TRIO: A prospective randomized Trial of non-inferiority comparing RItuximab versus Ocrelizumab in relapsing-remitting multiple sclerosis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHU De Rennes

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Jun 2023 → ongoing

Decision date (initial)

2022-12-02

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS (direction generale de l'offre de soins), PHRC (programme hospitalier recherche clinique) · DGOS (Direction generale de l'offre de soins)

External identifiers

EU CT number

2022-501027-25-01

ClinicalTrials.gov

NCT05758831

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Efficacy, Safety

To demonstrate the non-inferiority of rituximab versus ocrelizumab in active relapsing MS patients on the % of patients without disease activity at 2 years.

Secondary objectives 5

1. To compare the two groups (ocrelizumab vs rituximab) at 2 years for:  Clinical criteria: o Annualized relapse rate o Time of onset of the first relapse o % of patients without relapses o % of patients without disability progression
2. - Patients quality of life
3. - Patients experience
4. - Medico-economic impact: cost-utility ratio
5. - MRI parameters (gadolinium (Gd) enhancing lesions, new T2 lesions from M6 to M24)

Conditions and MedDRA coding

Multiple Sclerosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. - Patients presenting a relapsing remitting MS according to Mac Donald 2017 criteria, with clinical or radiological criteria of activity (ie at least one relapse AND/OR one new T2 lesion in the last 12 months before inclusion);
2. - Age between 18 and 55 years
3. - EDSS ≤ 5
4. - Brain MRI within 6 months before inclusion
5. - For women of childbearing potential: effective contraception (effective contraception include oral contraception, intrauterine devices and other forms of contraception with failure rate <1%, for the duration of the study and until 12 months after last dose administered)
6. - Having signed an informed consent form
7. - Patients covered with social insurance

Exclusion criteria 12

1. - Secondary or primary progressive MS;
2. - Contraindication to anti-CD20 therapies: • Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization • Active malignancy. • Any ongoing infection • Severe heart failure (New York Heart Association Class IV) or severe uncontrolled cardiac disease • Positive test for HIV, hepatitis B or C, or tuberculosis • Severe immune deficiency: • Lymphopenia grade 3 (0.2 to 0.5 × 10^9/L) or higher grades • Neutropenia grade 3 (0.5 to 1.0 × 10^9/L) or higher grades • Known hypersensitivity or other known side effects for any of the study medications, including co-medications such as high glucocorticosteroids • AST or ALT >=3ULN • Platelet (thrombocyte) count < 100 x 10^9/L
3. - Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty
4. - Previous treatment by mitoxantrone, cladribine, alemtuzumab and anti CD20 therapies in the last two years;
5. - Treatment with high dose corticosteroids during the 30 days preceding the inclusion;
6. - Occurrence of a relapse less than 30 days before inclusion
7. - Pregnancy or breastfeeding;
8. - Other neurologic or systemic disease;
9. - Concomitant Participation or Participation in another therapeutic trial in the last 6 months;
10. - Incapacity to understand or sign the consent form;
11. - Contraindication to MRI
12. - Previous treatment by fingolimod or natalizumab in the last 4 weeks

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. % of patients without disease activity at 2 years. Disease activity is defined as: - At least one relapse between baseline and M24 - OR MRI activity defined as Gd enhancing lesions at M6 or as the appearance of at least one new T2 lesion between M6 and M24

Secondary endpoints 6

1. Clinical criteria - Relapses: annualized relapse rate, mean time of onset of the first relapse, % of patients without relapse at M24, - Disability progression: % of patients without disability progression at M24 Disability progression will be defined as an increase of 1.5 pt if baseline EDSS=0, 1pt EDSS (if baseline 1 ≤ EDSS<6), or an increase of 0.5pt if baseline EDSS is ≥ 6; confirmed at 6 months. MRI Criteria - Mean number of Gd enhancing lesions at M6; - % of patients with at least one Gd
2. MRI Criteria - Mean number of Gd enhancing lesions at M6; - % of patients with at least one Gd enhancing lesion(s) at M6; - Mean number of new or enlarging brain T2 lesion from M6 to M24; % of patients with one or more new or enlarging brain T2 lesions from M6 to M24;
3. Quality of life - Change in the EQ5D-5L score from baseline to every six month of follow up until M24 - Change in the MusiQOL score from baseline to M12 and baseline to M24.
4. Patients experience - Change in the Musicare score from baseline to M12 and baseline to M24.
5. Medico-economic Incremental Cost-Effectiveness Ratio (ICER) defined as the cost for QALY gained in “ocrelizumab group” versus “rituximab group” at 24 months.
6. Safety - The number of each adverse event and number of severe adverse events will be compared between the two groups.

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHU De Rennes

Sponsor organisation

CHU De Rennes

Address

2 Rue Henri Le Guilloux

City

Rennes

Postcode

35000

Country

France

Scientific contact point

Organisation

CHU De Rennes

Contact name

Laure Michel

Public contact point

Organisation

CHU De Rennes

Contact name

Laure Michel

Locations

1 EU/EEA country · 26 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 13 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