TriangleNCT04221477 · CITED IN SOURCE DOCUMENTS
A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With ISN/RPS 2003 Class III or IV Lupus Nephritis
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-07-21
This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in participants with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With Complete Renal Response (CRR)
Percentage of Participants Who Achieve CRR With Successful Prednisone Taper at Week 76
Percentage of Participants Who Achieve a Proteinuric Response
Mean Change in eGFR
Percentage of Participants Who Experience Death or Renal-related Events
Percentage of Participants Who Achieve an Overall Renal Response (ORR)
Change From Baseline in Fatigue Assessed Using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale
Change in Log-transformed Anti-double-stranded Deoxyribonucleic Acid (Anti-dsDNA) Titer
Change in Complement C3
Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Time to Onset of CRR
Percentage of Participants Who Achieve CRR With Serum Creatinine Criteria
Number of Participants With Adverse Events (AEs)
Number of Participants With Adverse Events of Special Interest (AESIs)
Number of Participants With Anti-Drug Antibodies (ADAs) Positive Post-Treatment
Total Peripheral B-Cell (CD19) Count
Concentration of Obinutuzumab in Serum
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Key Inclusion Criteria: * Diagnosis of active or active/chronic ISN/RPS 2003 Class III or IV proliferative LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease * Urine protein to creatinine ratio greater than or equal to (\>/=) 1 on a 24-hour collection * Other inclusion criteria may apply Key Exclusion Criteria: * Pregnancy or breastfeeding * Severe renal impairment or the need for dialysis or renal transplantation * Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening * Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude participant participation * Known active infection of any kind or recent major episode of infection * Intolerance or contraindication to study therapies * Other exclusion criteria may apply
- healthy Volunteers
- false
- maximum Age
- 75 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
- intervention Names
- Drug: Obinutuzumab
- Drug: MMF
- Drug: Prednisone
- Drug: Methylprednisolone
- Drug: Acetaminophen
- Drug: Diphenhydramine
- label
- Obinutuzumab
- type
- EXPERIMENTAL
- description
- Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. After study unblinding, participants may be eligible for further open-label obinutuzumab treatment.
- intervention Names
- Drug: Obinutuzumab
- Drug: MMF
- Drug: Prednisone
- Drug: Placebo
- Drug: Methylprednisolone
- Drug: Acetaminophen
- Drug: Diphenhydramine
- label
- Placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Obinutuzumab
- Placebo
- description
- Obinutuzumab will be administered by IV infusion at a dose of 1000 mg at Baseline and Weeks 2, 24, 26, 50 (group 2: placebo), and 52 and subsequently from Week 80 and every 6 months thereafter, based on response.
- name
- Obinutuzumab
- other Names
- Gazyva, GA101, RO5072759
- type
- DRUG
- arm Group Labels
- Obinutuzumab
- Placebo
- description
- MMF willl be administered at a target dose of 2.0 - 2.5 g/day in divided doses through Week 80.
- name
- MMF
- type
- DRUG
- arm Group Labels
- Obinutuzumab
- Placebo
- description
- Prednisone 0.5 mg/kg/day (maximum 60 mg/day) will be started on Day 2. Beginning on Day 15, prednisone will be tapered to 5 mg/day and continued until Week 80.
- name
- Prednisone
- type
- DRUG
- arm Group Labels
- Placebo
- description
- Placebo matching obinutuzumab will be administered by IV infusion at baseline and Weeks 0, 2, 24, 26, 50 and 52 and subsequently from Week 80 and every 6 months thereafter based on response.
- name
- Placebo
- type
- DRUG
- arm Group Labels
- Obinutuzumab
- Placebo
- description
- Methylprednisolone 80 mg IV will be administered as predmedication prior to infusions.
- name
- Methylprednisolone
- type
- DRUG
- arm Group Labels
- Obinutuzumab
- Placebo
- description
- Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.
- name
- Acetaminophen
- type
- DRUG
- arm Group Labels
- Obinutuzumab
- Placebo
- description
- Diphenhydramine 50 mg will be administered as premedication prior to infusions.
- name
- Diphenhydramine
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 271
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- CRR was defined as an achievement of all the following criteria: urinary protein-to-creatinine ratio (UPCR) \<0.5 gram/gram (g/g); estimated glomerular filtration rate (eGFR) \>=85% of baseline, as calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Obinutuzumab and placebo were compared using Cochran-Mantel-Haenszel (CMH) test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using fully conditional specification (FCS) predicted mean matching method. Percentage have been rounded off.
- measure
- Percentage of Participants With Complete Renal Response (CRR)
- time Frame
- At Week 76
- secondary Outcomes
- description
- CRR with successful prednisone was defined as the achievement of CRR at Week 76 with no receipt of prednisone \>7.5 milligrams per day (mg/day) (or equivalent) from Week 64 through Week 76. CRR was defined as achievement of all the following criteria: UPCR \<0.5 g/g; eGFR \>=85% of baseline, as calculated using the CKD-EPI equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentage have been rounded off.
- measure
- Percentage of Participants Who Achieve CRR With Successful Prednisone Taper at Week 76
- time Frame
- At Week 76
- description
- Proteinuric response was defined as an achievement of all the following criteria: UPCR \<0.8 g/g and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentage have been rounded off.
- measure
- Percentage of Participants Who Achieve a Proteinuric Response
- time Frame
- At Week 76
- description
- Change in eGFR from baseline to Week 76 was analyzed using Analysis of Covariance (ANCOVA) model with covariates baseline eGFR and the stratification factors race and region. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with 0. Missing data was imputed by multiple imputations using FCS predicted mean matching method. mL/min/1.73 m\^2 = milliliters per minute per 1.73 square meters. Adjusted mean has been reported.
- measure
- Mean Change in eGFR
- time Frame
- At Week 76
- description
- Percentage of participants with death or renal-related events were defined as participants with one or more of the following events: Death; Treatment failure; Worsening proteinuria, defined as a confirmed ≥50% increase in UPCR to a value ≥3 g/g; Worsening eGFR, defined as a confirmed ≥30% decrease in eGFR to a value \<60. Early study withdrawal due to lack of efficacy was an intercurrent event. Participants experiencing the intercurrent event were considered as participants with events under composite strategy. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentages have been rounded off.
- measure
- Percentage of Participants Who Experience Death or Renal-related Events
- time Frame
- From Day 1 to Week 76
- description
- ORR was defined as achievement of either CRR or PRR. CRR was defined as achievement of all of the criteria: UPCR \<0.5 g/g; eGFR ≥85% of baseline, as calculated using the CKD-EPI equation. PRR was defined as achievement of all of the following criteria: ≥50% reduction in UPCR from baseline; UPCR \<1 g/g (or \<3 g/g if the baseline UPCR was ≥3 g/g); eGFR ≥85% of baseline, as calculated using the CKD-EPI equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Percentage have been rounded off.
- measure
- Percentage of Participants Who Achieve an Overall Renal Response (ORR)
- time Frame
- At Week 50
- description
- The FACIT-F is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The sum of all responses resulted in the FACIT-F score of 0 (worse score) to 52 (better score). Higher scores indicate less fatigue. Change in FACIT-F score from baseline at Week 76 was analyzed using ANCOVA model with covariates baseline FACIT-F score and the stratification factors race and region. Death was considered as an intercurrent event which was handled under composite strategy by imputing FACIT-F score after death with 0. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Adjusted mean has been reported.
- measure
- Change From Baseline in Fatigue Assessed Using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale
- time Frame
- At Week 76
- description
- Anti-dsDNA are types of autoantibodies produced by the immune system and are indicators of lupus. Anti-dsDNA data was log-transformed before analysis. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Analysis was performed using ANCOVA. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with upper limit of quantification (ULOQ, 890 international units/milliliter \[IU/mL\]). Adjusted mean has been reported.
- measure
- Change in Log-transformed Anti-double-stranded Deoxyribonucleic Acid (Anti-dsDNA) Titer
- time Frame
- At Week 50
- description
- C3 is a marker of inflammation. Analysis was performed using ANCOVA. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with lower limit of quantification (LLOQ)/2 under composite strategy. LLOQ at the central lab was set for C3 at 0.100 grams/liters (g/L). Missing data was imputed by multiple imputations using FCS predicted mean matching method. Adjusted mean has been reported.
- measure
- Change in Complement C3
- time Frame
- At Week 50
- description
- The SLEDAI-2K is a 24-item instrument that evaluates clinical symptoms and laboratory markers across nine organ systems and was used to capture changes in lupus-related disease activity. SLE manifestations are assessed by the clinician if present within the last 30 days and added to determine the total SLEDAI-2K score, which ranges from 0 to 105. Higher scores indicate increased disease activity. The analysis was performed using ANCOVA. Death was considered as an intercurrent event which was handled under composite strategy by imputing data after death with 105, the highest possible score. Missing data was imputed by multiple imputations using FCS predicted mean matching method. Adjusted mean has been reported.
- measure
- Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
- time Frame
- At Week 76
- description
- CRR was defined as an achievement of all the following criteria: UPCR \<0.5 g/g; eGFR \>=85% of baseline, as calculated using the CKD-EPI equation and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Participants who experienced the intercurrent events before achieving CRR as well as participants who completed 76-week treatment period without experiencing CRR were censored at Week 76. Summary statistics of time to onset of CRR are Kaplan-Meier estimates. A log-rank test was used to compare obinutuzumab and placebo. The median time to onset of CRR was greater than Week 76 due to considering the upper limit of the Week 76 analysis visit window in this analysis. The upper limit of the Week 76 visit window was 3 days prior to the next obinutuzumab or placebo infusion or 30 days beyond Week 76 whichever is shorter.
- measure
- Time to Onset of CRR
- time Frame
- From baseline (Day 1) up to 80.3 weeks
- description
- CRR with serum creatinine criteria was defined as achievement of all the following criteria: UPCR \<0.5 g/g; Serum creatinine ≤ ULN, as determined by the central laboratory; serum creatinine not increased from baseline by \> 25% and no occurrence of intercurrent events of rescue therapy, treatment failure, death or early study withdrawal. Analysis was performed using CMH test adjusting for the stratification factors region and race. Percentage have been rounded off.
- measure
- Percentage of Participants Who Achieve CRR With Serum Creatinine Criteria
- time Frame
- At Week 76
- description
- An AE was 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 AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
- measure
- Number of Participants With Adverse Events (AEs)
- time Frame
- Up to Week 76
Full study description
- brief Summary
- This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in participants with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.
Source references
- references
- citation
- Furie RA, Rovin BH, Garg JP, Santiago MB, Aroca-Martinez G, Zuta Santillan AE, Alvarez D, Navarro Sandoval C, Lila AM, Tumlin JA, Saxena A, Irazoque Palazuelos F, Raghu H, Yoo B, Hassan I, Martins E, Sehgal H, Kirchner P, Ross Terres J, Omachi TA, Schindler T, Pendergraft WF 3rd, Malvar A; REGENCY Trial Investigators. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. N Engl J Med. 2025 Apr 17;392(15):1471-1483. doi: 10.1056/NEJMoa2410965. Epub 2025 Feb 7.
- pmid
- 39927615
- type
- DERIVED
- citation
- Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.
- pmid
- 37528520
- type
- DERIVED
- citation
- Dossier C, Hogan J. Response to Majeranowski. Pediatr Nephrol. 2021 Jun;36(6):1653. doi: 10.1007/s00467-021-04982-4. Epub 2021 Mar 10. No abstract available.
- pmid
- 33693991
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- ival in Patients with Previously Untreated FL Figure 5 14.3 Active Lupus Nephritis Study Design and Population The efficacy of GAZYVA was evaluated in REGENCY (NCT04221477), a Phase III, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in 271 patients with ISN/RPS 2003 Class III or IV, with or witho
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- in patients with ISN/RPS 2003 Class III or IV with or without concomitant Class V lupus nephritis in the REGENCY and NOBILITY studies, up to week 76. REGENCY (NCT04221477) is a Phase III study which included 136 patients treated with GAZYVA plus standard therapy consisting of mycophenolate mofetil (MMF) and corticosteroids [ see
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Preserved source evidence · Not medical advice