A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered Mosunetuzumab to Participants With Systemic Lupus Erythematosus

A Phase Ib, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered Mosunetuzumab to Participants With Systemic Lupus Erythematosus

This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of mosunetuzumab in participants with systemic lupus erythematosus (SLE).

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Mosunetuzumab; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GA43191 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• Georgia
  • Tbilisi, Georgia, 0112
    • Active, not recruiting
    • LLC Arensia Exploratory Medicine
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Completed
    • ICS ARENSIA Exploratory Medicine
• Poland
  • Bydgoszcz, Poland, 85-168
    • Recruiting
    • Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
  • Poznan, Poland, 61-545
    • Recruiting
    • Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM; Oddzial Reumat Rehab i Chorob Wewnetrznych
• Ukraine
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 01135
      • Withdrawn
      • Medical Center of Limited Liability Company ?Harmoniya krasy?
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Recruiting
      • Pinnacle Research Group; Llc, Central
  • New York
    • Syracuse, New York, United States, 13210
      • Recruiting
      • SUNY Upstate Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria at least 12 weeks or more prior to screening
• Presence of one or more of the following SLE autoantibodies documented within the 12 months prior to screening or during screening: positive ANA (greater than or equal to 1:160); anti dsDNA above the upper limit of normal (ULN); anti-Sm above the ULN
• Active SLE disease, as demonstrated by a SLEDAI-2K total score of greater than or equal to 4 at screening
• Current receipt of one or more of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroids (OCSs), antimalarial agents, conventional immunosuppressants
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol
• For men on mycophenolate mofetil (MMF): With a female partner of childbearing potential, men who are not surgically sterile must remain abstinent (refrain from heterosexual intercourse) or use contraception as defined by the protocol

Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab and 3 months after the final dose of tocilizumab
• Active severe or unstable lupus-associated neuropsychiatric disease that is likely to require treatment with protocol-prohibited therapies
• Active overlap syndrome with mixed connective tissue disease or systemic sclerosis within 12 months prior to screening or during screening
• Catastrophic or severe antiphospholipid syndrome within 12 months prior to screening or during screening
• Presence of significant lupus-associated renal disease and/or renal impairment that is likely to require treatment with protocol-prohibited therapies
• Peripheral CD19+ B-cell count < 25 cells/uL
• Receipt of an investigational therapy within 30 days or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment and during the study
• Receipt of any of the following excluded therapies: any anti-CD19 or anti-CD20 therapy such as blinatumomab, obinutuzumab, rituxumab, ocrelizumab, or ofatumumab less than 12 months prior to screening or during screening; inhibitors of JAK, Bruton tyrosine kinase, or tyrosine kinase 2, including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib, or any investigational agent within 30 days prior to screening or during screening; tacrolimus, ciclosporin, or voclosporin within 30 day prior to screening or during screening; cyclophosphamide or a biologic therapy such as but not limited to belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during 2 months prior to screening or during screening; any live or attenuated vaccine during 28 days prior to screening or during screening
• High risk for any clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions
• Significant or uncontrolled medical disease that would preclude participation
• HIV infection, acute or chronic hepatitis B virus (HBV), acute or chronic hepatitis C (HCV) infection, tuberculosis (TB) infection, known or suspected chronic active Epstein-Barr virus (EBV) infection, or cytomegalovirus (CMV) infection
• Active infection of any kind, excluding fungal infection of the nail beds
• Any major episode of infection that fulfills any of the following criteria: requires hospitalization during 8 weeks prior to screening or during screening; requires treatment with IV antibiotics (or anti-infective medications) during 8 weeks prior to screening or during screening; requires treatment with oral antibiotics (or anti-infective medications) during 2 weeks prior to screening or during screening
• History of serious recurrent or chronic infection
• History of progressive multifocal leukoencephalopathy (PML)
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years
• Major surgery requiring hospitalization during 4 weeks prior to screening or during screening or any planned surgery or procedure requiring hospitalization during 12 weeks following study drug administration
• Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening
• Intolerance or contraindication to study therapies including history of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of mosunetuzumab injection
• Positive serum human chorionic gonadotropin measures at screening
• Any of the following laboratory parameters: aspartate transaminase (AST) or alanine transaminase (ALT) > 2.5 x upper limit of normal (ULN); total bilirubin > 1.5 x ULN; absolute neutrophil count (ANC) < 2.0 x 10^9/L (< 2000/mm^3); platelet count < 100 x 10^9/L (100,000 mm^3); hemoglobin < 100 g/L (10 g/dL); estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m^2 calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation; positive serum human chorionic gonadotropin measured at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-fractionated/Dose-finding; Participants will receive a single dose of mosunetuzumab.	Drug: Mosunetuzumab; Participants will receive subcutaneous (SC) mosunetuzumab on either Day 1 or on Days 1 and 8.; Drug: Tocilizumab; Participants will receive intravenous (IV) tocilizumab as needed to manage adverse reactions.
Experimental: Fractionated/Dose-escalation; Participants will receive a fractionated (divided) dose of mosunetuzumab on Days 1 and 8.	Drug: Mosunetuzumab; Participants will receive subcutaneous (SC) mosunetuzumab on either Day 1 or on Days 1 and 8.; Drug: Tocilizumab; Participants will receive intravenous (IV) tocilizumab as needed to manage adverse reactions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with adverse events (AEs)	For a minimum of 12 months after mosunetuzumab dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum concentration of mosunetuzumab	Through Month 12
Peripheral B-cell count	Through Month 12, then every 6 months thereafter
Duration of B-cell depletion	Through Month 12, then every 6 months thereafter
Change from baseline in anti-drug antibodies (ADAs)	Through Month 12

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Estimated): September 25, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: December 10, 2021
• First Submitted That Met QC Criteria: December 10, 2021
• First Posted (Actual): December 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: GA43191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No