search
Back to results

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

Primary Purpose

Systemic Lupus Erythematosus

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
RO7507062
Tocilizumab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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 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 a 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. 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. History of active or latent tuberculosis or a positive Interferon Gamma Release Assay (IGRA). 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).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Part 1: SAD: RO7507062

    Part 2: Dose Escalation with Fractionated Dosing: RO7507062

    Arm Description

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

    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.

    Outcomes

    Primary Outcome Measures

    Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)
    Part 2: Number of Participants with DLAEs
    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.

    Secondary Outcome Measures

    Serum Concentration of RO7507062
    Time to Maximum Serum Concentration (Tmax) of RO7507062
    Maximum Serum Concentration (Cmax) of RO7507062
    Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7507062
    Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUClast) of RO7507062
    Apparent Terminal Half-Life (T1/2) of RO7507062
    Terminal Rate Constant (λz) of RO7507062
    Apparent Volume of Distribution (Vz/F) of RO7507062
    Apparent Total Body Clearance (CL/F) of RO7507062
    Number of Participants with Anti-Drug Antibodies (ADAs) to RO7507062

    Full Information

    First Posted
    April 19, 2023
    Last Updated
    October 6, 2023
    Sponsor
    Hoffmann-La Roche
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05835986
    Brief Title
    A First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7507062 in Participants With Systemic Lupus Erythematosus
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 31, 2023 (Anticipated)
    Primary Completion Date
    November 30, 2027 (Anticipated)
    Study Completion Date
    November 30, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hoffmann-La Roche

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Systemic Lupus Erythematosus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    70 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Part 1: SAD: RO7507062
    Arm Type
    Experimental
    Arm Description
    Participants will receive RO7507062 at an assigned dose as subcutaneous (SC) injection on Day 1.
    Arm Title
    Part 2: Dose Escalation with Fractionated Dosing: RO7507062
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    RO7507062
    Intervention Description
    RO7507062 solution for injection will be administered SC as specified in each treatment arm.
    Intervention Type
    Drug
    Intervention Name(s)
    Tocilizumab
    Other Intervention Name(s)
    Actemra, RoActemra
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Part 1: Number of Participants with Dose Limiting Adverse Events (DLAEs)
    Time Frame
    Day 1 through Day 28
    Title
    Part 2: Number of Participants with DLAEs
    Time Frame
    Day 8 through Day 36
    Title
    Number of Participants with Adverse Events (AEs) and CRS
    Description
    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.
    Time Frame
    Up to approximately 14 months
    Secondary Outcome Measure Information:
    Title
    Serum Concentration of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Time to Maximum Serum Concentration (Tmax) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Maximum Serum Concentration (Cmax) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUClast) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Apparent Terminal Half-Life (T1/2) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Terminal Rate Constant (λz) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Apparent Volume of Distribution (Vz/F) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Apparent Total Body Clearance (CL/F) of RO7507062
    Time Frame
    Up to approximately 12 months
    Title
    Number of Participants with Anti-Drug Antibodies (ADAs) to RO7507062
    Time Frame
    Up to approximately 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    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 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 a 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. 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. History of active or latent tuberculosis or a positive Interferon Gamma Release Assay (IGRA). 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).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    BP44315 https://forpatients.roche.com/
    Phone
    888-662-6728 (U.S. Only)
    Email
    global-roche-genentech-trials@gene.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Trials
    Organizational Affiliation
    Hoffmann-La Roche
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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).

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs