A Study to Evaluate the Effects of Ocrelizumab on Immune Responses In Participants With Relapsing Forms of Multiple Sclerosis

February 29, 2024 updated by: Hoffmann-La Roche

A Phase IIIB, Multicenter, Randomized, Parallel-Group, Open-Label Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Patients With Relapsing Forms of Multiple Sclerosis

This multicenter, randomized, open-label study will evaluate the immune response to vaccines (tetanus toxoid [TT]-containing adsorbed vaccine, 23-valent pneumococcal polysaccharide vaccine [23-PPV] either unboosted or boosted with 13-valent pneumococcal conjugate vaccine [13-PCV], influenza vaccine, keyhole limpet hemocyanin [KLH]) after administration of a dose of ocrelizumab (OCR) in participants with relapsing multiple sclerosis (RMS).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • University of Calgary
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 2B5
        • University of British Columbia Hospital; Division of Neurology
  • United States
    • Alabama
      • Cullman, Alabama, United States, 35058
        • North Central Neurology Associates
    • Arizona
      • Tucson, Arizona, United States, 85704
        • Territory Neurology and Research Institute
    • California
      • Fullerton, California, United States, 92835
        • Fullerton Neurology and Headache Center
      • La Jolla, California, United States, 92037
        • Scripps Clinic
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center
      • Tampa, Florida, United States, 33612
        • University of South Florida
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Michigan Institute for Neurological Disorders
    • Minnesota
      • Golden Valley, Minnesota, United States, 55422
        • The Minneapolis Clinic of Neurology
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Mercy Hospital St. Louis / Mercy Clinic Neurology
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Cleveland Clinic Lou Ruvo; Center for Brain Research
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico
    • New York
      • Staten Island, New York, United States, 10306
        • Staten Island Univ Hospital
    • North Carolina
      • Hickory, North Carolina, United States, 28602
        • Neurology Associates PA
    • Ohio
      • Columbus, Ohio, United States, 43214
        • Ohio Health Research Institute Grant Medical Center
      • Westerville, Ohio, United States, 43082
        • MDH Research LLC
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Neurological Associates
    • Tennessee
      • Cordova, Tennessee, United States, 38018
        • Neurology Clinic PC
    • Texas
      • Round Rock, Texas, United States, 78681
        • Central Texas Neurology Consultants
    • Utah
      • Salt Lake City, Utah, United States, 84103
        • Rocky Mountain MS Clinic
    • Washington
      • Seattle, Washington, United States, 98104-1360
        • Swedish Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of RMS in accordance with the revised McDonald criteria
  • Received at least one previous immunization against TT or tetanus and diphtheria (DT/Td) or tetanus, diphtheria, and acellular pertussis (DTaP/Tdap)
  • Expanded Disability Status Scale (EDSS) at Screening from 0 to 5.5 points, inclusive
  • For sexually active female participants of reproductive potential, use of reliable means of contraception

Exclusion Criteria:

  • Contraindications for or intolerance to oral or IV corticosteroids, including IV methylprednisolone, according to the country label
  • Known presence of other neurologic disorders
  • Treatment with any investigational agent within 24 weeks of screening or 5 half-lives of the investigational drug, whichever is longer, or treatment with any experimental procedure for multiple sclerosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
Biological: 23-PPV
The 23-PPV vaccine will be given as a 0.5-milliliter (mL) intramuscular (IM) injection in the deltoid muscle on Day 112 (Group A) or Day 28 (Group B).
Biological: 13-PCV Booster
The 13-PCV booster will be given as an IM injection in the deltoid muscle on Day 140 (select participants in Group A).
Biological: Influenza Vaccine
The influenza vaccine will be given as an IM injection in the deltoid muscle at any time between Day 85 and Day 144 (select participants in Group A) or any time between Day 1 and Day 85 (Group B).
Biological: KLH
KLH will be given as a 1-mg subcutaneous (SC) injection on Days 84, 112, and 140 (Group A) or Days 1, 28, and 56 (Group B).
Drug: OCR
OCR will be given as an intravenous (IV) infusion at a dose of 600 mg, with the first dose given as two infusions of 300mg 14 days apart, according to the specifications described in the corresponding Group A and Group B arms.
Other Names:
  • RO4964913, PRO70769, rhuMAb 2H7
Biological: TT Vaccine
The TT-containing adsorbed vaccine will be given as a 0.5-mL IM injection in the deltoid muscle on Day 85 (Group A) or Day 1 (Group B).
Other: Group B: Vaccines (Optional OCR in Extension)
Participants will receive immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization period.
Biological: 23-PPV
The 23-PPV vaccine will be given as a 0.5-milliliter (mL) intramuscular (IM) injection in the deltoid muscle on Day 112 (Group A) or Day 28 (Group B).
Biological: Influenza Vaccine
The influenza vaccine will be given as an IM injection in the deltoid muscle at any time between Day 85 and Day 144 (select participants in Group A) or any time between Day 1 and Day 85 (Group B).
Biological: KLH
KLH will be given as a 1-mg subcutaneous (SC) injection on Days 84, 112, and 140 (Group A) or Days 1, 28, and 56 (Group B).
Drug: OCR
OCR will be given as an intravenous (IV) infusion at a dose of 600 mg, with the first dose given as two infusions of 300mg 14 days apart, according to the specifications described in the corresponding Group A and Group B arms.
Other Names:
  • RO4964913, PRO70769, rhuMAb 2H7
Biological: TT Vaccine
The TT-containing adsorbed vaccine will be given as a 0.5-mL IM injection in the deltoid muscle on Day 85 (Group A) or Day 1 (Group B).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine
Time Frame: 8 weeks after TT vaccine
For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 8 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 8 weeks after vaccination compared with pre-vaccination levels.
8 weeks after TT vaccine

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Positive Response to TT Vaccine Measured 4 Weeks After TT Vaccine
Time Frame: 4 weeks after TT vaccine
For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.
4 weeks after TT vaccine
Percentage of Participants With Tetanus Antibody Titer >/=0.2 IU/mL or 2-Fold Increase in Tetanus Antibody Titers
Time Frame: 4 weeks after TT vaccine
For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 2-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.
4 weeks after TT vaccine
Mean Levels of Anti-Tetanus Antibody
Time Frame: Immediately prior to and at 4 and 8 weeks after TT vaccine
Anti-tetanus antibody levels were assessed by enzyme-linked immunosorbent assay (ELISA).
Immediately prior to and at 4 and 8 weeks after TT vaccine
Mean Levels of Anti-KLH Antibody: Immunoglobulin (Ig) G
Time Frame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
Anti-KLH antibody levels were assessed by ELISA.
Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
Mean Levels of Anti-KLH Antibody: Ig M
Time Frame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
Anti-KLH antibody levels were assessed by ELISA.
Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 23-PPV
Time Frame: 4 weeks after 23-PPV
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or greater than (>) 1 microgram per milliliter (mcg/mL) rise compared with pre-vaccination levels.
4 weeks after 23-PPV
Percentage of Participants With Positive Response Against >/=2 Pneumococcal Serotypes
Time Frame: 4 weeks after 23-PPV
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.
4 weeks after 23-PPV
Percentage of Participants With Positive Response Against >/=12 Pneumococcal Serotypes
Time Frame: 4 weeks after 23-PPV
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.
4 weeks after 23-PPV
Mean Levels of Anti-Pneumococcal Antibody
Time Frame: Immediately prior to and 4 weeks after 23-PPV
Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).
Immediately prior to and 4 weeks after 23-PPV
Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 13-PCV
Time Frame: 8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.
8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV
Mean Level of Anti-Pneumococcal Antibody
Time Frame: Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV
Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).
Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV
Percentage of Participants With Seroprotection
Time Frame: 4 weeks after seasonal influenza vaccine administration
Seroprotection was defined as specific hemagglutination inhibition (HI) titers >40 at 4 weeks after vaccination.
4 weeks after seasonal influenza vaccine administration
Percentage of Participants With 2-Fold Increase in Strain-Specific HI Titers
Time Frame: 4 weeks after seasonal influenza vaccine administration
2-fold increase from prevaccination HI titer.
4 weeks after seasonal influenza vaccine administration
Percentage of Participants With 4-Fold Increase in Strain-Specific HI Titers
Time Frame: 4 weeks after seasonal influenza vaccine administration
4-fold increase from prevaccination HI titer.
4 weeks after seasonal influenza vaccine administration
Percentage of Participants With Seroconversion
Time Frame: 4 weeks after influenza immunization
Seroconversion at 4 weeks after vaccination defined, as per protocol, as a prevaccination HI titer <10 and an HI titer >40 at 4 weeks after vaccination. Seroconversion at 4 weeks after vaccination, defined per FDA guidance, as either a) a pre-vaccination HI titer <10 and HI titer >/= 40 at 4 weeks after vaccination, or b) a pre-vaccination HI titer >/= 10 and at least 4-fold increase in HI antibody titer at 4 weeks after vaccination.
4 weeks after influenza immunization
Strain-Specific Geometric Mean Titer Levels
Time Frame: Baseline and Week 4
Geometric mean titers (GMTs) in participants in Groups A2 and B were measured 4 weeks after vaccination.
Baseline and Week 4
Ratio of Strain-Specific Geometric Mean Titer Levels Postvaccination to Prevaccination
Time Frame: Immediately prior to and 4 weeks after influenza vaccine
Strain-specific GMT ratios were calculated as post-vaccination : pre-vaccination.
Immediately prior to and 4 weeks after influenza vaccine
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Number of T2 Lesions
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Categorical Number of T2 Lesions
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Number of Gadolinium (Gd)-Enhancing T1 Lesions
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Categorical Number of Gd-enhancing T1 Lesions
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Normalized Brain Volume
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Volume of T2 Lesions: White Matter Volume
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Cortical Grey Matter Volume
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: T1 Unenhancing Lesion Volume
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
MRI Parameters: Total Number of Lesions
Time Frame: Baseline
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Baseline
Cellular Immune Response Assessed by Flow Cytometry
Time Frame: Days 1, 15, 85, 112, 140 and 169

Flow cytometry is a laser-based technology commonly used for cell counting and sorting. In this study, this outcome measure is focusing on a single variable, CD19 count (total B cells). LLN = 80 cells/ul.

Repleted is defined as CD19 >= LLN or baseline, whichever is lower.
Days 1, 15, 85, 112, 140 and 169
Total Immunoglobulin
Time Frame: Days 1, 85, and 169
Days 1, 85, and 169
Percentage of Participants With Anti-Drug Antibody Formation
Time Frame: Up to 24 Weeks (ISP)
Anti-Drug Antibodies (ADA) may induce unwanted side effects, especially in biotechnology-derived pharmaceuticals, such as therapeutic antibodies and growth factors.
Up to 24 Weeks (ISP)
Percentage of Participants With Adverse Events (AEs), Serious AEs, or AEs Leading to Study Discontinuation
Time Frame: During ISP (24 weeks for Group A and 12 weeks for Group B)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious AE is any AE that is fatal, life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug, or is a significant medical event in the investigator's judgment.
During ISP (24 weeks for Group A and 12 weeks for Group B)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 27, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 14, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 21, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 8, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 29, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BN29739
  • 2015-001357-32 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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