A Study to understand the Effectiveness, Safety, and what the body does to Mosunetuzumab in participants with Systemic Lupus Erythematosus with or without Active Lupus Nephritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune System Phenomena [G13], Diseases [C] - Immune System Diseases [C20]

Trial duration

18 May 2026 → ongoing

Decision date (initial)

2025-09-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Others, Pharmacodynamic

To evaluate the efficacy of mosunetuzumab in conferring drug-free remission

Secondary objectives 9

1. To evaluate the efficacy of mosunetuzumab in conferring clinical response (also known as DORIS)
2. To evaluate the efficacy of mosunetuzumab in conferring complete renal response (CRR) (Cohort 1 only)
3. To evaluate the efficacy of mosunetuzumab in conferring partial renal response (PRR) (Cohort 1 only)
4. To evaluate the safety of mosunetuzumab
5. To evaluate the effect of mosunetuzumab on lupus disease activity biomarkers
6. To characterize Pharmacokinetic (PK) of mosunetuzumab
7. To evaluate the immunogenicity of mosunetuzumab
8. To evaluate the pharmacodynamics effects of mosunetuzumab on circulating B cells
9. To evaluate the efficacy of mosunetuzumab on patient reported outcome measures

Conditions and MedDRA coding

Systemic Lupus Erythematosus (SLE) With or Without Active Lupus Nephritis (LN)

Regulatory references

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. Cohort 1 Active Class III and/or Class IV LN per 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) Criteria as confirmed through local laboratory testing of a kidney biopsy sample obtained within 3 months of screening, which must meet all of the following criteria: – ≥3 points on the NIH activity index, excluding any contribution from interstitial activity – < 50% glomerulosclerosis and < 50% tubulointerstitial fibrosis – Concomitant Class V disease is permitted
3. Cohort 1 Participants with biopsy-proven active LN as described above must also meet the following criteria for enrollment: – urinary protein-to-creatinine ratio (UPCR) ≥ 1.5 g/g on a 24-hour urine collection at screening per the central laboratory – C3 complement below the lower limit of normal at screening per the central laboratory – Active LN despite treatment for at least 6 months with standard nonsteroidal LN therapy (e.g. mycophenolate mofetil (MMF), cyclophosphamide, azathioprine, voclosporin, other calcineurin inhibitors, belimumab, rituximab) – Participants previously treated with B-cell-depleting therapy (e.g. rituximab) are eligible to participate as long as the last treatment was given more than 6 months prior to screening
4. Cohort 2 Participants with SLE must have autoantibody positivity, hypocomplementemia, and high disease activity at screening despite treatment with advanced therapy
5. Cohort 2 Active disease despite treatment for at least 6 months with either cyclophosphamide or a biologic (e.g., belimumab, anifrolumab, rituximab or other anti-CD20 agent) – Participants previously treated with B cell-depleting therapy (e.g. rituximab) are eligible to participate as long as the last treatment was given more than 6 months prior to screening
6. Cohort 2 Participants with SLE must have autoantibody positivity, hypocomplementemia, and high disease activity at screening despite treatment with advanced therapy as follows: - Either an anti-double-stranded DNA antibody or anti-Smith antibody above the upper limit of normal at screening per the central laboratory - C3 complement level below the lower limit of normal at screening per the central laboratory - Active disease at screening, defined as total SLEDAI-2K >= 12, as well as extrarenal SLEDAI-2K score >= 8

Exclusion criteria 6

1. Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required. Participants of childbearing potential must have a negative blood pregnancy test result at screening prior to initiation of study treatment
2. 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
3. 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
4. Alcohol or substance abuse within the 12 months prior to screening
5. Active infection of any kind, excluding fungal infection of the nail beds
6. History of progressive multifocal leukoencephalopathy (PML)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achievement of drug-free remission by Week 76

Secondary endpoints 14

1. Proportion of participants who achieve DORIS remission by Week 76
2. Proportion of participants who achieve CRR at Weeks 24, 52, 76, and 104
3. Proportion of participants who achieve PRR at Weeks 24, 52, 76, and 104
4. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) and Cytokine-Release Syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity determined according to the 2019 American Society for Transplantation and Cellular Therapy (ASTCT) CRS and ICANS Consensus grading criteria.
5. Change from baseline in targeted vital signs
6. Change from baseline in targeted clinical laboratory test results
7. Longitudinal changes in titers of anti-dsDNA and anti-Smith antibodies
8. Longitudinal changes in complement C3 and C4
9. Serum concentrations of mosunetuzumab at specified timepoints
10. Relevant PK parameters of mosunetuzumab
11. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
12. B cell levels in the blood (CD19+, absolute counts in blood) at specified timepoints
13. Change in Functional Assessment of Chronic Illness Therapy (FACIT) – Fatigue from baseline to Week 76
14. Change in Subject’s Global Assessment of Disease Activity (SGA) from baseline to Week 76

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications