Ocrelizumab VErsus Rituximab off-Label at the Onset of Relapsing MS Disease (OVERLORD-MS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Oct 2020 → ongoing

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

KLINBEFORSK

External identifiers

EU CT number

2024-510716-71-00

EudraCT number

2020-001205-23

ClinicalTrials.gov

NCT04578639

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

This is a multicenter non-inferiority study, designed to establish non-inferiority of the study treatment rituximab compared with the comparator ocrelizumab for consecutively included patients (male or female) with active relapsing-remitting multiple sclerosis aged 18-60 years.

Conditions and MedDRA coding

Multiple Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. A diagnosis of RRMS according to the revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018) within the last 12 months.
2. Treatment naïve patients aged between 18 and 60 years included
3. Disease activity defined as ≥ 1 relapse1 or ≥ 1 new MRI lesion2 during the last 12 months
4. EDSS score ≤ 4.0
5. Absence of comorbidity that preclude study participation
6. Written informed consent for study participation
7. Able to understand written and spoken Norwegian or Swedish
8. Able to complete treatment or follow-ups in the study (e.g. no contraindications for MRI, plans of moving)
9. REDUCE: Previously enrolled in and completed the OVERLORD-MS trial and OVERLORD-SWITCH study
10. REDUCE: Stable disease, defined as no relapse3 or new MRI lesion4 during the last 24 months before enrollment
11. REDUCE: Women of childbearing potential1 (WOCBP) able and willing to use highly effective methods of birth control2 that result in a low failure rate of less than 1% per year when used consistently and correctly for the duration ofmonths after last dose administered to comply with CTFG Contraception guidance Version 1.1 (CTFG 21/09/2020).
12. REDUCE: Absence of comorbidity or drug abuse that preclude study participation
13. REDUCE: Able to complete treatment or follow-up visits in the study (e.g. no contraindications for MRI or plans of moving)
14. REDUCE: . Able to understand written and spoken Norwegian or Swedish
15. REDUCE: Capable of giving signed informed consent as described in Appendix 1.2 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion criteria 8

1. A diagnosis of progressive MS according to the revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018)
2. Previous MS therapy
3. Comorbidity that is not compatible with B cell depletion therapy
4. Blood screening results (i.e. hematology, chemistry, infection) that is not compatible with B cell depletion therapy
5. Comorbidity that otherwise preclude study participation
6. Pregnancy or lactating female patients
7. REDUCE: Any disease that is a contraindication to treatment with rituximab (as described in the SMPC)
8. REDUCE: Not longer treated with rituximab (e.g. switched to another treatment for MS or stopped MStreatme

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 6 (re-baseline) to month 24
2. SWITCH: Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 24 to month 36
3. REDUCE: Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 36 to month 60 compared to the period before (month 0-36

Secondary endpoints 35

1. The annual relapse rate from baseline to month 24
2. Proportion of patients without relapses from baseline to month 24
3. Proportion of patients with progression in SDMT from baseline to month 24. Progression in SDMT is defined as patients experiencing a reduction of 15% or more from baseline (Strober, DeLuca et al. 2019, Marstrand, Osterberg et al. 2020)
4. Frequency of SAE/SAR and AESI during 24 months of treatment
5. The frequency of immediate and delayed infusion reactions during 24 months of treatment
6. The frequency of infections during 24 months of treatment
7. The frequency any malignancies during 24 months of treatment
8. Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from baseline to month 6, and from baseline to month 24
9. Proportion of patients without new gadolinium enhancing T1-weighted brain MRI lesions at month 6, month 12 and month 24
10. Change in brain volumes from baseline to month 24 and from month 6 to month 24
11. SWITCH: The annual relapse rate from month 30 to month 36
12. SWITCH: Proportion of patients without relapses from month 30 to month 36
13. SWITCH: Proportion of patients without new gadolinium enhancing T1-weighted brain MRI lesions from month 24 to month 36
14. SWITCH: Change in brain volumes from month 24 to month 36
15. SWITCH: Proportion of patients with 6-months confirmed disability progression (6M-CDP) as measured by the Expanded disability status scale (EDSS) from month 30 to month 36
16. SWITCH: Proportion of patients with 6-months confirmed disability improvement (6M-CDI) as measured by the Expanded disability status scale (EDSS) from month 30 to month 36
17. SWITCH: Proportion of patients with 6M-CDP in SDMT from month 30 to month 36
18. SWITCH: Frequency of SAE/SAR and AESI from month 30 to month 36
19. SWITCH: The frequency of immediate and delayed infusion reactions from month 30 to month 36
20. SWITCH: The frequency of infections from month 30 to month 36
21. SWITCH: The frequency any malignancies from month 30 to month 36
22. REDUCE: The annual relapse rate from month 36 to month 60
23. REDUCE: Proportion of patients without relapses from month 36 to month 60
24. REDUCE: Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 36 to month 60
25. REDUCE: Change in brain volumes from month 36 to month 60
26. REDUCE: Proportion of patients with 6-months confirmed disability progression (6M-CDP) as measured by the Expanded disability status scale (EDSS) (Kurtzke 1983) from month 36 to month 60
27. REDUCE: Proportion of patients with 6-months confirmed disability improvement (6M-CDI) as measured by the Expanded disability status scale (EDSS) (Kurtzke 1983) from month 36 to month 60
28. REDUCE: Proportion of patients with 6M-CDP in SDMT from month 36 to month 60
29. REDUCE: Frequency of SAE/SAR and AESI from month 36 to month 60
30. REDUCE: The frequency of grade 2 or above immediate and delayed infusion reactions from month 36 to month 60
31. REDUCE: The frequency of grade 2 or above infections from month 36 to month 60
32. REDUCE: The frequency any malignancies from month 36 to month 60
33. Proportion of patients with 6-months confirmed disability progression (6M-CDP) as measured by the Expanded disability status scale (EDSS) (Kurtzke 1983) from baseline to month 24.EDSS at month 24 is confirmed at month 30 (6M-CDP is defined in section 8.2.3).
34. Proportion of patients with 6-months confirmed disability improvement (6M-CDI) as measured by the Expanded disability status scale (EDSS) (Kurtzke 1983) from baseline to month 24. EDSS at month 24 is confirmed at month 30 (6M-CDI is defined in section 8.2.3)
35. SWITCH: Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 24 to month 36

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Haukelandsveien 22

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Øivind Torkildsen

Public contact point

Organisation

Helse Bergen HF

Contact name

Øivind Torkildsen

Locations

2 EU/EEA countries · 13 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 11 files

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

Application history

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