ALLEGORY: A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04963296

Collaborator

(none)

200

Enrollment

Locations

Arms

55.6

Anticipated Duration (Months)

2.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of obinutuzumab versus placebo in participants with active, autoantibody-positive systemic lupus erythematosus (SLE) who are treated with standard-of-care therapy.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: Obinutuzumab Drug: Placebo Drug: Acetaminophen/Paracetamol Drug: Diphenhydramine hydrochloride Drug: Methylprednisolone	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy And Safety of Obinutuzumab in Patients With Systemic Lupus Erythematosus

Actual Study Start Date :

Oct 26, 2021

Anticipated Primary Completion Date :

Nov 30, 2025

Anticipated Study Completion Date :

Jun 13, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Obinutuzumab Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.	Drug: Obinutuzumab Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1 and at Weeks 2, 24 and 26. Other Names: Gazyva, GA101, RO5072759 Drug: Acetaminophen/Paracetamol Acetaminophen 650-1000 mg will be administered as premedication prior to infusions. Drug: Diphenhydramine hydrochloride Diphenhydramine 50 mg will be administered as premedication prior to infusions. Drug: Methylprednisolone Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.
Placebo Comparator: Placebo Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.	Drug: Placebo Placebo matching obinutuzumab will be administered by IV on Day 1 and at Weeks 2, 24 and 26. Drug: Acetaminophen/Paracetamol Acetaminophen 650-1000 mg will be administered as premedication prior to infusions. Drug: Diphenhydramine hydrochloride Diphenhydramine 50 mg will be administered as premedication prior to infusions. Drug: Methylprednisolone Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.

Arm

Intervention/Treatment

Experimental: Obinutuzumab

Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1 and at Weeks 2, 24 and 26.

Drug: Obinutuzumab

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1 and at Weeks 2, 24 and 26.

Other Names:

Gazyva, GA101, RO5072759

Drug: Acetaminophen/Paracetamol

Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.

Drug: Diphenhydramine hydrochloride

Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Drug: Methylprednisolone

Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.

Placebo Comparator: Placebo

Placebo participants will receive obinutuzumab matched placebo on Day 1 and at Weeks 2, 24 and 26.

Drug: Placebo

Placebo matching obinutuzumab will be administered by IV on Day 1 and at Weeks 2, 24 and 26.

Drug: Acetaminophen/Paracetamol

Acetaminophen 650-1000 mg will be administered as premedication prior to infusions.

Drug: Diphenhydramine hydrochloride

Diphenhydramine 50 mg will be administered as premedication prior to infusions.

Drug: Methylprednisolone

Methylprednisolone 80 mg IV will be administered as premedication prior to infusions.

Outcome Measures

Primary Outcome Measures

Percentage of Participants who Achieve Systemic Lupus Erythematosus Responder Index (SRI[4]) at Week 52 [Week 52]
SRI(4) requires reduction from baseline of >=4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), no new systems or organs affected, as defined by >=1 new British Isles Lupus Assessment Group (BILAG) A or >=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of >=0.30 points on a 3-point Physician's Global Assessment Visual Analogue Scale (PGA-VAS).

Secondary Outcome Measures

Percentage of Participants who Achieve SRI(6) at Week 52 [Week 52]
SRI(6) requires reduction from baseline of >=6 points in the SLEDAI-2K, no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline using BILAG-2004, and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.
Percentage of Participants who Achieve Sustained Corticosteroid Control [From Week 40 to Week 52]
No treatment with prednisone >=7.5 mg/day (or equivalent) and no receipt of intravenous, intramuscular, or intra-articular corticosteroids.
Time to First BILAG Flare over 52 Weeks [From baseline to Week 52]
Flare is defined as the occurrence of >=1 new BILAG A or >=2 new BILAG B manifestations from the previous visit
Percentage of Participants who Achieve a Sustained SRI(4) Response [From Week 40 to Week 52]
Achievement of SRI(4) at all study visits from Week 40 through Week 52.
Percentage of Participants who Achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) at Week 52 [Week 52]
Reduction of all baseline BILAG-2004 A items to B/C/D and baseline BILAG-2004 B items to C/D; no new systems or organs affected, as defined by >=1 new BILAG A or >=2 new BILAG B items compared with baseline; no net increase in SLEDAI-2K score from baseline; and no worsening from baseline of >=0.30 points on a 3-point PGA-VAS.
Percentage of Participants who Achieve SRI(8) at Week 52 [Week 52]
Percentage of Participants who Achieve SRI(4) at Week 24 [Week 24]
Percentage of Participants who Achieve Clinical SRI(4) at Week 52 [Week 52]
Percentage of Participants who Achieve SRI(4) at Week 52 on Low-dose Corticosteroids [Week 52]
Percentage of Participants who Achieve Lupus Low Disease Activity State (LLDAS) at Week 52 [Week 52]
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale [From baseline to Week 52]
Change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain Domain Scale [From baseline to Week 52]
Change in SF-36 v2 Physical Component Summary Scale [From baseline to Week 52]
Percentage of Participants with Adverse Events [From baseline to approximately 6 years]
Percentage of Participants with Adverse Events of Special Interest (AESIs) [From baseline to approximately 6 years]
Serum Concentration of Obinutuzumab [Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 58, 66, 78, 80, 90, 104 and at early study discontinuation visit]
Percentage of Participants with Anti-drug Antibodies (ADAs) at Baseline [Baseline]
Percentage of Participants with ADAs During the Study [Up to approximately 6 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria >=12 weeks prior to screening
Anti-nuclear antibody (ANA) >=1:80, or anti-dsDNA and/or anti-Sm antibodies above the upper limit of normal (ULN), as determined by the central laboratory at screening
Low C3 and/or low C4 and/or low CH50 complement as determined by the central laboratory at screening
High disease activity at screening, based on; BILAG-2004 (Category A disease in >=1 organ system and/or Category B disease in >=2 organ systems), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (score >=8) and Physician's Global Assessment (PGA) (score >=1.0 on a 0 to 3 visual analogue scale [VAS])
High disease activity on Day 1, based on; SLEDAI-2K (score >=8) and PGA (score >=1.0 on a 0 to 3 VAS)
Current receipt of >=1 of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroid (OCS), antimalarials, conventional immunosuppressants
Other inclusion criteria may apply

Exclusion Criteria:

Pregnancy or breastfeeding
Presence of significant lupus-associated renal disease and/or renal impairment
Receipt of an excluded therapy, including any anti-CD20, anti-CD19 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama; Kirklin Clinic	Birmingham	Alabama	United States	35243
2	Providence Medical Foundation	Fullerton	California	United States	92835
3	University of Colorado Denver, Barbara Davis Center, Center For Clinical Research	Aurora	Colorado	United States	80045
4	Rheumatology Associates of Central Florida	Orlando	Florida	United States	32806
5	Adventhealth Medical Group - Tampa - IM/Rheumatology	Tampa	Florida	United States	33613
6	Arthritis & Rheumatology of Georgia	Atlanta	Georgia	United States	30342
7	Klein & Associates, M.D., P.A.	Hagerstown	Maryland	United States	21740
8	Northwell Health Division of Rheumatology	Great Neck	New York	United States	11021
9	Paramount Medical Research & Consulting, LLC	Middleburg Heights	Ohio	United States	44130
10	Amarillo Center For Clinical Research	Amarillo	Texas	United States	79124
11	Prolato Clinical Research Center	Houston	Texas	United States	77054
12	Organizacion Medica de Investigacion	Buenos Aires		Argentina	C1015ABO
13	DOM Centro de Reumatología	Ciudad Autónoma de Buenos Aires		Argentina	C1111AAJ
14	Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY	San Miguel		Argentina	T4000AXL
15	Ser Servicos Especializados Em Reumatologia	Salvador	BA	Brazil	40150-150
16	Centro Mineiro de Pesquisa - CMIP	Juiz de Fora	MG	Brazil	36010-570
17	Centro de Estudos em Terapias Inovadoras - CETI	Curtiba	PR	Brazil	80030-110
18	Hopital La Cavale Blanche; Rhumatologie	Brest		France	29609
19	CH de Bicêtre; Rhumatologie	Le Kremlin Bicetre		France	94275
20	Ch Pitie Salpetriere; Medecine Interne I	Paris		France	75651
21	HOPITAL COCHIN; Internal Medicine Department	Paris		France	75679
22	Hôpital Sud - CHU de Rennes Service interne	Rennes		France	35033
23	Hopital Hautepierre; Rhumatologie	Strasbourg		France	67098
24	Azienda Ospedaliero-Universitaria Di Ferrara Arcispedale Santanna; Reumatologia	Cona (FE)	Emilia-Romagna	Italy	44124
25	Policlinico Universitario Agostino Gemelli	Roma	Lazio	Italy	00168
26	Asst Degli Spedali Civili Di Brescia; Reumatologia Ed Immunologia Clinica	Brescia	Lombardia	Italy	25125
27	IRCCS S. Raffaele; U.O. Immunologia, Reumatologia, Allergologia e Malattie Rare	Milano	Lombardia	Italy	20132
28	A.O. Universitaria Pisana	Pisa	Toscana	Italy	56126
29	Centro de Investigacion Alberto Bazzoni S.A. de C.V.	Torreon	Coahuila	Mexico	27000
30	Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)	Culiacán Rosales	Sinaloa	Mexico	80000
31	Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel	Mexicali		Mexico	21100
32	Centro de Investigación y Tratamiento Reumatológico S.C.	Mexico, DF		Mexico	11850
33	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey		Mexico	64460
34	Middlemore Hospital; Dept of Rheumatology	Auckland		New Zealand	2025
35	Wellington Hospital	Wellington		New Zealand	6021
36	Hogar Clínica San Juan de Dios	Arequipa		Peru	04000
37	Clínica San Juan Bautista CSJB; UNIDAD DE INVESTIGACION EN REUMATOLOGIA E INMUNOLOGIA CSJB	Lima		Peru	15431
38	Instituto de Ginecología y Reproducción	Lima		Peru
39	Clinica Peruana Americana	Trujillo		Peru	13011
40	Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob	Bydgoszcz		Poland	85-168
41	Prywatna Praktyka Lekarska; Prof.UM dr hab.med Pawel Hryc	Poznan		Poland	61-397
42	Ortopedyczno-Rehabilitacyjny Szpital Kliniczny im. Wiktora Degi UM; Katedra i Klinika Reumatologii	Poznan		Poland	61-545
43	MICS Centrum Medyczne Warszawa	Warszawa		Poland	00-874
44	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warszawa		Poland	02-118
45	REUMATOP Grzegorz Rozumek, Karin Pistorius Spółka Jawna	Wrocław		Poland	52-210
46	State Autonomous Healthcare Institution of Yaroslavl region "Clinical Hospital 9"	Yaroslavl	Jaroslavl	Russian Federation	150042
47	Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova	Moscow	Moskovskaja Oblast	Russian Federation	115522
48	Center of Family Medicine LC	Yekaterinburg	Sankt Petersburg	Russian Federation	620043
49	SBHI of Yaroslavl Region Clinical Hospital #3	Yaroslavl	Volgograd	Russian Federation	150051
50	Scient Res Med Ctr Your Health	Kazan		Russian Federation	420064
51	SBEI of HPI The 1st Moscow State Medical University n.a. I.M. Sechenov of MOH of RF	Moscow		Russian Federation	119021
52	Ryazan State Medical University Named after I.P.Pavlov	Ryazan		Russian Federation	390026
53	FGBU "Federal Medical and Research Center named after V.A.Almazov" Russian Ministry of Health	Sankt-Petersburg		Russian Federation	197341
54	Republican clinical hospital named after G.G. Kuvatov	UFA		Russian Federation	450005
55	Panorama Medical Center; Rheumatology	Cape Town		South Africa	7500
56	TREAD Research	Cape Town		South Africa	7505
57	Winelands Medical Research; Medical Research	Cape Town		South Africa	7600
58	Precise Clinical Solutions (Pty) Ltd	Chatsworth		South Africa	4092
59	Metropolitan Clinical Research Institute	Polokwane		South Africa	0699
60	Greenacres Hospital	Port Elizabeth		South Africa	6045
61	Emmed Research	Pretoria		South Africa	0002
62	Netcare Umhlanga Medical Centre; Rheumatology	Umhlanga		South Africa	4319
63	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Medicina Interna	Santiago de Compostela	LA Coruña	Spain	15706
64	Hospital Meixoeiro	Vigo	Pontevedra	Spain	36214
65	Hospital de Basurto; Servicio de Reumatologia	Bilbao	Vizcaya	Spain	48013
66	Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna	Barcelona		Spain	08035
67	Hospital Clinic i Provincial de Barcelona; Enfermedades Autoinmmunes	Barcelona		Spain	08036
68	Hospital General Universitario Gregorio Marañon; Servicio de Reumatología	Madrid		Spain	28007
69	Addenbrooke'S Hospital; Rheumatology Research Unit	Cambridge		United Kingdom	CB2 2QQ
70	Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine	Leeds		United Kingdom	LS7 4SA
71	Aintree University Hospitals NHS Foundation Trust	Liverpool		United Kingdom	L9 7AL
72	Royal Free Hospital; Department of Rheumatology	London		United Kingdom	NW3 2QG
73	Lancashire Teaching Hospitals NHS Foundation Trust; Lancashire Clinical Research Facility	Preston		United Kingdom	PR2 9HT