An Open-label, Multicenter, Dose Escalation, First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered RO7507062 in Participants With Systemic Lupus Erythematosus
Overview
- Phase
- Phase 1
- Intervention
- RO7507062
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 70
- Locations
- 42
- Primary Endpoint
- Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)
- Status
- Recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
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.
Detailed 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).
Investigators
Eligibility Criteria
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
- •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.
Arms & Interventions
Part 1: SAD: RO7507062
Participants will receive RO7507062 at an assigned dose as subcutaneous (SC) injection on Day 1.
Intervention: RO7507062
Part 1: SAD: RO7507062
Participants will receive RO7507062 at an assigned dose as subcutaneous (SC) injection on Day 1.
Intervention: Tocilizumab
Part 2: Dose Escalation with Fractionated Dosing: RO7507062
Participants will receive RO7507062 as SC injection at the dose determined in Part 1, on Day 1 and as escalated doses on subsequent days.
Intervention: RO7507062
Part 2: Dose Escalation with Fractionated Dosing: RO7507062
Participants will receive RO7507062 as SC injection at the dose determined in Part 1, on Day 1 and as escalated doses on subsequent days.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)
Time Frame: Day 1 through Day 29
Part 2: Fractionated Dose Cohort: Number of Participants with DLAEs
Time Frame: Day 1 through to the end of the 28-day safety evaluation period
Number of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 12 months
Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and CRS, will be graded based on the American Society for Transplantation and Cell Therapy (ASTCT) criteria.
Secondary Outcomes
- Time to Maximum Serum Concentration (Tmax) of RO7507062(Up to approximately 12 months)
- Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7507062(Up to approximately 12 months)
- Area Under the Serum Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration (AUClast) of RO7507062(Up to approximately 12 months)
- Serum Concentration of RO7507062(Up to approximately 12 months)
- Maximum Serum Concentration (Cmax) of RO7507062(Up to approximately 12 months)
- Apparent Terminal Half-Life (T1/2) of RO7507062(Up to approximately 12 months)
- Terminal Rate Constant (λz) of RO7507062(Up to approximately 12 months)
- Apparent Volume of Distribution (Vz/F) of RO7507062(Up to approximately 12 months)
- Apparent Total Body Clearance (CL/F) of RO7507062(Up to approximately 12 months)
- Number of Participants with Anti-Drug Antibodies (ADAs) to RO7507062(Up to approximately 12 months)