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

Multiple Sclerosis Clinical Trial

— PRO-MSACTIVE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03589105
• Other study ID #: ML40359
• Secondary ID: 2018-000780-91
• Status: Completed
• Phase: Phase 4
• Start date: August 6, 2018
• Est. completion date: February 15, 2021

Study information

• Verified date: January 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 423
• Est. completion date: February 15, 2021
• Est. primary completion date: February 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ocrelizumab 300 mg
Two doses of 300 mg infusion administered 14 days apart.
• Ocrelizumab 600 mg
A single does of 600 mg infusion administered 24 weeks after the initial dose.

Locations

Country	Name	City	State
France	Centre hospitalier d'Agen; Neurologie	Agen
France	CHU Amiens Hopital Sud; Neurologie	Amiens Cedex1
France	CHU Angers, Batiement Larrey 2, Neurologie	Angers Cedex 9
France	CHU de Besancon Hopital Jean Minjoz; Service de Neurologie	Besançon
France	Groupe Hospitalier Pellegrin; Service de neurochirurgie B	Bordeaux
France	CHU Brest Hopital La Cavale Blanche; Neurologie	Brest
France	Hopital Pierre Wertheimer; Neurologie D	Bron
France	Hopital Cote De Nacre; Unite Neurologie Generale	Caen
France	CH Jean Rougier; Neurologie	Cahors
France	Ch De Calais; Hopital De Jour	Calais Cedex
France	CHMS Site Chambery; Neurologie	CHAMBERY Cedex
France	CHU Hopital Gabriel Montpied; Service de Neurologie	Clermont Ferrand
France	Hôpital General - Service de neurologie; Service de neurologie	Dijon Cedex
France	CH de Gonesse; Neurologie	Gonesse
France	CHU de Grenoble; Neurologie	La Tronche
France	Centre hospitalier Andre Mignot; Neurologie	Le Chesnay Cedex
France	CH Le Mans; Neurologie	Le Mans
France	Centre hospitalier de Libourne Hopital Robert Boulin; Neurologie	Libourne Cedex
France	CH St Vincent de Paul	Lille
France	Hopital Roger Salengro; Service de Neurologie	Lille
France	CHU Dupruytren - Limoges; Neurologie	Limoges
France	CHU de la Timone - Hopital d Adultes; Service de Neurologie	Marseille
France	Fondation Hopital Saint Joseph; Neurologie	Marseille
France	Hopital européen de Marseille; Neurologie	Marseille
France	Gh De Meaux; Neurologie	Meaux
France	Centre hospitalier Annecy Genevois Site St Julien; Neurologie	Metz Tessy
France	Centre hospitalier de Montlucon; Neurologie	Montlucon
France	Hopital Gui de Chauliac; Neurologie	Montpellier
France	Centre hospitalier de Mulhouse Hopital Emile Muller; Neurologie	Mulhouse Cedex 1
France	Hopital Central - CHU de Nancy; Service de Neurologie	Nancy
France	Hôpital Guillaume et René Laënnec; Service Neurologie	Nantes
France	Hôpital Pasteur; Service de Neurologie	Nice
France	CHU de Nîmes Hopital Caremeau; Service de Neurologie	Nimes
France	Fondation Rothschild; Service de Neurologie	Paris
France	Groupe Hospitalier Paris Saint Joseph; Service de Neurologie et Neurovasculaire	Paris
France	Hopital Saint Antoine; Neurologie	Paris
France	CHU Poitiers - La Milétrie; Neurologie	Poitiers
France	Centre Hospitalier de Cornouaille; Neurologie	Quimper
France	Hopital Pontchaillou	Rennes
France	Hôpital Charles Nicolle; Service de Neurologie	Rouen
France	CHU Saint Etienne - Hôpital Nord; Neurologie	Saint-priest-en-jarez
France	Hopital Civil de Strasbourg; Service de Neurologie	Strasbourg
France	Hopital Foch; Neurologie	Suresnes
France	HIA de Toulon hôpital militaire; Neurologie	Toulon
France	Centre hospitalier Guy Chatiliez de Tourcoing; Neurologie	Tourcoing Cedex
France	Centre hospitalier de Valence; Neurologie	Valence Cedex 9

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants free of disease activity	This outcome measure evaluates the impact of ocrelizumab on disease activity in participants with active Relapsing Multiple Sclerosis (RMS). Freedom of disease activity is defined as participant without any relapse from enrollment to Week 48 and without T1 Gadolinium-enhancing lesion detected by brain MRI at Week 48 and without any new and/or enlarging T2 lesion detected by brain MRI at Week 48.	From Enrollment to Week 48
Secondary	Annualized relapse rate	Annualized relapse rate is defined as the total number of clinical relapses divided by the number of participant-years of study treatment exposure. This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	At Week 48
Secondary	Percentage of participants with stable, improved, or worsened expanded disability status scale (EDSS)	This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	From Enrollment to Week 48
Secondary	Percentage of participants with confirmed disability progression at Week 24 (CDP24)	This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	At Week 48
Secondary	Mean Change in EDSS	This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	From Baseline to Week 48
Secondary	Percentage of relapse-free RMS participants	This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	From Enrollment to Week 24 and Week 48
Secondary	Percentage of participants with no T1 gadolinium-enhancing lesion and no new and/or enlarging T2 lesion as detected by brain MRI	This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	At Week 48
Secondary	Percentage of participants with no T1 gadolinium-enhancing lesion as detected by brain MRI	This outcome measure describes the efficacy of ocrelizumab in active RMS participants.	At Week 48
Secondary	Percentage of participants with no new and/or enlarging T2 lesion as detected by brain MRI	This outcome measure evaluates the impact of ocrelizumab on disease activity in participants with active RMS.	At Week 48
Secondary	Change in the score of MS symptom severity scale (SymptoMScreen)	This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients.	At Week 24 and Week 48
Secondary	Change in the score of Modified Fatigue Impact Scale (MFIS)	This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients.	At Week 24 and Week 48
Secondary	Change in the score of EuroQol 5-Dimension Questionnaire (EQ-5D-5L with Visual Analogue Scale (VAS)) for health-related quality of life	This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients.	At Week 24 and Week 48
Secondary	Change in the score of Work Productivity and Activity Impairment scale (WPAI:SHP)	This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients.	At Week 24 and Week 48
Secondary	Change in the score of Multiple Sclerosis International Quality Of Life Questionnaire (MusiQOL)	This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients.	At Week 24 and Week 48
Secondary	Change in the score of Treatment Satisfaction Questionnaire for Medication (TSQM-14)	This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients.	At Week 24 and Week 48
Secondary	Percentage of Participants with Adverse Events (AE)	This outcome measure describes ocrelizumab safety in active RMS patients. Severity of AEs is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0)	From Baseline to Week 48