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

Phase 3
Active, not recruiting
Conditions
Relapsing-Remitting Multiple Sclerosis
Registration Number
2023-506516-40-00
Lead Sponsor
F. Hoffmann-La Roche AG
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruitment ended
Sex
Not specified
Target Recruitment
94
Inclusion Criteria

Age between 10 to <18 years at randomization with Body weight >=25 kilograms

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

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

Children and adolescents must have received all childhood vaccinations as per local and/or national recommendations for childhood vaccination against infectious diseases

Expanded disability status scale (EDSS) at screening: 0-5.5, both inclusive

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

Aquaporin-4 positive and/or myelin oligodendrocyte glycoprotein antibody positive

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

Receipt of any type of vaccine (e.g., live or live-attenuated vaccine, non-live) within 6 weeks prior to treatment allocation

History of symptomatic bradycardia, recurrent syncope, significant QT prolongation, Patients with severe cardiac arrhythmias

Exclusion criteria related to prior treatments for MS, as per protocol

Exclusion Criteria Related to Laboratory Findings, as per protocol

Study & Design

Study Type
Not specified
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
1. Protocol-defined annualized relapse rate (ARR) (non-inferiority)

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

Secondary Outcome Measures
NameTimeMethod
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)

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)

9. Prevalence of anti-drug antibodies (ADAs) against ocrelizumab at baseline

9. Prevalence of anti-drug antibodies (ADAs) against ocrelizumab at baseline

1. Number of new or enlarging T2 lesions as detected by brain MRI during the double-blind period

1. Number of new or enlarging T2 lesions as detected by brain MRI during the double-blind period

2. Number of T1 gadolinium (Gd) lesions at Week 12

2. Number of T1 gadolinium (Gd) lesions at Week 12

3. Protocol-defined ARR during the double-blind period (superiority)

3. Protocol-defined ARR during the double-blind period (superiority)

5. Change from baseline in targeted vital signs and clinical significant abnormalities in electrocardiogram (ECG) parameters

5. Change from baseline in targeted vital signs and clinical significant abnormalities in electrocardiogram (ECG) parameters

6. Change from baseline in targeted clinical laboratory test results

6. Change from baseline in targeted clinical laboratory test results

7. Concentrations of ocrelizumab at indicated time points

7. Concentrations of ocrelizumab at indicated time points

8. Levels of CD19 B-cell count in blood

8. Levels of CD19 B-cell count in blood

10. Incidence of ADAs against ocrelizumab during the study

10. Incidence of ADAs against ocrelizumab during the study

Trial Locations

Locations (42)

University Hospital Consorziale Policlinico

🇮🇹

Bari, Italy

Ospedale Pediatrico Bambino Gesu'

🇮🇹

Rome, Italy

Università degli Studi "Gabriele d'Annunzio" - Center for Advanced Studies and Technology (CAST)

🇮🇹

Chieti, Italy

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania

🇮🇹

Catania, Italy

IRCCS Foundation Istituto Neurologico Carlo Besta

🇮🇹

Milan, Italy

Azienda Ospedaliero-Universitaria Sant Andre

🇮🇹

Rome, Italy

Vestische Kinder- und Jugendklinik Datteln

🇩🇪

Datteln, Germany

Technische Universitat Dresden

🇩🇪

Dresden, Germany

Hospital Universitario Virgen De La Macarena

🇪🇸

Sevilla, Spain

Sant Joan De Deu Barcelona Hospital

🇪🇸

Esplugues De Llobregat, Spain

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University Hospital Consorziale Policlinico
🇮🇹Bari, Italy
Pietro Iaffaldano
Site contact
+390805593604
pietro.iaffaldano@uniba.it

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