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

Lupus Nephritis Clinical Trial

— REGENCY  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04221477
• Other study ID #: CA41705
• Secondary ID: 2019-004034-4220
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 10, 2020
• Est. completion date: February 28, 2029

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 252
• Est. completion date: February 28, 2029
• Est. primary completion date: August 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Nephritis
• 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.
• MMF
MMF willl be administered at a target dose of 2.0 - 2.5 g/day in divided doses through Week 80.
• 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.
• 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.
• Methylprednisolone
Methylprednisolone 80 mg IV will be administered as predmedication prior to infusions.
• Acetaminophen
Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.
• Diphenhydramine
Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Locations

Country	Name	City	State
Argentina	DOM Centro de Reumatología	Ciudad Autónoma de Buenos Aires
Argentina	Sanatorio Allende	Cordoba
Argentina	Organizacion Medica de Investigacion	San Nicolás
Brazil	Instituto Pro-Renal	Curitiba	PR
Brazil	Hospital das Clinicas - FMUSP Ribeirao Preto; Reumatologia	Ribeirao Preto	SP
Brazil	Ser Servicos Especializados Em Reumatologia	Salvador	BA
Brazil	Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*	Sao Bernardo Do Campo	SP
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Colombia	Clinica De La Costa	Barranquilla
Colombia	Hospital Universitario San Ignacio	Bogota
Colombia	Hospital Pablo Tobon Uribe	Medellin
France	HOPITAL HENRI MONDOR; SERVICE DE Nephrologie	Creteil
France	Hopital Claude Huriez; Internal Medicine	Lille
France	Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii	Paris
France	Hopital Bichat Claude Bernard; Nephrologie	Paris
France	Hopital Universitaire; Nephrologie Clinique Medicale B	Strasbourg
France	Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique	Toulouse
Germany	Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie	Berlin
Germany	Städtisches Klinik Dresden-Friedrichstadt; I. Medizinische Klinik	Dresden
Germany	Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III	Dresden
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Universitaetsmedizin Johannes Gutenberg; Rheumatologie	Mainz
Germany	Universitätskrankenhaus Tübingen; Innere Medizin / Hämatologie und Internistische Onkologie	Tübingen
Israel	Meir Medical Center	Kfar- Saba
Israel	Rabin MC- Belinson campus	Petach Tikva
Israel	Chaim Sheba Medical Center; Rheumatology	Ramat-Gan
Israel	Sourasky Medical Centre	Tel-Aviv
Italy	Policlinico di Bari; Divisione di Nefrologia, Dialisi e Trapianto	Bari	Puglia
Italy	A.O. Spedali Civili Di Brescia-P.O. Spedali Civili; Nefrologia	Brescia	Lombardia
Italy	Asst Degli Spedali Civili Di Brescia; Reumatologia Ed Immunologia Clinica	Brescia	Lombardia
Italy	Azienda Ospedaliera Universitaria Careggi	Florence	Toscana
Italy	Ospedale Policlinico San Martino	Genova	Liguria
Italy	ASST Monza - Ospedale San Gerardo; Clinica Nefrologica	Monza	Lombardia
Italy	Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia	Padova	Veneto
Italy	Ospedale ARNAS - P.O."Civico e Benfratelli; UOC Nefrologia e Dialisi	Palermo	Sicilia
Mexico	Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán	Mexico City	Mexico CITY (federal District)
Mexico	Centro de Investigación y Tratamiento Reumatológico S.C.	Mexico, DF	Mexico CITY (federal District)
Mexico	Hospital Universitario; Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo LEON
Peru	Clínica San Juan Bautista CSJB; UNIDAD DE INVESTIGACION EN REUMATOLOGIA E INMUNOLOGIA CSJB	Lima
Peru	Instituto de Ginecología y Reproducción	Lima
Peru	Instituto del Cerebro y la Columna Vertebral SAC	Lima
Peru	Instituto Peruano del Hueso y la Articulación	Lima
Peru	Hospital Nacional Cayetano Heredia; Rheumatology	San Martin de Porres
Poland	SPSK Slaskiego UM w Katowicach; Katedra i Klinika Nefrologii, Endokryn.I Chorob Przemiany Materii	Katowice
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin
Poland	Medyczne Centrum Hetmanska; Rheumatology	Poznan
Poland	Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM; Oddzial Reumat Rehab i Chorob Wewnetrznych	Poznan
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher	Warszawa
Poland	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warszawa
Poland	Szpital Kliniczny Dzieciatka Jezus; Klinika Med. Transplantacyjnej, Nefrologii i Chorob Wew	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Russian Federation	?Kazan (Privolzhsky) Federal University?; Academic Hospital	Kazan	Tatarstan
Russian Federation	Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova	Moscow	Moskovskaja Oblast
Russian Federation	Federal Centre of Heart, Blood and Endocrinology n.a. V.A.Almazov; Rheumatology Department	Saint-Petersburg	Sankt Petersburg
Russian Federation	SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF	Sankt-peterburg	Sankt Petersburg
South Africa	Groote Schuur Hospital and University of Cape Town; E13 Renal Unit & J46 Dept of Medicine	Cape Town
South Africa	Chris Hani Baragwanath Hospital	Johannesburg
South Africa	Panaroma Medical Center; Clinical Trials Department	Panorama
Spain	Hospital Clinic i Provincial; Servicio de Nefrologia	Barcelona
Spain	Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna	Barcelona
Spain	Hospital Ramon y Cajal ; Servicio de Reumatologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Reumatologia	Madrid
United Kingdom	Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital	Cambridge
United States	Univ Colorado Health Sci Ctr	Aurora	Colorado
United States	Wallace Rheumatic Study Center	Beverly Hills	California
United States	University of Alabama at Birmingham Medical Center	Birmingham	Alabama
United States	Georgia Nephrology	Chattanooga	Tennessee
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Kaiser Permanente - Fontana	Fontana	California
United States	North Shore University Hospital	Manhasset	New York
United States	Southwest Rheumatology	Mesquite	Texas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Yale Medical Group; Rheumatology	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	NYU Langone Medical Center; Seligman Center for Advanced Therapeutics	New York	New York
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Stanford University Medical Center	Palo Alto	California
United States	AD-CARE, University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of Utah Health Science center; Internal Medicine for the University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente - San Francisco Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Colombia,  France,  Germany,  Israel,  Italy,  Mexico,  Peru,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

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