For patients with active multiple sclerosis, impact of annual versus semi-annual infusions of ocrelizumab after 2 years of initial treatment on the absence of radiological disease activity at 2 years: a multicentre randomised controlled non-inferiority trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hopital Fondation Adolphe De Rothschild

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Immune System Diseases [C20]

Trial duration

9 Nov 2023 → ongoing

Decision date (initial)

2023-07-31

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the efficacy of a treatment plan with annual administrations of ocrelizumab versus a conventional treatment plan with semi-annual administrations, on the absence of radiological disease activity at 2 years, in patients with active MS treated for at least 2 years with ocrelizumab

Secondary objectives 14

1. No incidence of relapse over the 2 years
2. The percentage of patients with no change in disability over the 2 years
3. The percentage of patients keeping no evidence of disease activity over the two years
4. The percentage of patients with at least 3 new T2 lesions at 2 years
5. The number of new T2 lesions at 24 months
6. No radiological disease activity at 12 months
7. The incidence of hypogammaglobulinemia over the two years
8. The evolution of gamma globulin levels between inclusion and 2 years
9. The evolution of the IgG level between inclusion and 2 years
10. The evolution of the IgM level between inclusion and 2 years
11. The evolution of the IgA level between inclusion and 2 years
12. The evolution of CD19 lymphocyte repopulation over the 2 years
13. The incidence of infectious events over the two years
14. Cancer incidence over the two years

Conditions and MedDRA coding

Multiple sclerosis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patient 18 years or older
2. Coming for a 4th semester cycle of ocrelizumab (at least)
3. Requires follow-up cerebral-medullary MRI as part of care
4. Who had relapsing remitting or secondarily progressive MS at the time of initiation of anti-CD20 (ocrelizumab or rituximab) therapy : relapse or radiological activity in the year priori to initiation of high-efficacy treatment
5. No relapse for at least 18 months
6. EDSS between 0 and 6 inclusive
7. Having received information about the study and having signed a consent to participate in the study
8. Knowledge of the French language
9. Affiliated or beneficiary to a social security scheme

Exclusion criteria 10

1. Clinical forms of primary progressive multiple sclerosis (PP)
2. Patients already receiving routine spacing ≥ 9 months of ocrelizumab doses
3. Contra-indication to continued treatment with ocrelizumab (hypersensitivity reaction, ongoing active infection, development of a malgnant disease since the previous inhection, development of a severe immune deficiency)
4. Planning a pregnancy within 3 years
5. Contra-indication to MRI
6. Contra-indication to the injection of contrast products
7. Subjects with severe or uncontrolled symptoms of renal, hepatic, haematological, gastrointestinal, pulmonary, psychiatric or cardiac disease or any uncontrolled intercurrent disease
8. Patient under legal protection measure
9. Patients of childbearing potential who do not wish to use effective contraception during their participation and at least 4 months after the last dose (oral commitment of the patient recorded in the medical file by the investigator)
10. Pregnant woman

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients with no new or enlarged T2 lesion >3mm on cerebro-medullary MRI at 24 months compared to inclusion MRI

Secondary endpoints 14

1. Relapse defined as the onset or worsening of symptoms, in the absence of fever, responsible for an increase of at least 0.5 points in the oberall EDSS score, or of 2 points in at least one functional systems of the EDSS, excluding sphincter and mental/cerebral scores
2. Disability progression defined as an increase of >20% in Multpile Sclerosis Functional Composite (MSFC) score between inclusion and M24. Disability progression defined by an on-study increase in EDSS score of at least 1 point from baseline if EDSS at baseline was <6, or an increase of at least 0.5 points if EDSS at baseline was equal to 6
3. Percentage of NEDA 3 patients at M24: NEDA 3 (No Evidence of disease activity) corresponds to the absence of radiological activity and clinical activity : absence of relapses and disability progression
4. Percentage of patients with at least 3 new T2 lesions on cerebro-medullary MRI at 24 months compared to the inclusion MRI
5. Number of new T2 lesions on cerebral-medullary MRI at 24 months compared to inclusion MRI
6. Percentage of patients with no new or enlarged T2 lesion >3mm on cerebro-medullary MRI at 12 months compared to inclusion MRI
7. Hypogammaglobulinemia defined as a value less than 6g/L
8. Evolution of the gamma globulin level in plasma protein eletrophoresis between inclusion and M24
9. Evolution of IgG assays between inclusion and M24.
10. Evolution of IgM assays between inclusion and M24.
11. Evolution of IgA assays between inclusion and M24.
12. Evolution of CD19 lymphocyte counts between inclusion and M24
13. Incidence of infectious events requiring treatment
14. Incidence of cancer

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hopital Fondation Adolphe De Rothschild

Sponsor organisation

Hopital Fondation Adolphe De Rothschild

Address

25 Rue Manin

City

Paris

Postcode

75019

Country

France

Scientific contact point

Organisation

Hopital Fondation Adolphe De Rothschild

Contact name

Clinical research department

Public contact point

Organisation

Hopital Fondation Adolphe De Rothschild

Contact name

Clinical research department

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 17 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