Operetta 2: A Study To Evaluate Safety And Efficacy Of Ocrelizumab In Comparison With Fingolimod In Children And Adolescents With Relapsing-Remitting Multiple Sclerosis

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05123703

Collaborator

PPD (Industry)

233

Enrollment

Locations

Arms

Anticipated Duration (Months)

6.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This double-blind, double-dummy study will evaluate the safety and efficacy of ocrelizumab compared with fingolimod in children and adolescents with relapsing-remitting multiple sclerosis aged between 10 and < 18 years over a duration of at least 96 weeks.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: Ocrelizumab Other: Ocrelizumab Placebo Drug: Fingolimod Other: Fingolimod Placebo	Phase 3

Detailed Description

This Phase III randomized, double-blind, double-dummy, multicenter study will evaluate the safety and efficacy of ocrelizumab administered by IV infusion every 24 weeks compared with fingolimod taken orally daily, in children and adolescents with Multiple Sclerosis aged between 10 and < 18 years. The study plans to enroll 233 patients in a 1:1 randomization (ocrelizumab:fingolimod), globally. This study consists of a double-blind, double dummy period in which patients will be treated with either active ocrelizumab or active fingolimod for at least 96 weeks. Patients who complete the double-blind period will be offered the possibility to enter an optional open-label extension treatment period of at least 144 weeks with ocrelizumab.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

233 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 4, 2022

Anticipated Primary Completion Date :

Jul 7, 2025

Anticipated Study Completion Date :

Nov 5, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ocrelizumab Participants will receive Ocrelizumab by IV infusion every 24 weeks. The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15 and subsequent doses are given as single infusions of ocrelizumab every 24 weeks. Participants will also receive a placebo of fingolimod (administered as QD capsule).	Drug: Ocrelizumab Ocrelizumab will be administered at a dose of 600 mg by IV infusion on Day 1 and Day 15 (half the dose, 2 weeks apart) and every 24 weeks thereafter. Other: Fingolimod Placebo Fingolimod placebo will be administsred daily as a capsule.
Active Comparator: Fingolimod Participants will receive Fingolimod PO QD as per the prescribing information provided with fingolimod. Patients will also receive a placebo of ocrelizumab (administered as IV infusions on Days 1 and 15, and every 24 weeks thereafter).	Other: Ocrelizumab Placebo Ocrelizumab placebo will be administered by IV infusion on day 1 and Day 15 and every 24 weeks thereafter. Drug: Fingolimod Fingolimod will be administered daily as 0.5 mg capsule.

Arm

Intervention/Treatment

Experimental: Ocrelizumab

Participants will receive Ocrelizumab by IV infusion every 24 weeks. The first dose is given as dual infusions of half the dose of ocrelizumab on Days 1 and 15 and subsequent doses are given as single infusions of ocrelizumab every 24 weeks. Participants will also receive a placebo of fingolimod (administered as QD capsule).

Drug: Ocrelizumab

Ocrelizumab will be administered at a dose of 600 mg by IV infusion on Day 1 and Day 15 (half the dose, 2 weeks apart) and every 24 weeks thereafter.

Other: Fingolimod Placebo

Fingolimod placebo will be administsred daily as a capsule.

Active Comparator: Fingolimod

Participants will receive Fingolimod PO QD as per the prescribing information provided with fingolimod. Patients will also receive a placebo of ocrelizumab (administered as IV infusions on Days 1 and 15, and every 24 weeks thereafter).

Other: Ocrelizumab Placebo

Ocrelizumab placebo will be administered by IV infusion on day 1 and Day 15 and every 24 weeks thereafter.

Drug: Fingolimod

Fingolimod will be administered daily as 0.5 mg capsule.

Outcome Measures

Primary Outcome Measures

Annualized relapse rate (ARR) [Baseline up to approximately 4 years]

Secondary Outcome Measures

Number of new or enlarging T2-hyperintense lesions (T2 lesions) as detected by brain MRI during the double-blind period [Baseline up to approximately 4 years]
Number of new or enlarging T2 lesions by Week 96 [Baseline up to Week 96]
Annualized relapse rate (ARR) by Week 96 [Baseline up to Week 96]
Number of T1 Gd lesions at Week 12 [Week 12]
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) [Baseline up to approximately 8 years]
Prevalence of ADAs at baseline and incidence of ADAs during the study [Baseline up to approximately 8 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Body weight ≥ 50 kg
Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, Version 2012, or McDonald criteria 2017
EDSS at screening: 0-5.5, inclusive
Neurologic stability for ≥ 30 days prior to screening, and between screening and Day 1
At least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of at least one Gd enhancing lesion on MRI within 6 months

Exclusion Criteria:

Known presence or suspicion of other neurologic disorders that may mimic MS
Significant uncontrolled somatic diseases, known active infection or any other significant condition that may preclude patient from participating in the study
Patient with severe cardiac disease or significant findings on the screening ECG

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC San Diego; ACTRI	La Jolla	California	United States	92037
2	University of Colorado Denver Childrens Hospital Rocky Mountain MS Center	Aurora	Colorado	United States	80045
3	Pediatric Multiple Sclerosis and Related Disorders Program at Boston Children's Hospital	Boston	Massachusetts	United States	02115
4	NYU Langone Medical Center; Laura and Isaac Perlmutter Cancer Center	New York	New York	United States	10016
5	The Boster Center for MS	Columbus	Ohio	United States	43235
6	Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY	San Miguel		Argentina	T4000AXL
7	Royal Children's Hospital Melbourne - PIN	Parkville	Victoria	Australia	03052
8	Medizinische Universität Wien; Univ.Klinik fuer Neurologie	Wien		Austria	1090
9	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
10	UZ Gent	Gent		Belgium	9000
11	Multiprofile Hospital For Active Treatment In Neurology And Psychiatry (MHATNP) ''St. Naum"	Sofia		Bulgaria	1797
12	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
13	Centre Hospitalier Universitaire de Bicêtre	Le Kremlin-bicêtre		France	94275
14	Hopital Pierre Wertheimer - Hopital Neurologique; Service de neurologie	Lyon		France	69394
15	CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie	Montpellier		France	34295
16	Vestische Kinder- und Jugendklinik Datteln	Datteln		Germany	45711
17	Attikon University General Hospital	Ahens		Greece	124 64
18	Agios Loucas Clinic SA	Panorama		Greece	552 36
19	Hippokration General Hospital; First Department of Pediatrics	Thessaloniki		Greece	546 42
20	Hospital Eginition; First Department of Neurology	Αθηνα		Greece	115 28
21	Debreceni Egyetem Klinikai Központ; Gyermekklinika	Debrecen		Hungary	4032
22	A.O. Sant'Andrea; UOC Neurologia, Dip. di Neuroscienze, Salute Mentale e Organi di Senso (NESMOS)	Roma	Lazio	Italy	00189
23	Irccs A.O.U.San Martino Ist; Dinogmi	Genova	Liguria	Italy	16132
24	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia	Italy	20132
25	Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele	Catania	Sicilia	Italy	95123
26	Centro para el Desarrollo de la Medicina y de Asistencia	Culiacán Rosales	Sinaloa	Mexico	80230
27	Instytut Centrum Zdrowia Matki Polki; Klinika Neurologii	Łódź		Poland	93-338
28	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona	Spain	08950
29	Hospital de Cruces; Servicio de Neurologia	Barakaldo	Vizcaya	Spain	48903
30	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
31	Hospital Regional Universitario Carlos Haya; Servicio de Neurologia	Malaga		Spain	29010
32	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla		Spain	41009
33	State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine	Kharkiv	Kharkiv Governorate	Ukraine	61068
34	Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital	Lviv	Kharkiv Governorate	Ukraine	79010
35	KZ "Dnipropetrovska oblasna dytiacha klinichna likarnia" DOR	Dnipropetrovsk	Tavria Okruha	Ukraine	49100
36	Great Ormond Street Hospital For Children; Neurology	London		United Kingdom	WC1N 3JH