B Cell Tailored Ocrelizumab Versus Standard Ocrelizumab in Relapsing Remitting Multiple Sclerosis

NCT05296161 | Recruiting Phase 4 DMC

• 1 other identifier: 2021.0639
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: B-cell depleting therapies like ocrelizumab are very effective in the treatment of relapsing remitting multiple sclerosis (RRMS). As B cell repopulation varies extensively between individuals (ranging from 27-175 weeks), using a treatment scheme with a fixed infusion interval may be suboptimal. So far personalized adapted treatment of ocrelizumab in RRMS has not been studied in a prospective setting. Objective: Evaluating the efficacy, safety and cost-effectiveness of ocrelizumab when administered in personalized B cell tailored intervals in RRMS patients. Study design: This is a national multicenter randomized controlled trial with 96 week follow-up. Study population: The study population consists of 296 adult RRMS patients who have received ocrelizumab treatment for a minimum of 12 months (2x 300 mg infusion and 1x 600mg infusion). Intervention: Patients will be randomized into the standard interval group (600 mg infusions every 24 weeks) or the personalized interval group in which the infusions will be extended as long as the serum CD19 B cell count is below 10 CD19 cells/µL, determined every 4 weeks. Main study parameters: To conclude non-inferiority of personalized B cell tailored ocrelizumab there will be two co-primary endpoints: 1. the difference of percentage of confirmed relapse-free patients between the two groups after 96 weeks and 2. the difference of percentage of patients free from new/enlarging T2 lesions on MRI between the two groups after 96 weeks. Secondary study parameters are number of confirmed relapses, annualized relapse rate, number of new T2 lesions and brain atrophy on MRI, disability progression, no evidence of disease activity (NEDA), MS disease biomarkers (serum neurofilament light), quality of life, burden of treatment, immunoglobulin levels and (serious) adverse events including occurrence of infections and COVID-19. Furthermore, various immune cell subsets will be studied in relation to ocrelizumab concentration in a subgroup. Nature and extent of the burden and risks: All patients will be subjected to visits every 24 weeks including clinical scoring and questionnaires. Blood samples and MRI scans will be taken and performed every 48 weeks. Continuous assessment of key stroke dynamics on the patients smartphone and monthly digital cognitive test and walk test will be performed in most patients. As CD19 B cells are kept near complete depletion, the estimated risk of recurrence of disease activity is very low.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

ocrevus; ocrelizumab; personalised dosing

Outcome Measures

Primary Outcomes (2)

• Confirmed relapse-free patients

  Difference of percentage of confirmed relapse-free patients between the two treatment groups after 96 weeks follow-up.

  96 weeks

• Change of T2 lesions on brain MR

  Difference of percentage of patients without new/enlarging T2 MRI lesions between the two treatment groups after 96 weeks follow-up.

  96 weeks

Secondary Outcomes (15)

• Annualized relapse rate

  Baseline, year 1, year 2

• Total number of active (new and/or enlarging) T2 lesions on brain MRI

  Baseline, year 1, year 2

• Disability progression during follow-up

  Baseline, 6 months,12 months, 18 months, 24 months

• Disability progression during follow-up

  Baseline, year 1, year 2

• Brain atrophy

  Baseline, year 1, year 2

Other Outcomes (2)

• Trough ocrelizumab concentration

  24 weeks, 48 weeks, 72 weeks, 96 weeks

• Intra-individual course and stability B-cell counts and subsets from whole blood

  24 weeks, 48 weeks, 72 weeks, 96 weeks

Study Arms (2)

Standard interval dosing

NO INTERVENTION

The standard group will receive ocrelizumab every 24 weeks following the current label.

Personalized B cell tailored ocrelizumab treatment

EXPERIMENTAL

The personalized group will start with B cell measurements 24 weeks after the last infusion (baseline). The infusion interval will never be shorter than 24 weeks. The personalized group will start the study with a possible extension of the interval. The infusion will be postponed as long as CD19 B cell count stays below 10 cells/µL (determined every 4 weeks). When CD19 B cell count exceeds or is equal to 10 cells/µL, ocrelizumab infusion will be scheduled within two weeks

Drug: Ocrelizumab

Interventions

Ocrelizumab DRUG

Personalized B cell tailored ocrelizumab treatment

Also known as: ocrevus

Personalized B cell tailored ocrelizumab treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A current diagnosis of relapsing remitting multiple sclerosis according to the 2017 McDonald criteria34
• EDSS score of 0 to 6.5
• Treatment with ocrelizumab for a minimum of 48 weeks (two 300 mg infusions and one 600 mg infusion)

You may not qualify if:

• Previous treatment with alemtuzumab, cladribine or stem cell transplantation
• Inability to undergo regular MRI scanning
• Women who are pregnant or expect to become pregnant during the study period

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam UMC, location VU

Amsterdam, North Holland, 1081 HV, Netherlands

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Joep Killestein, Prof.

  Amsterdam UMC, location VU

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Hogenboom, Msc

CONTACT

01204440717; l.hogenboom1@amsterdamumc.nl

Zoé van Kempen, Dr.

CONTACT

0204442182; z.vankempen@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Multicenter randomized controlled non-inferiority trial in The Netherlands

Study Record Dates

• First Submitted: February 18, 2022
• First Posted: March 25, 2022
• Study Start: April 20, 2022
• Primary Completion: April 1, 2024
• Study Completion: March 1, 2026
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After medical ethical commitee approved the study protocol.

Locations

NL (1)