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A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous RO7121932 in Participants With Multiple Sclerosis.

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RO7121932
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening Participants with RMS or PMS who fulfil international panel criteria for diagnosis (McDonald 2017 criteria) Participants not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up) Female participants must practice abstinence or otherwise use contraception Exclusion Criteria: Evidence of recent clinical disease activity Evidence of recent MRI activity Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML Known presence of other neurological disorders that may mimic MS including but not limited to: neuromyelitis optica spectrum disease, Lyme disease, untreated Vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, and untreated hypothyroidism Known active or uncontrolled bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds, including participants exhibiting symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6 weeks prior to Day 1 Participants with a current diagnosis of epilepsy Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening. Basal or squamous cell carcinoma of the skin that has been excised and is considered cured and in situ carcinoma of the cervix treated with apparent success by curative therapy >1 year prior to screening is not exclusionary Any concomitant disease that may require treatment with systemic corticosteroids or immunosuppressants during course of the study History of currently active primary or secondary (non-drug-related) immunodeficiency History of hypersensitivity to biologic agents or any of the excipients in the formulation Cohorts 5 and 6 and later cohorts, as appropriate: Participants with a history of spinal cord compression, raised intra-cerebral pressure, clinically significant vertebral joint pathology or any other current abnormalities in the lumbar region which could prevent the lumbar puncture procedure. Prior/Concomitant Therapy: Treatment with any approved MS treatment at Screening. Participants may become eligible after completion of a washout period prior to acquiring any screening laboratory tests but should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial Previous treatment with alemtuzumab, cladribine, mitoxantrone, cyclophosphamide, total body irradiation, bone marrow transplantation, and hematopoietic stem cell transplantation. For the USA only, previous treatment with daclizumab Previous treatment with anti-CD20 B-cell-depleting therapies (e.g., rituximab, ocrelizumab, or ofatumumab) <12 months prior to acquiring any screening laboratory tests, ≥12 months prior to acquiring any screening laboratory tests, if B-cells are outside the normal range, or not back to individual baseline ± 20% (if data are available), if discontinuation of a prior B-cell depletion therapy was motivated by safety reasons Current or prior treatment with natalizumab (if <24 months prior to acquiring any screening laboratory tests) Prior/Concurrent Clinical Study Experience: - Participation in an investigational drug medicinal product or medical device study within 30 days before Screening or within five times the PD or PK half-life (if known), whichever is longer Diagnostic Assessments: Positive result on human immunodeficiency virus (HIV1) and HIV2, hepatitis C, or hepatitis B Participants with suicidal ideation or behavior within 6 months prior to Screening or participants who, in the Investigator's judgment, pose a suicidal or homicidal risk Vaccination with a live or live-attenuated vaccine within 6 weeks prior to Day 1

Sites / Locations

  • Stanford University Medical Center; Stanford Neuroscience Health CenterRecruiting
  • Yale University Multiple Sclerosis Center
  • University of South FloridaRecruiting
  • University of Massachusetts Medical School
  • UC Health, LLC.Recruiting
  • UZ GentRecruiting
  • Montreal Neurological Institute and Hospital; Pharmacy DepartmentRecruiting
  • Universitätsklinikum "Carl Gustav Carus"; MS Center DresdenRecruiting
  • Universitätsmedizin Göttingen Georg-August-Universität; Klinik für NeurologieRecruiting
  • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-ZentrumRecruiting
  • Universitätsklinikum Münster Klinik u. Poliklinik f. NeurologieRecruiting
  • Hadassah University Hospital - Ein KeremRecruiting
  • Tel Aviv Sourasky Medical Center; Department of Neurology
  • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi MultiplaRecruiting
  • Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie NeuromuscolariRecruiting
  • ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical HospitalRecruiting
  • Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych FazRecruiting
  • Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial NeurologicznyRecruiting
  • MedPoloniaRecruiting
  • Osrodek Badan Klinicznych Euromedis
  • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
  • SPSK nr 1; Klinika NeurologiiRecruiting
  • Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
  • ARENSIA Exploratory Medicine, County Emergency HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RO7121932: Dose Escalation Cohorts 1 to 6

Arm Description

Participants will receive a single IV dose of RO7121932 on treatment Day 1. The planned starting dose of RO7121932 is 7 milligrams (mg) and will be escalated up to 2000 mg. The maximum dose will not exceed 4000 mg. Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) with Severity of AEs Measured According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v 5)
Percentage of Participants With Abnormal Laboratory Findings
Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters
Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an interview-based instrument used to assess baseline incidence of suicidal ideation and behavior. The assessment includes "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation (if present), from 0 to 5. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior, with 5 being the most severe.

Secondary Outcome Measures

Time to Maximum Observed Concentration (Tmax) of RO7121932
Maximum Observed Serum Concentration (Cmax) of RO7121932
Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose
Area Under the Serum Concentration-Time Curve up to the Last Measurable Concentration (AUClast)
AUC From Time 0 to Infinity (AUCinf)
Total Body Clearance (CL) Of RO7121932
Terminal Rate Constant of RO7121932
Apparent Terminal Half-Life (T1/2) of RO7121932
Cerebrospinal Fluid (CSF) Concentration of RO7121932 (Cohorts 5 and 6, and later cohorts, as appropriate)
Percentage of Participants With Anti-RO7121932 Antibodies
Time Course of B cells in Blood and CSF
Change From Baseline in B-cell count in Blood and CSF

Full Information

First Posted
January 4, 2023
Last Updated
October 11, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05704361
Brief Title
A Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous RO7121932 in Participants With Multiple Sclerosis.
Official Title
A Multiple-center, Non-randomized, Open-label, Adaptive, Single Ascending Dose, Phase I Study to Investigate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of RO7121932 Following Intravenous Administration in Patients With Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 11, 2021 (Actual)
Primary Completion Date
January 31, 2025 (Anticipated)
Study Completion Date
January 31, 2025 (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 primary purpose of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) doses of RO7121932 in participants with multiple sclerosis (MS)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RO7121932: Dose Escalation Cohorts 1 to 6
Arm Type
Experimental
Arm Description
Participants will receive a single IV dose of RO7121932 on treatment Day 1. The planned starting dose of RO7121932 is 7 milligrams (mg) and will be escalated up to 2000 mg. The maximum dose will not exceed 4000 mg. Doses may be repeated, adjusted downwards, or intermediate doses may be investigated based on emerging data.
Intervention Type
Drug
Intervention Name(s)
RO7121932
Intervention Description
Participants will receive a single dose of RO7121932 administered as IV infusion.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) with Severity of AEs Measured According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v 5)
Time Frame
Day 1 to Day 169
Title
Percentage of Participants With Abnormal Laboratory Findings
Time Frame
Day 1 to Day 169
Title
Percentage of Participants With Abnormal Vital Signs and Electrocardiogram (ECG) Parameters
Time Frame
Day 1 to Day 169
Title
Change From Baseline in Suicide Risk as Assessed Using the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
The C-SSRS is an interview-based instrument used to assess baseline incidence of suicidal ideation and behavior. The assessment includes "yes" or "no" responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings are provided for severity of ideation (if present), from 0 to 5. A score of 0 is assigned if no suicide risk is present. A score of 1 or higher indicates suicidal ideation or behavior, with 5 being the most severe.
Time Frame
Day 1 to Day 169
Secondary Outcome Measure Information:
Title
Time to Maximum Observed Concentration (Tmax) of RO7121932
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Maximum Observed Serum Concentration (Cmax) of RO7121932
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours (h) (AUC0-168h) Postdose
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Area Under the Serum Concentration-Time Curve up to the Last Measurable Concentration (AUClast)
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
AUC From Time 0 to Infinity (AUCinf)
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Total Body Clearance (CL) Of RO7121932
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Terminal Rate Constant of RO7121932
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Apparent Terminal Half-Life (T1/2) of RO7121932
Time Frame
Predose and post dose at 0.5 hour, 1 hour (or end of infusion), 2 hour, 3 hour (or end of infusion), 8 hour on Day 1, and on Days 2, 3, 5, 8, 15, 22, 29, 57, 85, 113, 169
Title
Cerebrospinal Fluid (CSF) Concentration of RO7121932 (Cohorts 5 and 6, and later cohorts, as appropriate)
Time Frame
Day 1 to Day 169
Title
Percentage of Participants With Anti-RO7121932 Antibodies
Time Frame
Predose on Day 1, and on Days 8, 22, 29, 57, 85, 169
Title
Time Course of B cells in Blood and CSF
Time Frame
Day 1 to Day 169
Title
Change From Baseline in B-cell count in Blood and CSF
Time Frame
Day 1 to Day 169

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Expanded Disability Status Scale (EDSS) score ≤7.0 at Screening Participants with RMS or PMS who fulfil international panel criteria for diagnosis (McDonald 2017 criteria) Participants not treated with any approved MS treatment at Screening and not planning to start on any MS therapy during the study (including follow-up) Female participants must practice abstinence or otherwise use contraception Exclusion Criteria: Evidence of recent clinical disease activity Evidence of recent MRI activity Participants who have active progressive multifocal leukoencephalopathy (PML), have had confirmed PML, or have a high degree of suspicion for PML Known presence of other neurological disorders that may mimic MS including but not limited to: neuromyelitis optica spectrum disease, Lyme disease, untreated Vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, and untreated hypothyroidism Known active or uncontrolled bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds, including participants exhibiting symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 6 weeks prior to Day 1 Participants with a current diagnosis of epilepsy Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, allergic, renal, or other major diseases History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening. Basal or squamous cell carcinoma of the skin that has been excised and is considered cured and in situ carcinoma of the cervix treated with apparent success by curative therapy >1 year prior to screening is not exclusionary Any concomitant disease that may require treatment with systemic corticosteroids or immunosuppressants during course of the study History of currently active primary or secondary (non-drug-related) immunodeficiency History of hypersensitivity to biologic agents or any of the excipients in the formulation Cohorts 5 and 6 and later cohorts, as appropriate: Participants with a history of spinal cord compression, raised intra-cerebral pressure, clinically significant vertebral joint pathology or any other current abnormalities in the lumbar region which could prevent the lumbar puncture procedure. Prior/Concomitant Therapy: Treatment with any approved MS treatment at Screening. Participants may become eligible after completion of a washout period prior to acquiring any screening laboratory tests but should not be withdrawn from therapies for the sole purpose of meeting eligibility for the trial Previous treatment with alemtuzumab, cladribine, mitoxantrone, cyclophosphamide, total body irradiation, bone marrow transplantation, and hematopoietic stem cell transplantation. For the USA only, previous treatment with daclizumab Previous treatment with anti-CD20 B-cell-depleting therapies (e.g., rituximab, ocrelizumab, or ofatumumab) <12 months prior to acquiring any screening laboratory tests, ≥12 months prior to acquiring any screening laboratory tests, if B-cells are outside the normal range, or not back to individual baseline ± 20% (if data are available), if discontinuation of a prior B-cell depletion therapy was motivated by safety reasons Current or prior treatment with natalizumab (if <24 months prior to acquiring any screening laboratory tests) Prior/Concurrent Clinical Study Experience: - Participation in an investigational drug medicinal product or medical device study within 30 days before Screening or within five times the PD or PK half-life (if known), whichever is longer Diagnostic Assessments: Positive result on human immunodeficiency virus (HIV1) and HIV2, hepatitis C, or hepatitis B Participants with suicidal ideation or behavior within 6 months prior to Screening or participants who, in the Investigator's judgment, pose a suicidal or homicidal risk Vaccination with a live or live-attenuated vaccine within 6 weeks prior to Day 1
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: BP42230 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
Facility Information:
Facility Name
Stanford University Medical Center; Stanford Neuroscience Health Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Name
Yale University Multiple Sclerosis Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06473
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UC Health, LLC.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Montreal Neurological Institute and Hospital; Pharmacy Department
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 2B4
Country
Canada
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Neurologie
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Recruiting
Facility Name
Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
City
München
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Münster Klinik u. Poliklinik f. Neurologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Name
Hadassah University Hospital - Ein Kerem
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Individual Site Status
Recruiting
Facility Name
Tel Aviv Sourasky Medical Center; Department of Neurology
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Individual Site Status
Withdrawn
Facility Name
IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Name
ARENSIA Exploratory Medicine Phase I, PMSI Republican Clinical Hospital
City
Chisinau
ZIP/Postal Code
MD-2025
Country
Moldova, Republic of
Individual Site Status
Recruiting
Facility Name
Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz
City
Gda?sk
ZIP/Postal Code
80-214
Country
Poland
Individual Site Status
Recruiting
Facility Name
Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Neurologiczny
City
Grudzi?dz
ZIP/Postal Code
86-300
Country
Poland
Individual Site Status
Recruiting
Facility Name
MedPolonia
City
Poznan
ZIP/Postal Code
60-693
Country
Poland
Individual Site Status
Recruiting
Facility Name
Osrodek Badan Klinicznych Euromedis
City
Szczecin
ZIP/Postal Code
70-111
Country
Poland
Individual Site Status
Active, not recruiting
Facility Name
Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
City
Warszawa
ZIP/Postal Code
02-957
Country
Poland
Individual Site Status
Withdrawn
Facility Name
SPSK nr 1; Klinika Neurologii
City
Zabrze
ZIP/Postal Code
41-800
Country
Poland
Individual Site Status
Recruiting
Facility Name
Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
City
Braga
ZIP/Postal Code
4710-243
Country
Portugal
Individual Site Status
Active, not recruiting
Facility Name
ARENSIA Exploratory Medicine, County Emergency Hospital
City
Cluj-Napoca
ZIP/Postal Code
400006
Country
Romania
Individual Site Status
Recruiting

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 Study to Investigate the Safety, Tolerability, and Processing by the Body of Intravenous RO7121932 in Participants With Multiple Sclerosis.

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