A Study to Evaluate Mosunetuzumab in Participants With Systemic Lupus Erythematosus With or Without Active Lupus Nephritis

Official title

A Phase II Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Mosunetuzumab in Patients With Systemic Lupus Erythematosus With or Without Active Lupus Nephritis

Overview

This study will assess how mosunetuzumab works in people who have systemic lupus erythematosus (SLE) who may or may not also have active lupus nephritis (LN).

Interventions

• Drug Mosunetuzumab
  Participants will receive SC mosunetuzumab.

Primary outcome measures

• Proportion of participants who have achieved remission by Week 76 [Time frame: Up to Week 76]

Secondary outcome measures (11)

• Proportion of participants who achieve Definition of Remission in SLE (DORIS) by Week 76 [Time frame: Up to Week 76]
• Proportion of participants who achieve Complete Renal Response (CRR) at Weeks 24, 52, 76, and 104 [Time frame: Weeks 24, 52, 76, and 104]
• Proportion of participants who achieve Partial Renal Response (PRR) at Weeks 24, 52, 76, and 104 [Time frame: Weeks 24, 52, 76, and 104]
• Percentage of participants with adverse events (AEs) [Time frame: Up to 2.5 years]
• Longitudinal change in titers of anti-double-stranded (ds) DNA [Time frame: Up to 2.5 years]
• Longitudinal changes in complement C3 and C4 [Time frame: Up to 2.5 years]
• Serum concentration of mosunetuzumab [Time frame: Up to 2.5 years]
• Percentage of participants with anti-drug antibodies (ADAs) [Time frame: Baseline up to 2.5 years]
• CD19+ absolute counts in blood [Time frame: Up to 2.5 years]
• Change in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue [Time frame: Baseline to Week 76]
• Change in Subject's Global Assessment of Disease Activity (SGA) [Time frame: Baseline to Week 76]

Eligibility criteria

Inclusion criteria

• Diagnosis of SLE for ≥ 6 months as assessed using the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria at screening

Exclusion criteria

• Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
• Treatment with investigational therapy within 30 days or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment and during the study
• Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening, or any planned surgery or procedure requiring hospitalization during the 12 weeks following study drug administration
• Alcohol or substance abuse within the 12 months prior to screening
• Active infection of any kind, excluding fungal infection of the nail beds
• Any major episode of infection as defined by the protocol
• History of serious recurrent or chronic infection
• History of progressive multifocal leukoencephalopathy (PML)
• Tuberculosis (TB) infection
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years
• Active overlap syndrome with mixed connective tissue disease or systemic sclerosis within the 12 months prior to screening or during screening
• Catastrophic or severe antiphospholipid syndrome within the 12 months prior to screening or during screening. Antiphospholipid syndrome adequately controlled by anticoagulant therapy for at least 2 months prior to screening is acceptable
• High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions
• Active severe or unstable lupus-associated neuropsychiatric disease or where, in the opinion of the investigator, it is likely to require treatment with protocol-disallowed therapies. Examples of neuropsychiatric SLE manifestations include, but are not limited to the following: meningitis, retinitis, cerebral vasculitis, myelopathy, demyelination syndromes, acute confusional state, psychosis, acute stroke or stroke syndrome, cranial neuropathy, status epilepticus or seizures, cerebellar ataxia, and mononeuritis multiplex
• History of any non-SLE disease treated with oral, intravenous, or intramuscular corticosteroids for more than 14 days in total during the one year prior to Day 1
• History of treatment with any T cell-engaging bispecific antibodies or CAR-T therapy within the past 2 years
• Receipt of any live or attenuated vaccine in the 28 days prior to or during screening

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 7 centers

• Clnica SER da Bahia — Salvador
• L2IP ?Instituto de Pesquisas Clínicas Ltda. — Brasília
• IPC MT Instituto de Pesquisas Clinicas do Mato Grosso — Cuiab
• Complexo Hospitalar de Niteroi — Niterói
• LMK Servios Mdicos S/S Ltda — Porto Alegre
• Hospital das Clinicas de Ribeirao Preto — Ribeiro Preto
• Hospital das Clnicas da Faculdade de Medicina da USP — São Paulo

Colombia · 3 centers

• Clinica de la Costa S.A.S — Barranquilla
• Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM — Bogotá
• Hospital Pablo Tobon Uribe — Medellín

South Africa · 3 centers

• Emmed Research — Pretoria
• University of Cape Town Kidney and Hypertension Research Unit — Cape Town
• Clinical Trials Network Helderberg — Somerset West

Italy · 2 centers

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civ — Brescia

Mexico · 2 centers

• Centro Medico del Angel — Mexicali
• Centro de Investigación y Tratamiento Reumatológico S.C. — México

Publications

• Martins E, Chindalore VL, Sheng XR, Schroeder AV, Chen V, Mody H, Arjomandi A, Mao HA, Hassan I, Dankiewicz-Fares I, Agachi S, Omachi TA, Garg JP, Pendergraft WF 3rd. Phase Ib, multicentre, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of subcutaneously administered mosunetuzumab in participants with systemic lupus erythematosus. Lupu PMID 42309556

Identifiers

NCT: NCT07598396 · GA45799 · 2024-519930-22-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗