Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02550652
Recruitment Status : Active, not recruiting
First Posted : September 15, 2015
Results First Posted : February 26, 2020
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 14, 2015
First Posted Date  ICMJE September 15, 2015
Results First Submitted Date  ICMJE January 14, 2020
Results First Posted Date  ICMJE February 26, 2020
Last Update Posted Date June 30, 2020
Actual Study Start Date  ICMJE November 13, 2015
Actual Primary Completion Date January 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2020)
Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52 [ Time Frame: From baseline to Week 52 ]
Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
Percentage of Participants who Achieve Complete Renal Response (CRR) [ Time Frame: Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2020)
  • Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52 [ Time Frame: From baseline to Week 52 ]
    OR includes both CRR and partial renal response (PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then urine protein:creatinine ratio of <1.0. 2. If baseline protein:creatinine ratio is > 3.0, then urine protein:creatinine ratio of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF.
  • Percentage of Participants With First Protocol Defined Overall Response Over the Course of 52 Weeks [ Time Frame: From baseline to Week 52 (up to approximately 38 months) ]
    OR includes both CRR and partial renal response(PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in upcr, with one of these conditions met: 1. If baseline upcr is ≤3.0, then upcr of <1.0. 2. If baseline pcr is > 3.0, then upcr of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF. Percentage of participants with response at various time points were measured using Kaplan Meier method.
  • Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52 [ Time Frame: From baseline to Week 52 ]
    PRR defined as serum creatinine ≤15% above baseline value, no urinary red cell casts and either RBCs/HPF ≤ 50% above baseline or < 10 RBCs/HPF, 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then a urine protein:creatinine ratio of < 1.0. 2. If baseline protein:creatinine ratio is > 3.0, then a urine protein:creatinine ratio of < 3.0.
  • Percentage of Participants Who Achieve Protocol Defined CRR at Week 24 [ Time Frame: Week 24 ]
    CRR defined as normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
  • Percentage of Participants With First Protocol Defined CRR Over the Course of 52 Weeks [ Time Frame: From Baseline to Week 52 ]
    CRR included normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the ULN range of central laboratory values if baseline serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values. Percentage of participants with response at various time points were measured using Kaplan Meier method.
  • Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52 [ Time Frame: Baseline and Week 52 ]
    Anti-dsDNA antibodies are a group of anti-nuclear antibodies targeting double stranded DNA.
  • Change From Baseline in Complement Component 3 (C3) Levels at Week 52 [ Time Frame: Baseline and Week 52 ]
    Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
  • Change From Baseline in C4 Levels at Week 52 [ Time Frame: Baseline, Week 52 ]
    Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
  • Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52 [ Time Frame: Week 52 ]
    mCRR1 has got two components only, i.e. serum Creatinine and urinary protein to creatinine ratio. mCRR1 is defined by attainment of normalization of serum creatinine as evidenced by 1.) serum creatinine ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine ≤ the ULN range of central laboratory values and 2.) Urinary protein to creatinine ratio <0.5.
  • Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52 [ Time Frame: Week 52 ]
    mCRR2 is defined by normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts), and urinary protein to creatinine ratio <0.5. Normalization of serum creatinine as evidenced by the following: Serum creatinine ≤15% above baseline if baseline (Day 1) serum creatinine is above the normal range of the central laboratory values or ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
  • Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52 [ Time Frame: Week 52 ]
    mCRR3 is defined by normalization of serum creatine as evidenced by serum creatinine ≤ the ULN range of central laboratory values and urinary protein to creatinine ratio < 0.5.
  • Percentage of Participants With Adverse Events [ Time Frame: From Baseline up to Week 52 (up to approximately 38 months) ]
    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
  • Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Infections, Thrombocytopenia and Neutropenia [ Time Frame: From baseline to Week 52 (up to approximately 38 months) ]
    Neutropenia is defined as low neutrophil count (ANC <1.0 x 109/L). Infusion related reaction is defined as a type of hypersensitivity reaction (pruritus, chills, diaphoresis, fever) that develops during or shortly after administration of a drug. Thrombocytopenia is defined as deficiency of platelets (<150 x 10^9/L) in the blood. Infections include all events of infections under the SOC of infections and infestations in this study.
  • Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab [ Time Frame: From baseline to Week 52 (up to approximately 38 months) ]
    Antibodies are a blood protein produced in response to and counteracting a specific antigen.
  • Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels [ Time Frame: Baseline, Week 2, Week 4, Week 12, Week 24, Week 52 ]
    CD19+ B cell is a transmembrane protein that is encoded by the gene CD19.
  • Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab [ Time Frame: Week 0, Week 24, Week 52 ]
  • Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab [ Time Frame: Week 0, Week 24, Week 52 ]
  • Systemic Clearance of Obinutuzumab [ Time Frame: Day 0, Week 24, Week 52 ]
  • Volume of Distribution Under Steady State (Vss) of Obinutuzumab [ Time Frame: Day 0, Week 24, Week 52 ]
  • Terminal Plasma Half-Life (t1/2) of Obinutuzumab [ Time Frame: Day 0, Week 24, Week 52 ]
  • Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score [ Time Frame: Baseline (Day 1), Weeks 4, 12, 24, 36, 52/early termination ]
    Each VAS had a range from 0-100 with higher scores indicating greater symptom impact on global health status.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
  • Percentage of Participants who Achieve a Modified CRR (mCRR1) [ Time Frame: Week 52 ]
  • Perecentage of Participants who Achieve a Second mCRR (mCRR2) [ Time Frame: Week 52 ]
  • Change in Patient's Global Assessment From Baseline to Week 52 [ Time Frame: Baseline to Week 52 ]
  • Peripheral Blood CD19-positive B-cell Count [ Time Frame: Up to approximately 24 months ]
  • Percentage of Participants who Achieve Overall Response [ Time Frame: Week 52 ]
  • Time to First Overall Response Over the Course of 52 weeks [ Time Frame: Baseline (Day 1) to Week 52 ]
  • Percentage of Participants who Achieve Partial Renal Response (PRR) [ Time Frame: Week 52 ]
  • Percentage of Participants who Achieve CRR [ Time Frame: Week 24 ]
  • Time to CRR Over the Course of 52 Weeks [ Time Frame: Baseline (Day 1) to Week 52 ]
  • Percent Change From Baseline in Biomarkers of LN Disease Activity [ Time Frame: Baseline to 104 Week ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis
Brief Summary This Phase II study will compare the efficacy and safety of obinutuzumab plus mycophenolate mofetil (MMF)/mycophenolic acid (MPA) with placebo plus MMF/MPA in participants with proliferative LN.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Lupus Nephritis
Intervention  ICMJE
  • Drug: Mycophenolate Mofetil/Mycophenolic Acid
    MMF/MPA will be administered as per schedule specified in the respective arm.
  • Drug: Obinutuzumab
    Obinutuzumab will be administered as per schedule specified in the respective arm.
    Other Name: Gazyva, GA101, RO5072759
  • Other: Placebo
    Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.
  • Drug: Methylprednisolone
    Methylprednisolone IV will be administered as per schedule specified in the respective arm.
  • Drug: Prednisone
    Prednisone will be administered as per schedule specified in the respective arm.
Study Arms  ICMJE
  • Experimental: Obinutuzumab
    Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
    Interventions:
    • Drug: Mycophenolate Mofetil/Mycophenolic Acid
    • Drug: Obinutuzumab
    • Drug: Methylprednisolone
    • Drug: Prednisone
  • Placebo Comparator: Placebo
    Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
    Interventions:
    • Drug: Mycophenolate Mofetil/Mycophenolic Acid
    • Other: Placebo
    • Drug: Methylprednisolone
    • Drug: Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 12, 2020)
126
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2015)
120
Estimated Study Completion Date  ICMJE June 23, 2020
Actual Primary Completion Date January 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of Systemic Lupus Erythematosus (SLE), according to current American College of Rheumatology (ACR) criteria
  • Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months prior to or during screening. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
  • Proteinuria (urine protein to creatinine ratio) greater than (>) 1.0
  • For women who are not postmenopausal (greater than or equal to [>/=] 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (<) 1 percent (%) per year, during the treatment period and for at least 18 months after the last dose of study drug
  • For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 12 months after the last dose of study drug and agreement to refrain from donating sperm during this same period

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
  • Presence of rapidly progressive glomerulonephritis
  • Severe renal impairment as defined by estimated Glomerular Filtration Rate (GFR) <30 milliliters per minute (mL/min) or the need for dialysis or renal transplant
  • Greater than 50% of glomeruli with sclerosis on renal biopsy
  • Treatment with cyclophosphamide or calcineurin inhibitors within the 3 months prior to randomization
  • Unstable disease with thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions
  • History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
  • Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude participant participation
  • Concomitant chronic conditions, excluding SLE, (e.g., asthma, Crohn's disease) that required oral or systemic steroid use in the 52 weeks prior to screening
  • Previous treatment with an anti-cluster of differentiation (CD20)-targeted therapy within 12 months
  • Previous treatment with a biologic B-cell-targeted therapy (other than anti-CD20) within 6 months of randomization
  • Known intolerance to MMF or MPA
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Colombia,   Costa Rica,   France,   Israel,   Italy,   Mexico,   Panama,   Peru,   Spain,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT02550652
Other Study ID Numbers  ICMJE WA29748
2015-002022-39 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP