A Study to Evaluate Safety and Efficacy of Ocrelizumab in Comparison with Fingolimod in Children and Adolescents with Relapsing-Remitting Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

11 Feb 2022 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-506516-40-00

EudraCT number

2020-004128-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Others, Safety, Pharmacokinetic

To demonstrate non-inferiority of ocrelizumab compared with fingolimod, based on Protocol-defined annualized relapse rate (ARR)

Secondary objectives 6

1. To demonstrate non-inferiority of ocrelizumab compared with fingolimod based on the number of new or enlarging T2-hyperintense lesions (T2 lesions) as detected by brain MRI
2. To demonstrate the superiority of ocrelizumab versus fingolimod based on the number of new or enlarging T2-hyperintense lesions, number of T1 gadolinium lesions and protocol-defined ARR
3. To evaluate the safety of ocrelizumab administered by intravenous (IV) infusion every 24-weeks compared with fingolimod administered once a day (QD) by mouth (PO)
4. To assess the pharmacokinetics of ocrelizumab in all children/adolescents enrolled in this study
5. To assess the pharmacodynamics in all children/adolescents enrolled in this study, as measured by blood B-cell count
6. To evaluate the immune response to ocrelizumab

Conditions and MedDRA coding

Relapsing-Remitting Multiple Sclerosis

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age between 10 to <18 years at randomization with Body weight >=25 kilograms
2. At least one relapse during the year prior to screeningAt least one relapse during the year prior to screening or two relapses in the previous two years prior to screening or evidence of at least one Gd enhancing lesion on MRI within 6 months prior to randomization (including screening MRI) For Germany, the criterion is as follows: Highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy, or patients with rapidly evolving severe RRMS defined by 2 or more disabling relapses in one year, and with at least one Gadolinium enhancing lesion on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI or two relapses in the previous two years prior to screening or evidence of at least one Gd enhancing lesion on MRI within 6 months prior to randomization (including screening MRI) For Germany, the criterion is as follows: Highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy, or patients with rapidly evolving severe RRMS defined by 2 or more disabling relapses in one year, and with at least one Gadolinium enhancing lesion on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI
3. Diagnosis of relapsing-remitting multiple sclerosis (RRMS) in accordance with the international pediatric multiple sclerosis study group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017 (or the most current revision of the IPMSSG criteria or McDonald criteria at the time of study start) and confirmed by the Independent Pediatric MS Review Committee prior to randomization
4. Children and adolescents must have received all childhood vaccinations as per local and/or national recommendations for childhood vaccination against infectious diseases
5. Expanded disability status scale (EDSS) at screening: 0-5.5, both inclusive
6. Female patients of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 24 weeks after the final dose of ocrelizumab/ocrelizumab placebo and for 2 months after the final dose of fingolimod/fingolimod placebo

Exclusion criteria 6

1. Aquaporin-4 positive and/or myelin oligodendrocyte glycoprotein antibody positive
2. Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to Day 1 visit or oral anti-infective agents within 2 weeks prior to Day 1 visit or History or known presence of recurrent or chronic infection
3. Receipt of any type of vaccine (e.g., live or live-attenuated vaccine, non-live) within 6 weeks prior to treatment allocation
4. History of symptomatic bradycardia, recurrent syncope, significant QT prolongation, Patients with severe cardiac arrhythmias
5. Exclusion criteria related to prior treatments for MS, as per protocol
6. Exclusion Criteria Related to Laboratory Findings, as per protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Protocol-defined annualized relapse rate (ARR) (non-inferiority)

Secondary endpoints 10

1. 1. Number of new or enlarging T2 lesions as detected by brain MRI during the double-blind period
2. 2. Number of T1 gadolinium (Gd) lesions at Week 12
3. 3. Protocol-defined ARR during the double-blind period (superiority)
4. 4. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
5. 5. Change from baseline in targeted vital signs and clinical significant abnormalities in electrocardiogram (ECG) parameters
6. 6. Change from baseline in targeted clinical laboratory test results
7. 7. Concentrations of ocrelizumab at indicated time points
8. 8. Levels of CD19 B-cell count in blood
9. 9. Prevalence of anti-drug antibodies (ADAs) against ocrelizumab at baseline
10. 10. Incidence of ADAs against ocrelizumab during the study

Investigational products

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

Test 1

Comparator 4

Placebo 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 12

Locations

17 EU/EEA countries · 41 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

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 338 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