Long-Term Outcomes and Durability of Effect Following Treatment With Cladribine Tablets for MS (CLASSIC-MS)

Multiple Sclerosis (MS) Clinical Trial

Official title:

Evaluating the Long-Term Outcomes and Durability of Effect Following Treatment With Cladribine Tablets for MS: An Exploratory Phase IV Ambispective Study of Patients Who Previously Participated in the CLARITY/CLARITY-EXT and ORACLE MS Clinical Trials (CLASSIC-MS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03961204
• Other study ID #: MS700568_0026
• Secondary ID: 2019-000069-19
• Status: Completed
• Phase: Phase 4
• Start date: August 15, 2019
• Est. completion date: May 13, 2021

Study information

• Verified date: October 2023
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study was to collect data both retrospectively and prospectively in order to evaluate the long-term outcomes, durability of effect, and real-world treatment patterns following treatment with Cladribine Tablets or placebo in participants with multiple sclerosis (MS) who were previously participated in the parent studies (ORACLE MS and CLARITY/CLARITY-EXT).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 662
• Est. completion date: May 13, 2021
• Est. primary completion date: February 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Participants with relapsing remitting multiple sclerosis (RRMS) randomised in CLARITY/CLARITY-EXT clinical trial(s) who have received greater than or equal to (>=) 1 course of in investigational medicinal product (IMP) Cladribine Tablets or placebo
• Participants with their first clinical demyelinating event randomised in ORACLE MS clinical trial who have received >= 1 course of IMP Cladribine Tablets or placebo
• Participants who has sign informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and this protocol

Exclusion Criteria:

• Participants who has any uncontrolled disease state other than MS, that in the Investigator's opinion, constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
• For study participants at selected sites where MRI assessment will be conducted

following exclusion criteria will apply to MRI assessments only:

• Female study participants who are pregnant
• Participants who are taking Cladribine Tablets as part of another study at the time of the start of this study

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Intervention

Other:
• Data Collection
No study treatment was administered as part of this study

Locations

Country	Name	City	State
Australia	University of Sydney	Camperdown
Austria	Barmherzige Brueder Konventspital Linz - Abteilung fuer Neurologie	Linz
Belgium	Limburgs Universitair Centrum	Hasselt
Belgium	University Hospital of Liege	Seraing
Bulgaria	Military Medical Academy - MHAT - Pleven	Pleven
Bulgaria	MHAT - Shumen, AD	Shumen
Bulgaria	MHAT - "National Heart Hospital" EAD - Multiple Clinics	Sofia
Bulgaria	University Hospital "Saint Naum"	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment - Stara Zagora	Stara Zagora
Canada	Burnaby Hospital Vancouver	Burnaby
Canada	Clinique Neuro-Outaouais	Gatineau
Canada	Recherche Sepmus, Inc.	Greenfield Park
Canada	The Ottawa Hospital - General Campus	Ottawa
Croatia	Clinical Hospital Centar Split	Split
Croatia	General Hospital Varazdin	Varaždin
Czechia	Privatni ordinace - neurologie - Nestatni zdravotnicke zarizeni	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc - Neurologicka klinika	Olomouc
Czechia	Fakultni nemocnice Ostrava - Dept of Neurology	Ostrava-Poruba
Czechia	Vseobecna fakultni nemocnice v Praze - Dept of Neurologicka klinika 1.LF UK a VFN v Praze	Praha 2
Czechia	Fakultni nemocnice v Motole - Interní klinika 2. LF UK a FN Motol	Praha 5
Czechia	Krajska zdravotni, a.s. - Nemocnice Teplice, o.z. - Neurologicke oddeleni	Teplice
Estonia	Astra Team Clinic	Tallinn
Estonia	Tartu University Hospital	Tartu
Finland	Neuro NEO Oy - NEO Research	Turku
France	Hopital Roger Salengro - CHU Lille - service de neurologie D	Lille
France	CHU de Nîmes - Hôpital Carémeau - Service de Neurologie	Nimes
France	CHU Rennes - Hopital Pontchaillou - Neurologie - Clinique Neurologique	Rennes cedex 09
Georgia	Ltd. Pineo Medical Ecosystem	Tbilisi
Georgia	S. Khechinashvili University Clinic	Tbilisi
Germany	Heinrich-Heine-Universitaet Duesseldorf - Klinik fuer Nephrologie	Duesseldorf
Germany	Diakoniekrankenhaus Henriettenstiftung GgmBH	Hanover
Germany	Klinik Und Poliklinik Fur Neurologie	Regensburg
Germany	Universitaetsmedizin Rostock - Klinik und Poliklinik fuer Neurologie	Rostock
Italy	Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari - Neurofisiopatologia	Bari
Italy	A.O.U. Policlinico V. Emanuele - Presidio Gaspare Rodolico - Clinica Neurologica I	Catania
Italy	Ospedale Clinicizzato SS. Annunziata - Centro Regionale Sclerosi Multipla	Chieti
Italy	Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)	Gallarate
Italy	Azienda Ospadaliero Universitaria San Martino - PARENT	Genova
Italy	Ospedale San Raffaele - U.O. di Neurologia	Milano
Italy	Azienda Ospedaliera Universitaria "Federico II" - Gastroenterologia Pediatrica	Napoli
Italy	Azienda Ospedaliero_Universitaria S. Luigi Gonzaga - Centro di Riferimento Regionale Sclerosi Multipla	Orbassano
Italy	Fondazione Istituto Neurologico Casimiro Mondino - Unità Complessa Malattie Cerebrovascolari/Stroke U	Pavia
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata - Dip. Neuroscienze-Centro per la Sclerosi Multipla	Roma
Italy	Ospedale Sant'Andrea di Roma - MS Center	Rome
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Lebanon	American University of Beirut Medical Center	Beirut
Lebanon	Bellevue Medical Center	Beirut
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics - Neurology Clinic	Kaunas
Norway	Department of Neurology, Haukeland University	Haukeland
Norway	St Olavs Hospital - PARENT	Trondheim
Poland	Szpital im. Mikolaja Kopernika - Neurology	Gdansk
Poland	Uniwersyteckie Centrum Kliniczne - Dept of Neurology	Gdansk
Poland	Prof. Dr. med. Zbigniew Stelmasiak Specjalistyczny Gabinet Neurologiczny	Lublin
Poland	Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu - Dept of Neurology	Poznan
Poland	Instytut Psychiatrii i Neurologii	Warszawa
Portugal	Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos - Serviço de Neurologia	Lisboa
Romania	SC Sana Monitoring SRL.	Bucaresti
Romania	Spitalul Clinic Judetean de Urgenta Targu Mures - Sectia Clinica Neurologie I	Targu Mures
Romania	Spitalul Clinic Judetean de Urgenta "Pius Branzeu" Timisoara - Clinica de Neurologie II	Timisoara
Russian Federation	SAIH "Kemerovo Regional Clinical Hospital" - PARENT	Kemerovo
Russian Federation	BMI "Kursk Regional Clinical Hospital"	Kursk
Russian Federation	NHI "Central Clinical Hospital #2 of JSC "Russian Railways" n.a. N.A. Semashko	Moscow
Russian Federation	SBIH of Moscow "City Clinical Hospital # 24" - Branch 1	Moscow
Russian Federation	SBIH of Moscow region " Moscow Regional Scientific and Research Clinical Institute n.a. M.F. Vladimi	Moscow
Russian Federation	Medis	Nizhny Novgorod
Russian Federation	RSHI"State Novosibirsk Regional Clinical Hospital"	Novosibirsk
Russian Federation	SEIHPE "Rostov State Medical University of MoH of RF"	Rostov-on-don
Russian Federation	LLC " International Clinic MEDEM"	Saint-Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University - PARENT	Saint-Petersburg
Russian Federation	SBIH "Leningrad Regional Clinical Hospital"	Saint-Petersburg
Russian Federation	SBIH "Samara Regional Clinical Hospital n.a. V.D. Seredavin	Samara
Russian Federation	SBEI HPE "Saratov State Medical University n.a. V. I. Razumovskiy" of the MoH of the RF	Saratov
Russian Federation	RSBIH "Smolensk Regional Clinical Hospital"	Smolensk
Russian Federation	Saint-Petersburg SU on b.o. City Multifield Hospital #2 - Intensive Pulmonology and Thoracal Surgery	St. Petersburg
Russian Federation	Siberian State Medical University	Tomsk
Russian Federation	Regional Multiple Sclerosis Centre b/o CC ECM "Neftyanik" - Neurology	Tyumen
Russian Federation	SBHI of Yaroslavl Region "Clinical Hospital # 8" - Cardiology	Yaroslavl
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Center Nis - Clinic of Neurology	Nis
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital Universitario Nuestra Señora de la Candelaria - Servicio de Neurologia	Santa Cruz de Tenerife
Sweden	Sahlgrenska Sjukhuset	Göteborg
Switzerland	(CHUV), Centre Hospitalier Universitaire Vaudois - Departement des Neurosciences Cliniques	Lausanne
Tunisia	Hôpital Fattouma Bourghiba	Monastir
Tunisia	Hôpital Habib Bourguiba - Service de Neurologie	Sfax
Tunisia	Hopital Militaire de Tunis	Tunis
Ukraine	SI Institute of Neurology, Psychiatry and Narcology of NAMSU - Dept of Neuroinfections and Multiple Sclerosis	Kharkiv
Ukraine	Vinnitsa State Medical University - Neurology dept	Vinnytsia
United Kingdom	Nottingham University Hospital - Division of Clinical Neurology	Nottingham
United Kingdom	Royal Hallamshire Hospital - Dept of Neurology	Sheffield
United States	MS Center of Atlanta	Atlanta	Georgia
United States	University of Maryland, Baltimore - Maryland Center for MS	Baltimore	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Sanford Neuro Health Center - Neurology	Fargo	North Dakota
United States	Empire Neurology, PC - Empire Neurology PC	Latham	New York
United States	OMRF	Oklahoma City	Oklahoma
United States	Rowan University School of Osteopathic Medicine - Department of Medicine	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  Estonia,  Finland,  France,  Georgia,  Germany,  Italy,  Korea, Republic of,  Lebanon,  Lithuania,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Spain,  Sweden,  Switzerland,  Tunisia,  Ukraine,  United Kingdom, 

References & Publications (1)

Giovannoni G, Boyko A, Correale J, Edan G, Freedman MS, Montalban X, Rammohan K, Stefoski D, Yamout B, Leist T, Aydemir A, Borsi L, Verdun di Cantogno E. Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Using Wheelchair or Being Bedridden Assessed by Expanded Disability Status Scale (EDSS) Score 7.0 or Higher	EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. EDDS is a scale from 0-10 that evaluates a person with Multiple Sclerosis (MS) disability/neurologic function level where 0=normal and 10=death due to MS. Score of 7.0 is defined as unable to walk beyond approximately 5 meters even with aid, essentially restricted to wheelchair; wheels self in standard wheelchair and transfers alone; up and about in wheelchair some 12 hours a day. Score of 8.0 is defined as Essentially restricted to bed or chair or perambulated in wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms.	3 months prior to study visit 1. Retrospectively from end of parent study (NCT00213135, NCT00641537 and NCT00725985) to study visit 1 (study visit 1 occurred up to 3 months from screening)
Secondary	Percentage of Participants With Expanded Disability Status Scale (EDSS) Score 6.0 or Higher	EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. EDDS is a scale from 0-10 that evaluates a person with MS disability/neurologic function level where 0= normal and 10= death due to MS. Score of 6.0 is defined as "intermittent or unilateral constant assistance (cane, crutch and brace) required to walk about 100 meters with or without resting".	At study visit 1. Retrospectively after last IMP administration from parent study (NCT00213135, NCT00641537 and NCT00725985) to study visit 1 (study visit 1 occurred up to 3 months from screening)
Secondary	Clinical and Demographic Characteristic: Age, Disease Duration	Clinical and demographic characteristics including age and disease duration is reported in the form of long term responders and non-responder. Here long term responder is defined as study participants not requiring disease modifying drug (DMD) 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	Number of Participants in Each Category of Clinical and Demographic Characteristics	Clinical and demographic characteristics included gender, race, disease classification (relapsing remitting multiple sclerosis [RRMS], Secondary Progressive Multiple Sclerosis [SPMS], unknown & no MS disease), Prior use of DMDs & high-disease activity (HAD) status, education level and employment status. Number of participants in each category of clinical and demographic characteristics were reported in form of long term responders & non-responder. Here long term responder is defined as participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD < 4 years following their last dose of IMP in parent study.	At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	Clinical Characteristic: Expanded Disability Status Scale (EDSS) Score	EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory & cerebral functions, as well as walking ability. EDSS scores range from 0.0 (normal) to 10.0 (dead). Clinical characteristics of EDSS score in form of long-term responders & non-responder was reported for at parent study baseline (based on retrospective data collection [based on chart review] at study visit 1) & study visit 1. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD < 4 years following their last dose of IMP in parent study.	At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	Clinical Characteristic: Number of Relapses	Relapse was defined as participant-reported symptoms & objectively observed signs typical of an acute inflammatory demyelinating event in CNS, developing acutely or sub-acutely with duration of at least 24 hours, in absence of fever or infection. Clinical characteristics of number of relapses during last year before enrollment of parent study (it is reported based on retrospective data collection [based on chart review] at study visit 1) in the form of long-term responders & non-responder was reported. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 1, occurred up to 3 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	Number of Total T1-weighted (T1-W) Lesions	Total number of T1-W lesion were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	Number of Total T2-weighted (T2-W) Lesions	Total number of T2-W lesion were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	T1-weighted (T1-W) Lesion Volume	T1-W lesion volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	T2-weighted (T2-W) Lesion Volume	T2-W lesion volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)
Secondary	Total Brain Volume	Brain volume were measured by Using magnetic resonance imaging (MRI) Scans. Here long term responder is defined as study participants not requiring DMD 4 years or later following their last dose of IMP in parent study. Non-responder is defined as study participants requiring DMD less than 4 years following their last dose of IMP in parent study.	At study visit 2, within 6 months from screening (Retrospective analysis of medical record of parent study-NCT00213135, NCT00641537 and NCT00725985)

External Links

•   Trial Awareness and Transparency website
•   US Medical Information website, Medical Resources