A Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients with Multiple Sclerosis Previously Enrolled in A F. Hoffmann-la Roche Sponsored Ocrelizumab Clinical Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

25 Jul 2018 → 17 Jul 2025

Decision date (initial)

2023-12-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-506543-41-00

EudraCT number

2017-004886-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effectiveness of ocrelizumab therapy in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial

Secondary objectives 2

1. Different effectiveness measures evaluated for ocrelizumab in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial
2. To evaluate the safety and tolerability of ocrelizumab therapy in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial

Conditions and MedDRA coding

Multiple sclerosis (MS)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Able to comply with the study protocol, in the investigator’s judgment
2. Eligible for roll-over into the MN39158/LIBERTO study (including the female patients who were pregnant during the parent studies and are still in the safety follow up period) based on the investigator decision in a Roche sponsored ocrelizumab P-trial upon risk/benefit assessment for continuous treatment with ocrelizumab
3. Meet re-treatment criteria with ocrelizumab
4. Patients who became pregnant by chance between the last visit of the parent study and screening of this study, as confirmed by pregnancy tests at screening, will enter the safety follow-up immediately and re-start the treatment after birth and breastfeeding are over, as per re-treatment criteria
5. For women of childbearing potential: agreement to remain abstinent or use an acceptable birth control method during the treatment period and for at least 6 months or longer after the final dose of ocrelizumab, as applicable in the local ocrelizumab package leaflet

Exclusion criteria 6

1. Hypersensitivity to ocrelizumab or to any of its excipients
2. Patients in a severely immunocompromised state until the condition resolves
3. Evidence of any adverse event potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation
4. Existence of a contra-indication as per ocrelizumab package leaflet
5. Prohibited concomitant medication use
6. Patients intending to become pregnant during the study or within 6 months after the last dose of the study drug in the parent study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Evaluate clinical measures related to disease progression over the duration of treatment in MS patients

Secondary endpoints 26

1. 1. Related to disability progression: Time to onset of Confirmed disability progression (CDP) sustained for at least 24 weeks and for at least 48 weeks
2. 2. Related to disability progression: Proportion of patients who have confirmed disability improvement (CDI), CDP for at least 24 weeks and for at least 48 weeks yearly and over the duration of treatment
3. 3. Related to disability progression: Proportion of patients who have improved, stable or worsened disability compared with baseline (inclusion in the study) measured by expanded disability status scale (EDSS)
4. 4. Related to disability progression: Mean change from inclusion in the parent study in EDSS score over the course of treatment
5. 5. Related to disability progression: Time to 20% increase in timed 25-foot walk test (T25FWT); time to 20% increase in timed nine-hole peg test (9HPT) sustained for at least 24 weeks and for at least 48 weeks, and proportion of patients achieving a sustained increase assessed yearly and over the duration of treatment
6. 6. Other clinical measures and composite endpoints: Time to first protocol-defined event of disease activity
7. 7. Other clinical measures and composite endpoints: Time to first relapse
8. 8. Other clinical measures and composite endpoints: Annualized relapse rate
9. 9. Other clinical measures and composite endpoints: Proportion of patient relapse free, yearly and over the course of treatment
10. 10. Other clinical measures and composite endpoints: Proportion of patients with no evidence of protocol-defined disease activity (NEDA) yearly and over the duration of the treatment
11. 11. Other clinical measures and composite endpoints: Proportion of patients with no evidence of progression, measured by EDSS, 9HPT and T25FW (if assessments are available)
12. 12. Other clinical measures and composite endpoints: Proportion of patients with no evidence of progression sustained for at least 24 weeks and no active disease (if assessments are available)
13. 13. Other clinical measures and composite endpoints: Change from baseline (parent trial) in cognitive performance as measured by the Symbol digit modalities test (SDMT)
14. 14. Related to MRI: Total number of T1 Gd-enhancing lesions as detected by brain MRI over time
15. 15. Related to MRI: Total number of new and/or enlarging T2 lesion as detected by brain MRI over time
16. 16. Related to MRI: Change in total T1 hypointense lesion volume over time
17. 17. Related to MRI: Total number of fluid-attenuated inversion-recovery (FLAIR) late enhancing lesions as detected by brain MRI over time (pertinent to CASTING/MA30005 patients only)
18. 18. Related to MRI: Total number of FLAIR late enhancing lesions as detected by brain MRI at the end of the treatment period
19. 19. Related to MRI: Change in brain volume (including white and grey matter fractions) as detected by brain MRI over time
20. 20. Related to MRI: Presence and evolution of leptomeningeal follicles (pertinent to ENSEMBLE/MA30143 patients with identified FLAIR late enhancing lesions and CASTING /MA30005 patients)
21. 21. Other measures related to MS disease:Time to treatment discontinuation/switch
22. 22. Patient reported outcomes (PROs):Employment status (Work Productivity and Activity Impairment Questionnaire [WPAI])
23. 23. Patient reported outcomes (PROs):SymptoMScreen score
24. 24. Patient reported outcomes (PROs):Quality of life (Multiple Sclerosis Impact Scale [MSIS]-29)
25. 25. Rate and nature of adverse events
26. 26. Changes in vital signs, neurological examinations, clinical laboratory results, locally reviewed MRI for safety (non-MS CNS pathology) and concomitant medications

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information Support Line - TISL

Third parties 8

Locations

14 EU/EEA countries · 55 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 76 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications