A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis (REGENCY)

• ClinicalTrials.gov Identifier: NCT04221477
• Recruitment Status: Active, not recruiting
• First Posted: January 9, 2020
• Last Update Posted: September 26, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 7, 2020
• First Posted Date: January 9, 2020
• Last Update Posted Date: September 26, 2023
• Actual Study Start Date: August 10, 2020
• Estimated Primary Completion Date: August 16, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 20, 2021): Percentage of Participants with Complete Renal Response (CRR) [ Time Frame: At Week 76 ]
• Original Primary Outcome Measures (submitted: January 7, 2020): Percentage of Participants with Complete Renal Response (CRR) [ Time Frame: From baseline to Week 76 ]

Current Secondary Outcome Measures (submitted: April 11, 2023)

• Percentage of Participants who Achieve a Proteinuric Response [ Time Frame: At Week 76 ]
• Percentage of Participants who Achieve Complete Renal Response (CRR) with Successful Prednisone Taper at Week 76 [ Time Frame: At Week 76 ]
• Percentage of Participants who Achieve an Overall Renal Response (ORR), Defined as Achievement of Either CRR or Partial Renal Response (PRR) [ Time Frame: At Week 50 ]
• Percentage of Participants who Experience Death or Renal-related Events [ Time Frame: From baseline to Week 76 ]
• Mean Change in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: From baseline to Week 76 ]
• Change in Anti-dsDNA Titer [ Time Frame: From baseline to Week 50 ]
• Change in Complement C3 [ Time Frame: From baseline to Week 50 ]
• Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [ Time Frame: From baseline to Week 76 ]
• Time to Onset of CRR [ Time Frame: From baseline to Week 76 ]
• Change in Fatigue (FACIT-F) Scale [ Time Frame: From baseline to Week 76 ]
• Percentage of Participants who Achieve CRR with Serum Creatinine Criteria [ Time Frame: At Week 76 ]
• Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: From baseline to Week 76 ]
• Percentage of Participants with Adverse Events of Special Interest (Infusion Related Reactions, Neutropenia, Infections, Thrombocytopenia) [ Time Frame: From baseline to Week 76 ]
• Maximum Serum Concentration of Obinutuzumab [ Time Frame: Baseline, Week 2, 4, 12, 26, 36, 50, 52, 64, 76 and early study discontinuation ]
• Percentage of Participants with Anti-Drug Antibodies (ADAs) at Baseline and ADAs Post-Treatment [ Time Frame: From baseline to Week 76 ]
• Change from Baseline in Total Peripheral B-Cell Count [ Time Frame: Baseline, Week 4, 12, 24, 50 and 76 ]

Original Secondary Outcome Measures (submitted: January 7, 2020)

• Percentage of Participants Who Achieved CRR with Estimated Glomerular Filtration Rate (eGFR) criterion [ Time Frame: From baseline to Week 76 ]
• Percentage of Participants with Overall Renal Response (ORR), Defined as Achievement of Either Complete Renal Response (CRR) or Partial Renal Response (PRR) [ Time Frame: From baseline to Week 52 ]
• Change in Anti-dsDNA Titer [ Time Frame: From baseline to Week 52 ]
• Change in Complement C3 [ Time Frame: From baseline to Week 52 ]
• Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [ Time Frame: From baseline to Week 76 ]
• Change in eGFR [ Time Frame: From baseline to Week 76 ]
• Time to Onset of CRR [ Time Frame: From baseline to Week 76 ]
• Change in Fatigue (FACIT-F) Scale [ Time Frame: From baseline to Week 76 ]
• Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: From baseline to Week 76 ]
• Percentage of Participants with Adverse Events of Special Interest (Infusion Related Reactions, Neutropenia, Infections, Thrombocytopenia) [ Time Frame: From baseline to Week 76 ]
• Maximum Serum Concentration of Obinutuzumab [ Time Frame: Baseline, Week 2, 4, 12, 26, 36, 52, 64, 76 and early study discontinuation ]
• Percentage of Participants with Anti-Drug Antibodies (ADAs) at Baseline and ADAs Post-Treatment [ Time Frame: From baseline to Week 76 ]
• Change from Baseline in Total Peripheral B-Cell Count [ Time Frame: Baseline, Week 4, 12, 24, 56 and 76 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis (REGENCY)
• Brief Summary: This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Lupus Nephritis

Intervention

• Drug: Obinutuzumab
  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.
  Other Name: Gazyva, GA101, RO5072759
• Drug: MMF
  MMF willl be administered at a target dose of 2.0 - 2.5 g/day in divided doses through Week 80.
• Drug: Prednisone
  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.
• Drug: Placebo
  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.
• Drug: Methylprednisolone
  Methylprednisolone 80 mg IV will be administered as predmedication prior to infusions.
• Drug: Acetaminophen
  Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.
• Drug: Diphenhydramine
  Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Study Arms

• Experimental: Obinutuzumab

  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.

  Interventions:

  • Drug: Obinutuzumab
  • Drug: MMF
  • Drug: Prednisone
  • Drug: Methylprednisolone
  • Drug: Acetaminophen
  • Drug: Diphenhydramine
• Placebo Comparator: Placebo

  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.

  Interventions:

  • Drug: Obinutuzumab
  • Drug: MMF
  • Drug: Prednisone
  • Drug: Placebo
  • Drug: Methylprednisolone
  • Drug: Acetaminophen
  • Drug: Diphenhydramine

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 20, 2021): 252
• Original Estimated Enrollment (submitted: January 7, 2020): 250
• Estimated Study Completion Date: February 28, 2029
• Estimated Primary Completion Date: August 16, 2024 (Final data collection date for primary outcome measure)

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 patient participation
• Known active infection of any kind or recent major episode of infection
• Intolerance or contraindication to study therapies
• Other exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Colombia, France, Germany, Israel, Italy, Mexico, Peru, Poland, Russian Federation, South Africa, Spain, United Kingdom, United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT04221477
• Other Study ID Numbers: CA41705; 2019-004034-42 ( EudraCT Number ); 2023-503628-22-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: September 2023