A MULTICENTER, RANDOMIZED, DOUBLE-BLIND DOUBLE-DUMMY PHASE III STUDY TO ASSESS THE SAFETY AND EFFICACY OF OCRELIZUMAB COMPARED TO FINGOLIMOD IN CHILDREN AND ADOLESCENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

ICTRP Studien-ID
EUCTR2020-004128-41 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY STUDY TO EVALUATE SAFETY AND EFFICACY OF OCRELIZUMAB IN COMPARISON WITH FINGOLIMOD IN CHILDREN AND ADOLESCENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS (BASEC)

Wissenschaftlicher Titel
A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY STUDY TO EVALUATE SAFETY AND EFFICACY OF OCRELIZUMAB IN COMPARISON WITH FINGOLIMOD IN CHILDREN AND ADOLESCENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS (ICTRP)

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

Untersuchte Krankheit(en)
Relapsing-Remitting Multiple Sclerosis
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)

Untersuchte Intervention

Trade Name: Ocrevus
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Gilenya
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Fingolimod
CAS Number: 162359-55-9
Current Sponsor code: RO7079904
Other descriptive name: FINGOLIMOD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

(ICTRP)

Studientyp
Interventional clinical trial of medicinal product (ICTRP)

Studiendesign
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2 (ICTRP)

Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes

Inclusion criteria:
General Inclusion Criteria
? Able to comply with the study protocol, in the investigator's judgment
? Age between >10 to <18 years at randomization
? Body weight >=25 kilograms
? Children and adolescents must have received all childhood vaccinations as per local and/or national recommendations for childhood vaccination against infectious diseases
? 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
Inclusion Criteria Related to Pediatric Multiple Sclerosis
? 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)
? Confirmation of the diagnosis of Pediatric RRMS by the Independent Pediatric MS Review Committee prior to randomization
? Expanded disability status scale (EDSS) at screening: 0-5.5, both inclusive
? Neurologic stability for >=30 days prior to screening, and between screening and Day 1
? At 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)
Are the trial subjects under 18? yes
Number of subjects for this age range: 233
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)

Exclusion criteria:
Exclusions Related to General Health
? Pregnancy or lactation
? Known presence or suspicion of other neurologic disorders that may mimic MS
? Aquaporin-4 positive and/or myelin oligodendrocyte glycoprotein antibody positive at screening
? Clinical or laboratory findings at first presentation not typically for MS
? Abnormal findings in the cerebrospinal fluid at first presentation
? Atypical magnetic resonance imaging (MRI) findings
? Significant uncontrolled somatic diseases or any other significant condition
? Known active bacterial, viral, fungal, mycobacterial infection, or other infection
? 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
? 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 or laboratory evidence of clinically significant coagulation disorders
? Peripheral venous access that precludes IV administration and venous blood sampling
? Inability to complete MRI scan
? Teeth braces interfering with MRI acquisition
? History of cancer
? Currently active or history of alcohol or drug abuse
Exclusion Criteria Related to General Health Specific to Fingolimod Treatment
? History of symptomatic bradycardia, recurrent syncope, significant QT prolongation.
? Patients who in the previous 6 months had myocardial infarction, unstable angina pectoris, stroke/transient ischemic attack, decompensated heart failure, or New York Heart Association Class III/IV heart failure
? Patients with severe cardiac arrhythmias
? Patients with second-degree Mobitz type II atrioventricular (AV) block or third-degree AV block, sick-sinus syndrome or sinoatrial heart block
? Patients with a baseline QTc interval >=500 milliseconds
? Presence of macular edema
? Presence of any pulmonary conditions, as determined by the investigator
? History of any type of epileptic seizure(s) as well as psychogenic non-epileptic seizure(s) during the past 12 months before screening
? Patients with chronic liver or biliary disease, acute or chronic pancreatitis
Exclusion Criteria Related to Medications
? History of a severe allergic or anaphylactic reaction to humanized or murine MAbs or known hypersensitivity to any component of ocrelizumab solution
? Contraindications to or intolerance of oral or IV corticosteroids, antihistamines, or antipyretics
? Treatment with any investigational agent within 24 weeks of screening or 5 half-lives
? Previous treatment with B-cell-targeted therapies
? Any previous treatment with alemtuzumab, anti-CD4, cladribine, mitoxantrone, daclizumab, laquinimod, total body irradiation, or bone marrow transplantation
? Treatment with cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, or methotrexate within 24 months prior to treatment allocation
? Treatment with natalizumab within 12 months prior to randomization
? Previous treatment with fingolimod
? Treatment with teriflunomide within 24 weeks prior to treatment allocation or 4 weeks prior to treatment allocation if an accelerated elimination procedure is completed (with confirmation of drug plasma level of < 0.02mg/ml) or any other S1P receptor modulator within 24 weeks prior to treatment allocation
? Treatment with dimethyl fumarate within 4 weeks prior to treatment allocation
? Treatment with

Primäre und sekundäre Endpunkte
Main Objective: ? To demonstrate non-inferiority of ocrelizumab compared with fingolimod, based on Protocol-defined annualized relapse rate (ARR);Secondary Objective: ? 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
? 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
? 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)
? To assess the pharmacokinetics of ocrelizumab in all children/adolescents enrolled in this study
? To assess the pharmacodynamics in all children/adolescents enrolled in this study, as measured by blood B-cell count
? To evaluate the immune response to ocrelizumab;Primary end point(s): 1. Protocol-defined annualized relapse rate (ARR) (non-inferiority);Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years (ICTRP)

Secondary end point(s): 1. Number of new or enlarging T2 lesions as detected by brain MRI during the double-blind period
2. Number of new or enlarging T2 lesions by Week 96 (non-inferiority)
3. Protocol-defined ARR by Week 96 (non-inferiority)
4. Number of T1 gadolinium (Gd) lesions at Week 12
5. Protocol-defined ARR during the double-blind period (superiority)
6. 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)
7. Change from baseline in targeted vital signs and clinical significant abnormalities in electrocardiogram (ECG) parameters
8. Change from baseline in targeted clinical laboratory test results
9. Concentrations of ocrelizumab at indicated time points
10. Levels of CD19 B-cell count in blood
11. Prevalence of anti-drug antibodies (ADAs) against ocrelizumab at baseline
12. Incidence of ADAs against ocrelizumab during the study;Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years
2-3. At Week 96
4. At Week 12
5. Up to approximately 2 years
6. Up to 48 weeks from the date of last infusion of ocrelizumab
7-8. Baseline to 48 weeks from the date of last infusion of ocrelizumab
9. Weeks 1, 2, 12, 24, 36, 48, 60, 72, 84 and 96
10. Baseline to 48 weeks from the date of last infusion of ocrelizumab
11. At Baseline (Week -8 to -1)
12. Weeks 1, 24, 48, 72, 96; OLE Period: Day 1 of Dose 1 and of all doses afterword?s; Safety Follow up: 12, 36, 60, 84, 108, 132 weeks from the date of last infusion of ocrelizumab (ICTRP)

Registrierungsdatum
01.09.2022 (ICTRP)

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Trial Information Support Line-TISL, global.rochegenentechtrials@roche.com, F. Hoffmann-La Roche Ltd (ICTRP)

Sekundäre IDs
WN42086, 2020-004128-41-HU (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004128-41 (ICTRP)