Prospective Effectiveness and Safety Study of Cladribine in Participants Who Change First-line DMD Treatments for Multiple Sclerosis (CLAD CROSS)

NCT04934800 | Completed Results

• 1 other identifier: MS700568_0070
• Study Type: observational
• Target: 256
• Locations: 7 countries
• Sites: 61

Brief Summary

The main aim was to study in the real world setting the effectiveness of Cladribine tablets in terms of Annualized Relapse Rate (ARR) and disability progression, in participants who switched from a first line Disease Modifying Drug (DMD) (Interferons, Glatiramer Acetate, Teriflunomide, (Dymethyl fumarate) \[DMF\]) to treatment with Cladribine tablets in routine clinical practice.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Cladribine; MAVENCLAD ®

Outcome Measures

Primary Outcomes (1)

• Change in Annualized Relapse Rate (ARR) Between the Pre-Baseline 12-Month Period (Baseline) and Over the 12 Months Period Before the End of Study Follow-Up (2 Years)

  ARR defined as the number of relapses per year. A relapse was defined as the appearance of new symptoms or the exacerbation of pre-existing symptoms that were attributed to Multiple Sclerosis (MS) and occurred over a minimum of 24 hours and separated from a previous attack by at least 30 days, in the absence of fever or infection. Baseline ARR was defined as the total number of relapses reported in the last 12 months prior to Cladribine treatment. ARR 12-months prior to End Of Study was calculated as the sum of the number of MS relapses reported at Visit 3 and Visit 4 divided by the number of days between Visit 4 date and Visit 2 date and multiplied by 365.25. For a change from baseline, 95 percent (%) Confidence Interval (CI) for the difference were presented together with summary statistics. These CIs were included as a descriptive measure of effect.

  12-months pre-baseline (Baseline) and 12 Months Prior to End of Study follow up (2 years)

Secondary Outcomes (10)

• Change in ARR Between the Pre-Baseline 12-Month Period (Baseline) and Over the 12 Months Period After the Start of Cladribine (1 Year)

  12-month pre-baseline period (baseline) and over the 12 months period after start of Cladribine treatment (1 year)

• Percentage of Participants With 6-Month Disability Progression Measured With Expanded Disability Status Scale (EDSS)

  At EOS (24 months follow-up)

• Percentage of Participants With Overall 6-Month Disability Progression Measured With EDSS, Timed 25 Foot Walk (T25FW) or 9 Hole Peg Test (9HPT)

  At EOS (24 months follow-up)

• Percentage of Participants With 6-Month Disability Improvement Measured With EDSS

  At EOS (24 months follow-up)

• Percentage of Participants With Overall 6-Month Disability Improvement Measured With EDSS, Timed 25 Foot Walk (T25FW) or 9 Hole Peg Test(9HPT)

  At EOS (24 months follow-up)

Study Arms (1)

Cladribine

Drug: Cladribine

Interventions

Cladribine DRUG

No intervention will be administered as a part of this study. Participants who had switched from first-line DMD treatments to treatment with cladribine tablets in routine clinical practice will be assessed for 2 years in this study.

Also known as: MAVENCLAD ®

Cladribine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants with a confirmed diagnosis of Highly Active Relapsing-Remitting Multiple Sclerosis (RRMS).

You may qualify if:

• Participants with confirmed diagnosis of RRMS diagnosed by the treating physician according to applicable clinical practice guidelines -(currently McDonald 2017 criteria), with high disease activity
• Participants should have been treated with the same first-line DMD (Interferons, Glatiramer Acetate, Teriflunomide, DMF) and at a stable dose for at least one year prior to switch to Cladribine tablets and should have been prescribed Cladribine tablets, according to the decision of the treating physician, prior to enrollment in the study. Any washout period and/or washout methods required before switching (such as elimination of Teriflunomide) must have been conducted, according to the decision of the treating physician
• Required history data should be available: Multiple Sclerosis (MS) data for the 12-months pre-baseline period (annualized relapse rate); MS Medication History (prior DMDs)
• Fulfilment of the criteria for treatment with Cladribine tablets per standard of care in accordance with the local Summary of Product Characteristics (SmPC)

You may not qualify if:

• Contraindications to use of cladribine tablets according to the SmPC
• Participants with history of alcohol or drug abuse that could potentially interfere with their participation in the study
• Participants that have received Cladribine in the past
• Concurrent participation in an investigational study in which participant assessment and/or treatment may be dictated by a protocol

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead
• Merck Hellas sa., Greece, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (61)

KH der Barmherzige Brüder Eisenstadt - Neurology

Eisenstadt, Austria

Location

Dr. Reinhard Krendl-Head

Sankt Veit an der Glan, Austria

Location

Klinik Florisdorf

Vienna, Austria

Location

University of Thrace, Medical School - Neurology Department

Alexandroupoli, Greece

Location

251 General Air Force Hospital

Athens, Greece

Location

417 NIMITS Hospital

Athens, Greece

Location

Aeginiteion Hospital, University of Athens - A' Neurology Department

Athens, Greece

Location

Attikon University Hospital

Athens, Greece

Location

Evangelismos Hospital - Neurology Department

Athens, Greece

Location

Genaral Hospital of Elefsina "Thriasio"

Athens, Greece

Location

General Hospital of Athens "Evangelismos"

Athens, Greece

Location

University of Ioannina - Neurology Department, Ioannina

Ioannina, Greece

Location

University General Hospital of Larissa - Rheumatology Clinic

Larissa, Greece

Location

Iatriko Palaioy Faliroy, Medical Center - Neurology Department

Palaió Fáliro, Greece

Location

General Hospital of Patra "Agios Andreas"

Pátrai, Greece

Location

University General Hospital of Patra

Pátrai, Greece

Location

AHEPA General Hospital of Thessaloniki

Thessaloniki, Greece

Location

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, Greece

Location

Interbalkan Hospital of Thessaloniki

Thessaloniki, Greece

Location

Papageorgiou General Hospital Thessaloniki

Thessaloniki, Greece

Location

St Luke's Hospital

Thessaloniki, Greece

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII) - Dipartimento di Neurologia

Bergamo, Italy

Location

Fondazione Istituto G.Giglio di Cefalù - Neurologia-Centro Sclerosi Multipla

Cefalù, Italy

Location

Università degli Studi G. D'Annunzio

Chieti, Italy

Location

Azienda Ospedaliera Universitaria Arcispedale Sant'Anna - Neurologia

Cona, Italy

Location

Ospedali Riuniti di Foggia - Neurology

Foggia, Italy

Location

Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate) - Neurologia 2 - Sclerosi Multipla

Gallarate, Italy

Location

Ospedale San Luca - S.C.Oncologia

Lucca, Italy

Location

ASL 1 Avezzano L'Aquila Sulmona- Ospedale Regionale San Salvatore - Dipartimento di Neurologia

L’Aquila, Italy

Location

IRCCS Centro Neurolesi Bonino Pulejo - U.O. di Neurofisipatologia ed Ambulatori

Messina, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli - U.O.S. Malattie Degenerative del S.N.C.

Napoli, Italy

Location

Ospedale Maggiore della carità - Novara

Novara, Italy

Location

Centro di Riferimento Regionale per la Sclerosi Multipla (CRESM) - SCDO Neurologia

Orbassano, Italy

Location

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone - Dipartimento di Neuroscienze

Palermo, Italy

Location

Azienda Ospedaliera di Udine Ospedale S. Maria della Misericordia - UO Neurologia

Perugia, Italy

Location

Grande Ospedale Metropolitano "Bianchi Melacrino Morelli - Centro Regionale Epilessia

Reggio Calabria, Italy

Location

Azienda Ospedaliera San Filippo Neri - Neurologia

Roma, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza - Dip. di Neurologia e Psichiatria (servizio EMG)

Roma, Italy

Location

A. O. U. San Giovanni Di Dio e Ruggi D'Aragona - Struttura Complessa di Oculistica

Salerno, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - D.U.Neurologia

Verona, Italy

Location

Vestre Viken HF Drammen Sykehus - former Sykehuset Buskerud

Drammen, Norway

Location

Sykehuset Namsos

Namsos, Norway

Location

Oslo Universitetssykehus HF - Ullevål

Oslo, Norway

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku - Dept of Neurology

Bialystok, Poland

Location

Szpital Specjalistyczny im. L.Rydygiera w Krakowie - Neurology Department

Krakow, Poland

Location

Szpital Uniwersytecki w Krakowie - Uniwersytet Jagiellonski Collegium Medicum

Krakow, Poland

Location

Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu - Dept of Neurology

Poznan, Poland

Location

Pomorski Uniwersytet Medyczny - Klinika Neurologii

Szczecin, Poland

Location

Wojskowy Instytut Medyczny - Klinika Neurologiczna

Warsaw, Poland

Location

SPZOZ Wojewodzki Szpital Specjalistyczny nr 3 w Rybniku

Żory, Poland

Location

Centro Hospitalar de Lisboa Ocidental, E.P.E. - Hospital de Egas Moniz - Serviço de Neurologia

Lisbon, Portugal

Location

Unidade Local de Saúde de Matosinhos, EPE (Hospital Pedro Hispano) - Serviço de Neurologia

Matosinhos Municipality, Portugal

Location

Centro Hospitalar de São João, E.P.E. - Serviço de Neurologia

Porto, Portugal

Location

Hospital Garcia de Orta, EPE - Serviço de Neurologia

Pragal, Portugal

Location

Centro Hospitalar de Setubal, EPE - Hospital São Bernardo

Setúbal, Portugal

Location

Unidade Local de Saúde do Alto Minho, EPE - Serviço de Neurologia

Viana de Castelo, Portugal

Location

Inselspital - Universitaetsspital Bern - Neuropsychologische Rehabilitation, Neurologie

Bern, Switzerland

Location

(CHUV), Centre Hospitalier Universitaire Vaudois - Departement des Neurosciences Cliniques

Lausanne, Switzerland

Location

Luzerner Kantonsspital - Zentrum fuer Neurologie und Neurorehabilitation

Lucerne, Switzerland

Location

Ospedale Regionale di Lugano - Neurologia

Lugano, Switzerland

Location

Hôpital Régional Sion-Hérens-Conthey - Neurologie

Sion, Switzerland

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: June 22, 2021
• Study Start: December 10, 2019
• Primary Completion: May 20, 2024
• Study Completion: May 20, 2024
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Locations

IT (19); NO (3); PT (6); PL (7); AU (3); GR (18); CH (5)