Clinical trial NCT03589105: A Study to Provide Complementary Efficacy, Safety and Patient Reported Outcomes Data in Participants With Active Relapsing Forms of Multiple Sclerosis (MS) in a Pragmatic Setting
Official title: An Open-Label, Single-Arm Phase IV Study To Assess Ocrelizumab Efficacy, Safety, And Impact On Patient Reported Outcomes (PROS) In Patients With Active Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-07-17
Enrollment: 423
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This national, open-label study is designed to give complementary efficacy, safety and patient reported outcomes (PROs) data in participants with active relapsing forms of MS. Participants will receive a maximum of 2 treatment cycles of ocrelizumab infusions: an initial dose of two 300 milligram (mg) infusions separated by 14 days followed by one single infusion of 600 mg ocrelizumab 24 weeks after the first infusion. Disease activity is determined by clinical relapses and/or Magnetic Resonance Imaging (MRI) activity.


Eligibility criteria: Inclusion Criteria:

* Age \>/=18 years at screening
* Patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features: (i) at least one clinical relapse over a 6-month period prior to screening; (ii) AND/OR at least one T1 gadolinium-enhancing lesion or new and/or enlarging T2 lesion as detected by brain Magnetic Resonance Imaging (MRI) performed over a 3 months period prior to screening with no change of Disease-Modifying Treatment(s) (DMT) compared to a previous MRI performed within 24 months before screening
* For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 12 months after the last dose of ocrelizumab
* Participants should be beneficiary of healthcare coverage under the social security system

Exclusion Criteria:

* Diagnosis of primary progressive MS
* Inability to complete an MRI (contraindications for MRI include but are not restricted to weight ≥140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc...)
* Gadolinium intolerance
* History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord
* History or known presence of central nervous system (CNS) or spinal cord tumor (e.g., meningioma, glioma)
* History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency)
* History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1 (HTLV-1), herpes zoster myelopathy)
* History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis; MELAS \[mitochondrial myopathy, encephalopathy, lactic acidosis, stroke\] syndrome)
* Neuromyelitis optica
* History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjogren's syndrome, Behçet's disease, sarcoidosis)
* History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression)
* Vulnerable patients (Patient referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-1-2 of the French Public Health Code)

Primary outcomes:
measure: Percentage of participants free of disease activity
timeFrame: From Enrollment to Week 48
Secondary outcomes:
measure: Annualized relapse rate
timeFrame: At Week 48
measure: Percentage of participants with stable, improved, or worsened expanded disability status scale (EDSS)
timeFrame: From Enrollment to Week 48
measure: Percentage of participants with confirmed disability progression at Week 24 (CDP24)
timeFrame: At Week 48
measure: Mean Change in EDSS
timeFrame: From Baseline to Week 48
measure: Percentage of relapse-free RMS participants
timeFrame: From Enrollment to Week 24 and Week 48
measure: Percentage of participants with no T1 gadolinium-enhancing lesion and no new and/or enlarging T2 lesion as detected by brain MRI
timeFrame: At Week 48
measure: Percentage of participants with no T1 gadolinium-enhancing lesion as detected by brain MRI
timeFrame: At Week 48
measure: Percentage of participants with no new and/or enlarging T2 lesion as detected by brain MRI
timeFrame: At Week 48
measure: Change in the score of MS symptom severity scale (SymptoMScreen)
timeFrame: At Week 24 and Week 48
measure: Change in the score of Modified Fatigue Impact Scale (MFIS)
timeFrame: At Week 24 and Week 48
measure: Change in the score of EuroQol 5-Dimension Questionnaire (EQ-5D-5L with Visual Analogue Scale (VAS)) for health-related quality of life
timeFrame: At Week 24 and Week 48
measure: Change in the score of Work Productivity and Activity Impairment scale (WPAI:SHP)
timeFrame: At Week 24 and Week 48
measure: Change in the score of Multiple Sclerosis International Quality Of Life Questionnaire (MusiQOL)
timeFrame: At Week 24 and Week 48
measure: Change in the score of Treatment Satisfaction Questionnaire for Medication (TSQM-14)
timeFrame: At Week 24 and Week 48
measure: Percentage of Participants with Adverse Events (AE)
timeFrame: From Baseline to Week 48
Other outcomes:
Locations:
city: Agen
country: France
facility: Centre hospitalier d'Agen; Neurologie
city: Amiens Cedex1
country: France
facility: CHU Amiens Hopital Sud; Neurologie
city: Angers Cedex 9
country: France
facility: CHU Angers, Batiement Larrey 2, Neurologie
city: Besançon
country: France
facility: CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin; Service de neurochirurgie B
city: Brest
country: France
facility: CHU Brest Hopital La Cavale Blanche; Neurologie
city: Bron
country: France
facility: Hopital Pierre Wertheimer; Neurologie D
city: Caen
country: France
facility: Hopital Cote De Nacre; Unite Neurologie Generale
city: Cahors
country: France
facility: CH Jean Rougier; Neurologie
city: Calais Cedex
country: France
facility: Ch De Calais; Hopital De Jour
city: CHAMBERY Cedex
country: France
facility: CHMS Site Chambery; Neurologie
city: Clermont Ferrand
country: France
facility: CHU Hopital Gabriel Montpied; Service de Neurologie
city: Dijon Cedex
country: France
facility: Hôpital General - Service de neurologie; Service de neurologie
city: Gonesse
country: France
facility: CH de Gonesse; Neurologie
city: La Tronche
country: France
facility: CHU de Grenoble; Neurologie
city: Le Chesnay Cedex
country: France
facility: Centre hospitalier Andre Mignot; Neurologie
city: Le Mans
country: France
facility: CH Le Mans; Neurologie
city: Libourne Cedex
country: France
facility: Centre hospitalier de Libourne Hopital Robert Boulin; Neurologie
city: Lille
country: France
facility: CH St Vincent de Paul
city: Lille
country: France
facility: Hopital Roger Salengro; Service de Neurologie
city: Limoges
country: France
facility: CHU Dupruytren - Limoges; Neurologie
city: Marseille
country: France
facility: Hopital européen de Marseille; Neurologie
city: Marseille
country: France
facility: CHU de la Timone - Hopital d Adultes; Service de Neurologie
city: Marseille
country: France
facility: Fondation Hopital Saint Joseph; Neurologie
city: Meaux
country: France
facility: Gh De Meaux; Neurologie
city: Metz Tessy
country: France
facility: Centre hospitalier Annecy Genevois Site St Julien; Neurologie
city: Montlucon
country: France
facility: Centre hospitalier de Montlucon; Neurologie
city: Montpellier
country: France
facility: Hopital Gui de Chauliac; Neurologie
city: Mulhouse Cedex 1
country: France
facility: Centre hospitalier de Mulhouse Hopital Emile Muller; Neurologie
city: Nancy
country: France
facility: Hopital Central - CHU de Nancy; Service de Neurologie
city: Nantes
country: France
facility: Hôpital Guillaume et René Laënnec; Service Neurologie
city: Nice
country: France
facility: Hôpital Pasteur; Service de Neurologie
city: Nimes
country: France
facility: CHU de Nîmes Hopital Caremeau; Service de Neurologie
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint Joseph; Service de Neurologie et Neurovasculaire
city: Paris
country: France
facility: Fondation Rothschild; Service de Neurologie
city: Paris
country: France
facility: Hopital Saint Antoine; Neurologie
city: Poitiers
country: France
facility: CHU Poitiers - La Milétrie; Neurologie
city: Quimper
country: France
facility: Centre Hospitalier de Cornouaille; Neurologie
city: Rennes
country: France
facility: Hopital Pontchaillou
city: Rouen
country: France
facility: Hôpital Charles Nicolle; Service de Neurologie
city: Saint-priest-en-jarez
country: France
facility: CHU Saint Etienne - Hôpital Nord; Neurologie
city: Strasbourg
country: France
facility: Hopital Civil de Strasbourg; Service de Neurologie
city: Suresnes
country: France
facility: Hopital Foch; Neurologie
city: Toulon
country: France
facility: HIA de Toulon hôpital militaire; Neurologie
city: Tourcoing Cedex
country: France
facility: Centre hospitalier Guy Chatiliez de Tourcoing; Neurologie
city: Valence Cedex 9
country: France
facility: Centre hospitalier de Valence; Neurologie
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Manchon E, Laplaud D, Vukusic S, Labauge P, Moreau T, Kobelt G, Grouin JM, Lotz M, Pau D, Christine LF. Efficacy, safety and patient reported outcomes in patients with active relapsing multiple sclerosis treated with ocrelizumab: Final results from the PRO-MSACTIVE study. Mult Scler Relat Disord. 2022 Dec;68:104109. doi: 10.1016/j.msard.2022.104109. Epub 2022 Aug 13.