A First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7507062 in Participants With Systemic Lupus Erythematosus

Roche

Status and phase: Enrolling; Phase 1

Conditions: Systemic Lupus Erythematosus

Treatments: Drug: RO7507062; Drug: Tocilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05835986

BP44315

2022-502632-39-00 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RO7507062 in participants with systemic lupus erythematosus (SLE). The study will have 2 parts: Part 1 is a single ascending dose-finding (SAD) part and Part 2 is a dose escalation with fractionated dosing part.

Full description

Tocilizumab is an additional investigational medicinal product (IMP), which may be used at the investigator's discretion when required in case of clinical presentation of cytokine release syndrome (CRS).

Enrollment: 70 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have a diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) Classification Criteria at least 24 weeks prior to Screening and should have been treated for SLE according to standard clinical practice.
• Presence of anti-double stranded DNA (dsDNA), anti-Smith (Sm), anti-ribonucleoprotein (RNP) or anti-Sjögren's syndrome antigen A (SS-A) above the upper limit of normal (ULN); or, positive anti-nuclear antibody (ANA; ≥ 1:160).
• Active SLE disease, as demonstrated by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score of ≥4 with at least 1 positive clinical item.
• For participants receiving oral corticosteroids (OCS), treatment with ≤ 20 milligram per day (mg/day) prednisone or equivalent, during Screening, at a dose that has been stable for at least 7 days prior to Day 1.
• For participants receiving conventional immunosuppressants (e.g., azathioprine, sulfasalazine, mycophenolate mofetil [≤ 3.0 grams per day], mycophenolic acid [≤ 3 grams per day], methotrexate [oral, SC, or intramuscular routes]), and calcineurin inhibitors [oral]), treatment should be at a stable dose for at least 6 weeks prior to Screening and during Screening and expected to remain stable during the study.

Exclusion criteria

• Active or unstable lupus-associated neuropsychiatric disease.
• Catastrophic or severe antiphospholipid syndrome within 12 months prior to Screening or during Screening.
• Presence of severe lupus-associated renal disease that is likely to require treatment with cyclophosphamide, B-cell-depleting therapies, other biologic or targeted therapies.
• Organ-threatening SLE manifestations (e.g., active myocarditis) considered to be severe by the Investigator.
• Severe active systemic autoimmune disease other than SLE.
• Active infection of any kind, excluding fungal infection of the nail beds.
• History of serious recurrent or chronic infection, especially; recurring, chronic infections specifically related to respiratory issues.
• Moderate or severe chronic obstructive pulmonary disease (COPD).
• History of progressive multifocal leukoencephalopathy (PML).
• History of macrophage-activation syndrome and/or hemophagocytic lymphohistiocytosis.
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the 5 years prior to the Screening visit (with the exception of basal cell carcinoma, non melanoma skin cancer, and cervical cancer in situ, if these have been adequately treated and are considered cured).
• Intolerance or contraindication to study therapies including history of severe allergic or anaphylactic reactions to monoclonal antibodies (mAbs) or known hypersensitivity to any component of the RO7507062 injection.
• History of infection with hepatitis B virus (HBV), or positive serology indicative of current or past HBV infection.
• Human immunodeficiency virus (HIV; positive HIV antibody test) and active hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA]).
• Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection.
• Receipt of any anti- cluster of differentiation (CD)19 or anti-CD20 therapy such as blinatumomab, obinutuzumab, rituximab, ocrelizumab, or ofatumumab less than 6 months prior to screening or during screening.
• Receipt of Inhibitors of Janus kinase (JAK), Bruton tyrosine kinase, or tyrosine kinase 2 including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, and fenebrutinib,or any investigational agent within 30 days prior to screening or during screening.
• Receipt of Cyclophosphamide or a biologic therapy such as, but not limited to, adalimumab, etanercept, golimumab, infliximab, belimumab,ustekinumab, anifrolumab, secukinumab, or atacicept, within 4 weeks prior to enrollment.
• Active tuberculosis or history of recurring or severe active tuberculosis, or a positive Interferon Gamma Release Assay (IGRA). Latent tuberculosis which has been treated prior to baseline is not exclusive.
• Receipt of an investigational therapy (except severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] vaccines) within 30 days or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment and during the study.
• Immunoglobulin (IgG) level of <6 gram per liter (g/L).
• Estimated glomerular filtration rate (eGFR) <45 milliliter per minute (mL/min)/1.73-meter square (m^2).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Part 1: SAD: RO7507062

Experimental group

Description:

Participants will receive RO7507062 at an assigned dose as subcutaneous (SC) injection on Day 1.

Treatment:

Drug: Tocilizumab

Drug: RO7507062

Part 2: Dose Escalation with Fractionated Dosing: RO7507062

Experimental group

Description:

Participants will receive RO7507062 as SC injection at the dose determined in Part 1, on Day 1 and as escalated doses on subsequent days.

Treatment:

Drug: Tocilizumab

Drug: RO7507062