Oral Cladribine in Early Multiple Sclerosis (MS)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Oral Cladribine in Subjects With a First Clinical Event at High Risk of Converting to MS

Sponsors

Lead Sponsor: EMD Serono Research & Development Institute, Inc.

Source EMD Serono
Brief Summary

A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Participants in either the cladribine or placebo group may also enter treatment periods with open-label interferon-beta or open-label cladribine depending upon the disease status. The primary objective of this study is to evaluate the effect of two dosage regimens of oral cladribine versus placebo on the time to conversion to multiple sclerosis (MS) (from randomization) according to the Poser criteria in participants with first clinical demyelinating event at high risk of converting to MS.

Detailed Description

This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of participants who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Participants must have a minimum of 2 clinically silent lesions on the Screening magnetic resonance imaging (MRI). The study will include a pre-study evaluation period (Screening period: between 10 and 28 days prior to the start of treatment with blinded study medication (oral cladribine or placebo). Depending upon the clinical course of their MS, participants will then proceed from the ITP to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU period (with either open-label low-dose cladribine or no additional treatment (if no progression to MS has been noted after the initial treatment period). The single primary endpoint for the overall study, which will be determined during the ITP, is time to conversion to MS (from randomization), according to the Poser criteria. For every participants, eligibility for study enrollment and entry into each of the study periods, and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a Sponsor appointed study Adjudication Committee.

Overall Status Completed
Start Date 2008-12-31
Completion Date 2012-04-30
Primary Completion Date 2011-07-31
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS ITP: Baseline up to Week 96
Secondary Outcome
Measure Time Frame
ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS ITP: Baseline up to Week 96
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan ITP: Baseline up to Week 96
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria Time from Randomization up to 1217 days
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria ITP: Baseline up to week 96
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005) ITP: Baseline up to week 96
ITP: Number of New or Persisting Gd-enhanced Lesions ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Persisting Gd-enhanced Lesions OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of New or Enlarging T2 Lesions ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Enlarging T2 Lesions OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions ITP: Baseline, Week 96
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Changes From Baseline in Volume of T2 Lesions ITP: Baseline, Week 48 and 96
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions Baseline, Week 48
ITP: Number of T1 Hypointense Lesions ITP: Baseline, Week 48 and 96
OLMP: Number of T1 Hypointense Lesions OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions LTFU: Baseline, Week 48
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions OLMP: Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions LTFU: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions Baseline up to Week 48
ITP: Percentage of Participants With no New or Enlarging T2 Lesions ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions OLMP: Baseline up to 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions LTFU: Baseline up to Week 48
ITP: Percent Change From Baseline in Brain Volume ITP: Baseline, Week 48 and 96
OLMP: Percent Change From Baseline in Brain Volume OLMP: Baseline, Week 48 and 96
OLMP: Number of Relapses Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses Baseline up to Week 48
OLMP: Annualized Relapse Rate Baseline up to Week 96
OLMP: Percentage of Relapse-Free Participants Baseline up to Week 96
ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs ITP: Baseline up to Week 96
Enrollment 617
Condition
Intervention

Intervention Type: Drug

Intervention Name: Cladribine

Description: Cladribine tablets were administered until CDMS conversion, whichever occur first.

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo matched to cladribine tablets were administered.

Intervention Type: Drug

Intervention Name: Rebif® new formulation (RNF)

Description: Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.

Eligibility

Criteria:

Inclusion Criteria: - Male or female between 18 and 55 years old, inclusive - Weighed between 40 to 120 kilogram (kg), inclusive - Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic - Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI - Participant has EDSS 0 - 5.0 at Screening - Participant has no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or a comparable sensitive test according to local regulations/guidelines (if the Mantoux test is not available), and/or a chest X-ray - Participant has normal hematological parameters at Screening, as defined by the central laboratory that performed all the assessments - If female, she must: - be neither pregnant nor breast-feeding, nor attempting to conceive and - use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is less than 1 percent per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner, or - be post-menopausal or surgically sterilized (Note: for Danish sites only, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial) - Male participants must be willing to use contraception to avoid impregnating partners throughout the study, and for 90 days following the last dose of study medication - Be willing and able to comply with study procedures for the duration of the study - Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care - Participant has refused any treatment already available for clinically isolated syndrome (CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial Treatment Period of this study Exclusion Criteria: - Participant has a diagnosis of MS (per McDonald criteria, 2005) - Participant has any other disease that could better explain the participant's signs and symptoms - Participant has complete transverse myelitis or bilateral optic neuritis - Participant using or has used any other approved MS disease modifying drug (DMD) - Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1 - Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interfered with MRI timing the screening period could be extended accordingly. - Participant has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of normal - Participant suffered from current autoimmune disease other than MS - Participant suffered from psychiatric illness (including history of, or concurrent, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol - Participant suffered from major medical illness such as cardiac (for example angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine - Participant has a history of seizures not adequately controlled by medications - Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA) - Participant has any renal condition that would preclude the administration of gadolinium (for example acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] less than 30 milliliter per minute per 1.73 square meter [mL/min/1.73 m^2]) - Participant has a history of chronic or clinically significant hematological abnormalities - Participant has a history of active or chronic infectious disease or any disease that compromises immune function (for example human immunodeficiency virus positive [HIV+], human T-lymphotrophic virus [HTLV-1], Lyme disease, latent tuberculosis infection [LTBI] or TB, insulin-dependent diabetes). - Participant has previously been screened in this study (signed an informed consent) and then withdrawn - Participant has received any immunomodulatory or immunosuppressive therapy) at any time prior to Study Day 1, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy - Participant has received experimental MS treatment - Participant has a history of alcohol or drug abuse - Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen - Participant has inability to administer subcutaneous injections either by self or by caregiver - Participant has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years) - Participant has a positive stool hemoccult test at Screening

Gender:

All

Minimum Age:

18 Years

Maximum Age:

55 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Bettina Stubinski, MD Study Director Merck Serono S.A., Geneva
Location
Facility:
Hope Research Institute Medical Plaza LLC Desert Hills | Phoenix, Arizona, United States
Multiple Sclerosis Center Drive, Neurology Suite 701 | Newport Beach, California, United States
University of Colorado at Denver Health Sciences | Denver, Colorado, United States
Fort Collins Neurology | Fort Collins, Colorado, United States
MS Center of Brevard MIMA Centry Research Associates | Melbourne, Florida, United States
University of South Florida | Tampa, Florida, United States
MS Center of Atlanta | Atlanta, Georgia, United States
Bruce Hughes West Building | Des Moines, Iowa, United States
Michigan Neurology Associates | Clinton Township, Michigan, United States
Henry Ford Hospital | Detroit, Michigan, United States
University of Minnesota | Minneapolis, Minnesota, United States
Dennis Dietrich | Great Falls, Montana, United States
University of Medicine and Dentistry of New Jersey School of Neurology | Stratford, New Jersey, United States
Upstate Clinical Research LLC 3 | Albany, New York, United States
Neurological Specialists of Long Island | Great Neck, New York, United States
Multiple Sclerosis Center of Northeastern NY | New York, New York, United States
Comprehensive MS Care Clinic at South Shore Multiple Sclerosis | Patchogue, New York, United States
Carolinas Medical Center | Charlotte, North Carolina, United States
Meritcare Neuroscience Center Neurology | Fargo, North Dakota, United States
University of Cincinnati | Cincinnati, Ohio, United States
MS Center of Oklahoma | Oklahoma City, Oklahoma, United States
Neurology and Sleep Medicine | Bethlehem, Pennsylvania, United States
Swedish Medical Center Cherry Hill | Seattle, Washington, United States
Neurology & Neurological Association of Tacoma | Tacoma, Washington, United States
Instituto Medico Rodriguez Alfici | Godoy Cruz, Argentina
Fundacion Rosarina de Neurorehabilitacion | Rosario, Argentina
Krankenhaus der Barmherzigen Brüder | Linz, Austria
Algemeen Ziekenhuis St Jan | Brugge, Belgium
Cliniques Universitaires St-Luc | Brussels, Belgium
Hopital Erasme | Bruxelles, Belgium
CHU de Liege - Domaine Universitaire du Sart Tilman, | Liège, Belgium
Clinical Center University of Sarajevo | Sarajevo, Bosnia and Herzegovina
Military Medical Academy- Sofia (MMA) | Pleven, Bulgaria
MBAL Rousse AD 1st | Rousse, Bulgaria
Central Clinic Hospital | Sofia, Bulgaria
Military Medical Academy | Sofia, Bulgaria
National Heart Hospital | Sofia, Bulgaria
Second MHAT | Sofia, Bulgaria
Tokuda Hospital | Sofia, Bulgaria
University Hospital St Naum | Sofia, Bulgaria
Medical Centre Centromed 2000 | Veliko Tarnovo, Bulgaria
Ottawa General Hospital | Ottawa, Canada
General Hospital Varazdin | Varazdin, Croatia
University Hospital Zagreb | Zagreb, Croatia
Faculty Hospital Brno | Brno, Czechia
Neurological dept of Faculty | Hradec Kralove, Czechia
Fakultní nemocnice s poliklinikou Ostrava | Ostrava, Czechia
Faculty Hospital Motol | Prague, Czechia
Klinika Vseobecne | Prague, Czechia
Nemocnice Teplice | Teplice, Czechia
East Tallinn Central Hospital | Tallinn, Estonia
West Tallinn Central Hospital | Tallinn, Estonia
HUS Hyvinkaa Central Hospital | Hyvinkaa, Finland
OYKS Neurologian Klinikka | Oulu, Finland
Neurologian Klinikka Seinajoen Keskussairaala | Seinajoki, Finland
Tampere University Hospital | Tampere, Finland
Turun Yliopistollinen Keskussairaala Rakennus 3 1 | Turku, Finland
CHU de Lille | Lille Cedex, France
CHU de Nantes | Nantes, France
American Memorial Hospital | Reims Cedex, France
David Tatishvili Medical Center | Tbilisi, Georgia
Medical Center Health | Tbilisi, Georgia
S. Khechinashvili Tbilisi State Medical University | Tbilisi, Georgia
Universitaetsklinikum und Medizinische Fakultaet Heidelberg | Heidelberg, Germany
Philipps-Universitaet Marburg | Marburg, Germany
M S Ramaiah Medical College Hospital | Bangalore, Karnataka, India
St.John's Medical College and Hospital | Bangalore, Karnataka, India
Amrita Institute of Medical Sciences and Research | Kochi, Kerala, India
Kovai Medical Centre and Hospital | Coimbatore, India
Sanjay Gandhi Post Graduate Institute of Medical Sciences | Lucknow, India
Mallikatta Neuro and Research Centre | Mangalore, India
Ospedale Regionale Torrette | Ancona, Italy
Università de Bari | Bari, Italy
Ospedale Binaghi Centro Sclerosi Multipla | Cagliari, Italy
Azienda Ospedaliera Garibaldi | Catania, Italy
Dipartimento di Neuroscienze | Catania, Italy
Università G. D'Annunzio | Chieti, Italy
Ospedale San Antonio Abate | Gallarate, Italy
Universita degli Studi di Genova | Genova, Italy
Ospedale e casa di riposo P. Richiedei | Gussago, Italy
Ospedale San Raffaele | Milano, Italy
Dipartimento di Scienze Neurologiche | Napoli, Italy
Azienda Sanitaria Ospedaliera San Luigi Gonzaga | Orbassano, Italy
Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1 | Palermo, Italy
Istituto Neurologico C. Mondino | Pavia, Italy
Azienda Ospedaliera S. Camillo Forlanini | Roma, Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata | Roma, Italy
Università di Roma La Sapienza | Roma, Italy
National Cancer Center, Department of Neurology, | Gyeonggi-do, Korea, Republic of
Department of Neurology, 50 Ilwon-dong, Gangnam-gu | Seoul, Korea, Republic of
Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu | Seoul, Korea, Republic of
Seoul National University Hospital, Department of Neurology | Seoul, Korea, Republic of
Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center | Seoul, Korea, Republic of
American University of Beirut | Beirut, Lebanon
Clinic of Neurology "Klinicki Centar" | Skopje, North Macedonia
Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas | Bergen, Norway
Regionsykehuset I Trondheim, Nevrologisk avd. | Trondheim, Norway
10 Wojskowy Szpital Kliniczny | Bydgoszcz, Poland
Wojewodzki Szpital Specjalistyczny im. M. Kopernika | Gdansk, Poland
Niepubliczny Zespol Opieki Zdrowotnej | Krakow, Poland
Medical Academy of Lodz | Lodz, Poland
Panstwowy Szpital Kliniczny | Lublin, Poland
Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym | Olsztyn, Poland
Medical Academy | Poznan, Poland
Medical Academy II | Warsaw, Poland
Medical Academy | Warsaw, Poland
Hospital Fernando da Fonseca | Amadora, Portugal
Hospitais da Universidade de Coimbra | Coimbra, Portugal
Hospital de Santa Maria | Lisboa, Portugal
Centro Hospitalar de Coimbra | S. Martinho Do Bispo, Portugal
"Dr. Carol Davilla" Military Clinical Hospital | Bucharest, Romania
Centrul Medical SANA | Bucharest, Romania
Spitalul Clinic Judetean Mures | Targu-Mures, Romania
County Hospital Timisoara | Timisoara, Romania
Municipal Healthcare Institution "City Clinical Hospital #3" | Chelyabinsk, Russian Federation
State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1" | Ekaterinburg, Russian Federation
State Healthcare Institution "Kaluga Regional Hospital" | Kaluga, Russian Federation
State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health" | Kazan, Russian Federation
State Healthcare Institution "Kemerovo Regional Clinical Hospital" | Kemerovo, Russian Federation
State Medical Institution " Jursk Regional Clinical Hospital" | Kursk, Russian Federation
Moscow State Healthcare Institution City Clinical Hospital #11 | Moscow, Russian Federation
Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways" | Moscow, Russian Federation
State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic | Moscow, Russian Federation
Municipal Treatment Prophylactic Institution "City Hospital #33" | Nizhny Novgorod, Russian Federation
Federal State Institution " Siberian Reginal Medical Center of Roszdarv" | Novosibirsk, Russian Federation
State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences | Novosibirsk, Russian Federation
State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav" | Rostov-on-Don, Russian Federation
State Healthcare Institution "Rostov Region Clinical Hospital" | Rostov-on-Don, Russian Federation
State Educational Institution of Higher Professional Education "Military Medical Academy named after S. M. Korov of Dept of Defense of Russian Federation based on Clinic of Neurology of State Institution | Saint-Petersburg, Russian Federation
State Educational Institution of Higher Professional Education "Samara State Medical University of Roszdrav" on State Healthcare Institution "Samara Regional Clinical Hospital named after M. I. Kalinin" | Samara, Russian Federation
State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University | Saratov, Russian Federation
Regional State Healthcare Institution "State Smolensk Region Clinical Hospital" | Smolensk, Russian Federation
Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis | St Petersburg, Russian Federation
International Clinic and Hospital, Neurology | St Petersburg, Russian Federation
St. Petersburg State Healthcare Institution "Multifield City Hospital #2" | St. Petersburg, Russian Federation
State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav" | Tomsk, Russian Federation
Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital | Tyumen, Russian Federation
Vladimir Regional State Healthcare Institution "Regional Clinical Hospital" | Vladimir, Russian Federation
Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8" | Yaroslavl, Russian Federation
Clinical Centre of Serbia | Belgrade, Serbia
Hospital for Prevention and Treatment of Cerebro-Vascular Diseases | Belgrade, Serbia
Clinical Centre Niš | Niš, Serbia
National Neuroscience Institute (TTSH Campus) | Singapore, Singapore
Hospital Reina Sofia Cordoba | Cordoba, Spain
Hospital Universitario Nuestra Senora de la Candelaria | Sta. Cruz de Tenerife, Spain
Sahlgrenskasjukhuset | Goteborg, Sweden
Karolinska University Hospital | Stockholm, Sweden
Umea University Hospital | Umea, Sweden
Taipei Veterans | Taipei, Taiwan
Chang Gung Medical Foundation- Linkou Branch No5 | Taoyuan, Taiwan
Srinagarind Hospital | Khon Kaen, Thailand
Dokuz Eylul University | Izmir, Turkey
Ondokuz Mayis Universitesi | Samsun, Turkey
State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis | Kharkiv, Ukraine
Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology | Kiev, Ukraine
Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology | Vinnitsa, Ukraine
Rashid Hospital | Dubai, United Arab Emirates
Kings College London | London, United Kingdom
Location Countries

Argentina

Austria

Belgium

Bosnia and Herzegovina

Bulgaria

Canada

Croatia

Czechia

Estonia

Finland

France

Georgia

Germany

India

Italy

Korea, Republic of

Lebanon

North Macedonia

Norway

Poland

Portugal

Romania

Russian Federation

Serbia

Singapore

Spain

Sweden

Taiwan

Thailand

Turkey

Ukraine

United Arab Emirates

United Kingdom

United States

Verification Date

2021-02-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 12
Arm Group

Label: Cladribine 5.25 mg/kg (ITP)

Type: Experimental

Description: Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 milligrams per kilograms (mg/kg) during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.

Label: Cladribine 3.5 mg/kg (ITP)

Type: Experimental

Description: Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.

Label: Placebo (ITP)

Type: Placebo Comparator

Description: Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.

Label: Cladribine 5.25 mg/kg, Rebif (OLMP)

Type: Experimental

Description: Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.

Label: Cladribine 3.5 mg/kg, Rebif (OLMP)

Type: Experimental

Description: Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.

Label: Placebo, Rebif (OLMP)

Type: Experimental

Description: Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.

Label: Cladribine 5.25 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Type: Experimental

Description: Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Label: Cladribine 3.5 mg/kg, Rebif, Cladribine 3.5 mg/kg (LTFU)

Type: Experimental

Description: Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Label: Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)

Type: Experimental

Description: Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Label: Cladribine 5.25 mg/kg, Rebif (LTFU)

Type: Experimental

Description: Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Label: Cladribine 3.5 mg/kg, Rebif (LTFU)

Type: Experimental

Description: Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Label: Placebo, Rebif (LTFU)

Type: Experimental

Description: Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.

Acronym ORACLE MS
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

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

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