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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— BLOOMS  

Official title:

Efficacy, Safety and Cost-effectiveness of B Cell Tailored Ocrelizumab Versus Standard Ocrelizumab in Relapsing Remitting Multiple Sclerosis: a Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296161
• Other study ID #: 2021.0639
• Status: Recruiting
• Phase: Phase 4
• Start date: April 20, 2022
• Est. completion date: March 2026

Study information

• Verified date: April 2022
• Source: Amsterdam UMC, location VUmc
• Contact: Laura Hogenboom, Msc
• Phone: 01204440717
• Email: l.hogenboom1[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 296
• Est. completion date: March 2026
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• Previous treatment with alemtuzumab, cladribine or stem cell transplantation
• Relapse in the past 3 months prior to inclusion
• Subsequent treatment with another DMT next to ocrelizumab in the past 6 months prior to inclusion
• Inability to undergo regular MRI scanning
• Women who are pregnant or expect to become pregnant during the study period

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Ocrelizumab
Personalized B cell tailored ocrelizumab treatment

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC, location VU	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Trough ocrelizumab concentration	in serum	24 weeks, 48 weeks, 72 weeks, 96 weeks
Other	Intra-individual course and stability B-cell counts and subsets from whole blood	In a subgroup of patients cell subsets including CD4+ T cells, CD8+ T cells, CD20+ T cells, CD3-D56+ NK cells, and various B cell subsets (CD19+CD27- naive B cells, CD19+CD27+ memory B cells, CD19+CD27+IgD-IgM- switched memory B cells and CD19+CD27+IgD+ marginal zone B cells) will be tested.	24 weeks, 48 weeks, 72 weeks, 96 weeks
Primary	Confirmed relapse-free patients	Difference of percentage of confirmed relapse-free patients between the two treatment groups after 96 weeks follow-up.	96 weeks
Primary	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	Annualized relapse rate	Clinical relapses during B-cell tailored dosing	Baseline, year 1, year 2
Secondary	Total number of active (new and/or enlarging) T2 lesions on brain MRI	In comparison to the baseline MRI and number of active MRI scans.	Baseline, year 1, year 2
Secondary	Disability progression during follow-up	Disability progression measured on the Expanded Disability Status Scale (EDSS)	Baseline, 6 months,12 months, 18 months, 24 months
Secondary	Disability progression during follow-up	Disability progression measured on the Expanded Disability Status Scale (EDSS)	Baseline, year 1, year 2
Secondary	Brain atrophy	Rate of brain atrophy comparing baseline MRI and MRI at 96 weeks.	Baseline, year 1, year 2
Secondary	NEDA (no evidence of disease activity)	NEDA is defined as absence of confirmed relapses, MRI disease activity (new/enlarging T2 lesions) and confirmed disability progression.	96 weeks
Secondary	Change of neurofilament light	Measured in serum	96 weeks
Secondary	Change of quality of life	Measured by the Multiple Sclerosis Impact Scale (MSIS-29)	Baseline, year 1, year 2
Secondary	Change of burden of treatment	measured by the Treatment Satisfaction Questionnaire for Medication (TSQM)	Baseline, year 1, year 2
Secondary	Ocrelizumab wearing-off effect	Presence of a possible wearing-off effect measured by a questionnaire developed by the Amsterdam MS Center	Baseline, year 1, year 2
Secondary	IgG levels	Change of IgG levels	Baseline, year 1, year 2
Secondary	Cost analysis	Cost-utility analysis using EuroQol 5D (EQ-5D)	96 weeks
Secondary	Disability progression: decrease of hand mobility	Significant decrease of hand mobility measured by an app that analyses key stroke dynamics. The dynamics are measured continuously and analysed every 6 months.	Baseline, 6 months,12 months, 18 months, 24 months
Secondary	Disability progression: two minute walking distance	Significant decrease of walking distance measured by an app that analyses distance using GPS signal. The test is taken monthly and analysed every 6 months.	Baseline, 6 months,12 months, 18 months, 24 months
Secondary	Disability progression: cognitive impairment	Significant decrease of cognitive impairment measured by an app that is validated for a digital Symbol Digit Modalities Test (SDMT). The test is taken monthly and analysed every 6 months.	Baseline, 6 months,12 months, 18 months, 24 months