiotics, Antineoplastic Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 29, 2016

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