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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: RO7507062; Drug: Tocilizumab

Detailed Description

Tocilizumab is an additional investigational medicinal product (IMP), which will be used when required in case of clinical presentation of cytokine release syndrome (CRS). Data on the efficacy of tocilizumab in ameliorating the symptoms of CRS related to RO7507062 will be collected in this study.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BP44315 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité Research Organisation GmbH
• Netherlands
  • Leiden, Netherlands, 2333
    • Active, not recruiting
    • Centre For Human Drug Research; Research
• Poland
  • Pozna?, Poland, 61-848
    • Recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu; Osrodek Badan Klinicznych Wczesnych Faz
  • Warszawa, Poland, 04-141
    • Recruiting
    • Wojskowy Instytut Medyczny- Panstwowy Instytut Badawczy; Centrum Wsparcia Badan Klinicznych
  • Warszawa, Poland, 02-739
    • Recruiting
    • MICS Centrum Medyczne Damiana, Walbrzyska
• South Africa
  • Bloemfontein, South Africa, 9301
    • Recruiting
    • FARMOVS (Pty) Ltd; University of the Free State, Pharmacology Building
• Spain
  • Cordoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofia; Servicio de Reumatologia
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon; Servicio de Reumatología
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre; Servicio de Reumatologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 must 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.
• 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.
• For transitioning participants, stable hormonal therapy 3-6 months prior to screening.

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 protocol-prohibited 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 past 5 years (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).

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: Part 1: SAD: RO7507062; Participants will receive RO7507062 at an assigned dose as subcutaneous (SC) injection on Day 1.	Drug: RO7507062; RO7507062 solution for injection will be administered SC as specified in each treatment arm.; Drug: Tocilizumab; Tocilizumab solution for infusion will be administered intravenously at 8 milligram per kilogram (mg/kg) for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.; Other Names: Actemra, RoActemra
Experimental: 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 at an escalated dose, based on emergent safety data, on Day 8.	Drug: RO7507062; RO7507062 solution for injection will be administered SC as specified in each treatment arm.; Drug: Tocilizumab; Tocilizumab solution for infusion will be administered intravenously at 8 milligram per kilogram (mg/kg) for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.; Other Names: Actemra, RoActemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Number of Participants with DLAEs		Day 8 through Day 36
Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)		Day 1 through Day 29
Number of Participants with Adverse Events (AEs) and CRS	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.	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Concentration of RO7507062	Up to approximately 12 months
Time to Maximum Serum Concentration (Tmax) of RO7507062	Up to approximately 12 months
Maximum Serum Concentration (Cmax) 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 Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUClast) 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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2023
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: April 19, 2023
• First Posted (Actual): April 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 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: BP44315; 2022-502632-39-00 (Other Identifier: EU Trial Number)

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