A Study to Evaluate Effectiveness and Safety of Ocrelizumab Treatment in Patients with Progressive Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 May 2018 → ongoing

Decision date (initial)

2024-03-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-506429-13-00

EudraCT number

2017-001313-93

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course

Secondary objectives 2

1. To evaluate the effectiveness of ocrelizumab treatment in PMS patients using a range of patient-relevant measures and imaging outcomes
2. To evaluate the safety and tolerability of ocrelizumab in PMS patients

Conditions and MedDRA coding

Progressive multiple sclerosis (PMS)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS or Lublin et al. 2014 criteria for PMS)
2. EDSS (Expanded Disability Status Scale) </ =6.5 at screening
3. Have a documented evidence of disability progression independent of relapse at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician's judgment
4. Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist
5. Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers
6. For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 6 months, or longer if the local label is more stringent after the last dose of study drug

Exclusion criteria 6

1. Relapsing-remitting multiple sclerosis (RRMS) at screening
2. Inability to complete an MRI
3. Gadolinium (Gd) intolerance
4. Known presence of other neurological disorders
5. Positive screening tests for hepatitis B
6. Previous treatment with B-cell targeted therapies (i.e., atacicept, tabalumab, belimumab, ofatumumab, or obinutuzumab). Note: previous treatment with rituximab is allowed as long as the last dose was administered more than 6 months before the ocrelizumab infusion AND if discontinuation was due to adverse events or

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Proportion of patients with no evidence of progression (NEP) sustained for at least 24 weeks
2. 2. Proportion of patients with NEP and no active disease (NEPAD) sustained for at least 24 weeks

Secondary endpoints 15

1. 1. Change from baseline in cognitive function as measured by the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test – Revised (BVMT-R)
2. 2. Change from baseline in the patient-reported outcomes including Multiple Sclerosis Impact Scale -29, Multiple Sclerosis Walking scale -12 items, ABILHAND-56 Questionnaire, Fatigue Scale for Motor and Cognitive (FSMC) function, SymptoMScreen, 88-item Multiple Sclerosis Spasticity Scale, Numerical Pain Rating Scale, Patient Global Impression of Severity (PGIS) for upper limb, lower limb and cognitive functions
3. 3. Mean change from baseline in the EDSS score over the course of the study
4. 4. Time to onset of first confirmed disability progression (as measured by EDSS) sustained for at least 24 and 48 weeks
5. 5. Time to onset of first >=20% increase in timed 25-foot walk test sustained for at least 24 weeks
6. 6. Time to onset of first >=20% increase in 9-hole peg test sustained for at least 24 weeks
7. 7. Proportion of patients with NEP
8. 8. Proportion of patients with NEPAD
9. 9. Proportion of patients with confirmed disability improvement (CDI) sustained for at least 24 weeks
10. 10. Change in the following MRI volumetric measures: whole brain volume, cerebral white matter volume change, cortical gray matter volume, deep grey matter volume, thalamic volumes, whole and regional cerebellar volume
11. 11. Change in the following lesion and tissue integrity parameters: - Number of new/enlarging T2 lesions and total T2 lesion volume - Number of T1 Gd+ lesions and total volume - Number of T1 lesions and total volume - Gd-enhancing fluid-attenuated inversion-recovery (FLAIR) meningeal lesions
12. 12. Rate and nature of adverse events
13. 13. Changes in clinical laboratory results
14. 14. Rates of study treatment discontinuation due to adverse events
15. 15. Change in the number of falls and near-falls

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 System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 16

Locations

7 EU/EEA countries · 34 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 28 files

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

Application history

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