A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

A Phase 3, Multi-Center, Randomized, Double-Blind, Double-Dummy, Active Controlled, Parallel Group Study To Evaluate The Efficacy And Safety Of RPC1063 Administered Orally To Relapsing Multiple Sclerosis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02576717
• Other study ID #: RPC01-3001
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2015
• Est. completion date: January 5, 2023

Study information

• Verified date: January 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the trial is to determine the safety and efficacy of RPC1063 in patients with relapsing multiple sclerosis.

Description:

The trial is an open label extension study. Eligible patients from the RPC01-201, RPC01-301, and RPC01-1001 trials diagnosed with relapsing Multiple Sclerosis (RMS) will be enrolled to receive study drug until the end of the trial or until the Sponsor discontinues the development program.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2494
• Est. completion date: January 5, 2023
• Est. primary completion date: January 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Eligibility Criteria:

To be eligible to participate in this trial, patients must meet all of the following criteria:

1. Completed one of the parent trials

2. Does not have a condition that would require withdrawal from one of the parent trials

3. Has no conditions requiring treatment with a prohibited concomitant medication

4. Is not receiving treatment with any of the following drugs or interventions within the corresponding timeframe:

At Baseline (Day 1)

• CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin) Two weeks prior to Baseline (Day 1)

• Monoamine oxidase inhibitors (eg, selegiline, phenelzine)

5. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments

6. Female patients of childbearing potential:

Must agree to practice a highly effective method of contraception throughout the study until completion of the 90-day Safety Follow-up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly.

Acceptable methods of birth control in this study are the following:

• Combined hormonal (estrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal

• Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable

• Placement of an intrauterine device (IUD)

• Placement of an intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Vasectomised partner

• Sexual abstinence.

Exclusion Criteria:

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• RPC1063

Locations

Country	Name	City	State
Belarus	Local Institution - 904	Gomel
Belarus	Local Institution - 907	Grodno
Belarus	Local Institution - 901	Minsk
Belarus	Local Institution - 902	Minsk
Belarus	Local Institution - 903	Minsk
Belarus	Local Institution - 905	Vitebsk
Belarus	Local Institution - 906	Vitebsk
Belgium	Local Institution - 256	Brugge
Belgium	Local Institution - 255	Bruxelles
Belgium	Local Institution - 252	Montegnee
Bosnia and Herzegovina	Local Institution - 913	Banja Luka
Bosnia and Herzegovina	Local Institution - 911	Sarajevo
Bulgaria	Local Institution - 452	Sofia
Bulgaria	Local Institution - 453	Sofia
Bulgaria	Local Institution - 454	Sofia
Bulgaria	Local Institution - 455	Sofia
Bulgaria	Local Institution - 456	Sofia
Bulgaria	Local Institution - 457	Sofia
Bulgaria	Local Institution - 460	Sofia
Croatia	Local Institution - 923	Osijek
Croatia	Local Institution - 921	Zagreb
Croatia	Local Institution - 922	Zagreb
Croatia	Local Institution - 924	Zagreb
Estonia	Local Institution - 471	Tallinn
Estonia	Local Institution - 473	Tallinn
Estonia	Local Institution - 472	Tartu
Georgia	Local Institution - 301	Tbilisi
Georgia	Local Institution - 302	Tbilisi
Georgia	Local Institution - 303	Tbilisi
Georgia	Local Institution - 304	Tbilisi
Georgia	Local Institution - 306	Tbilisi
Germany	Local Institution - 487	Leipzig
Germany	Local Institution - 496	Potsdam
Germany	Local Institution - 488	Ulm
Greece	Local Institution - 551	Athens
Greece	Local Institution - 552	Athens
Greece	Local Institution - 553	Athens
Greece	Local Institution - 555	Thessaloniki
Hungary	Local Institution - 352	Budapest
Hungary	Local Institution - 356	Budapest
Hungary	Local Institution - 354	Esztergom
Hungary	Local Institution - 358	Kistarcsa
Hungary	Local Institution - 351	Nyiregyhaza
Italy	Local Institution - 654	Catania
Italy	Local Institution - 653	Cefalu
Italy	Local Institution - 655	Milan
Italy	Local Institution - 659	Montichiari
Italy	Local Institution - 651	Roma
Latvia	Local Institution - 561	Riga
Latvia	Local Institution - 562	Riga
Lithuania	Local Institution - 622	Kaunas	Kauno Apskritis
Lithuania	Local Institution - 621	Klaipeda
Moldova, Republic of	Local Institution - 931	Chisinau
Moldova, Republic of	Local Institution - 932	Chisinau
Moldova, Republic of	Local Institution - 933	Chisinau
New Zealand	Local Institution - 511	Christchurch
New Zealand	Local Institution - 510	Hamilton
Poland	Local Institution - 401	Bialystok
Poland	Local Institution - 423	Bydgoszcz
Poland	Local Institution - 406	Czeladz
Poland	Local Institution - 405	Gdansk
Poland	Local Institution - 432	Jaroslaw
Poland	Local Institution - 407	Katowice
Poland	Local Institution - 417	Katowice
Poland	Local Institution - 426	Katowice
Poland	Local Institution - 427	Katowice
Poland	Local Institution - 424	Kielce
Poland	Local Institution - 404	Konstancin Jeziorna
Poland	Local Institution - 414	Krakow
Poland	Local Institution - 411	Lódzkie
Poland	Local Institution - 412	Lublin
Poland	Local Institution - 420	Lublin
Poland	Local Institution - 429	Lublin
Poland	Local Institution - 431	Mazowieckie
Poland	Local Institution - 415	Olsztyn
Poland	Local Institution - 421	Plewiska
Poland	Local Institution - 425	Pomorskie
Poland	Local Institution - 408	Poznan
Poland	Local Institution - 418	Poznan
Poland	Local Institution - 433	Rybnik
Poland	Local Institution - 435	Rzeszow
Poland	Local Institution - 419	Szczecin
Poland	Local Institution - 402	Warminsko-mazurskie
Poland	Local Institution - 410	Warsaw
Poland	Local Institution - 403	Warszawa
Poland	Local Institution - 413	Warszawa
Poland	Local Institution - 422	Warszawa
Poland	Local Institution - 428	Warszawa
Poland	Local Institution - 434	Warszawa	Mazowieckie
Portugal	Local Institution - 772	Braga
Portugal	Local Institution - 775	Coimbra
Portugal	Local Institution - 773	Torres Vedras
Romania	Local Institution - 503	Brasov
Romania	Local Institution - 504	Bucharest
Romania	Local Institution - 509	Bucharest
Romania	Local Institution - 520	Bucharest
Romania	Local Institution - 502	Campulung
Romania	Local Institution - 508	Cluj Napoca
Romania	Local Institution - 501	Cluj-Napoca
Romania	Local Institution - 507	Constanta
Romania	Local Institution - 506	Timisoara
Serbia	Local Institution - 601	Belgrade
Serbia	Local Institution - 602	Belgrade
Serbia	Local Institution - 603	Belgrade
Serbia	Local Institution - 604	Belgrade
Serbia	Local Institution - 605	Kragujevac
Serbia	Local Institution - 606	Nis
Slovakia	Local Institution - 946	Bratislava
Slovakia	Local Institution - 942	Lucenec
Slovakia	Local Institution - 945	Trnava
South Africa	Local Institution - 953	Pretoria
Spain	Local Institution - 756	Barcelona
Spain	Local Institution - 758	Barcelona
Spain	Local Institution - 761	Bilbao
Spain	Local Institution - 760	Girona
Spain	Local Institution - 757	Madrid
Spain	Local Institution - 754	Majadahonda
Spain	Local Institution - 764	Pamplona/ Navarra
Spain	Local Institution - 759	San Sebastian
Spain	Local Institution - 766	Sant Joan Despí
Spain	Local Institution - 755	Sevillla
Spain	Local Institution - 752	Valencia
Spain	Local Institution - 767	Valencia
Sweden	Local Institution - 780	Goteborg
Ukraine	Local Institution - 823	Cherkasy
Ukraine	Local Institution - 805	Chernihiv
Ukraine	Local Institution - 830	Chernihiv
Ukraine	Local Institution - 813	Chernivtsi
Ukraine	Local Institution - 802	Dnipropetrovsk
Ukraine	Local Institution - 815	Dnipropetrovsk
Ukraine	Local Institution - 801	Ivano Frankivsk
Ukraine	Local Institution - 829	Ivano-Frankivsk
Ukraine	Local Institution - 814	Kharkiv
Ukraine	Local Institution - 827	Kharkiv
Ukraine	Local Institution - 832	Kharkiv
Ukraine	Local Institution - 811	Kherson
Ukraine	Local Institution - 803	Kyiv
Ukraine	Local Institution - 818	Kyiv
Ukraine	Local Institution - 822	Kyiv
Ukraine	Local Institution - 824	Kyiv
Ukraine	Local Institution - 817	Lutsk
Ukraine	Local Institution - 812	Lviv
Ukraine	Local Institution - 821	Lviv
Ukraine	Local Institution - 804	Odesa
Ukraine	Local Institution - 810	Odesa
Ukraine	Local Institution - 831	Odesa
Ukraine	Local Institution - 826	Poltava
Ukraine	Local Institution - 820	Uzhhorod
Ukraine	Local Institution - 809	Vinnytsia
Ukraine	Local Institution - 825	Zaporizhia
Ukraine	Local Institution - 828	Zaporizhzhia
Ukraine	Local Institution - 806	Zaporizhzhya
Ukraine	Local Institution - 819	Zhytomyr
United Kingdom	Local Institution - 965	East Sussex
United Kingdom	Local Institution - 963	Inverness
United Kingdom	Local Institution - 964	Sheffield
United States	Local Institution - 110	Berkeley	California
United States	Local Institution - 103	Fresno	California
United States	Local Institution - 137	Golden Valley	Minnesota
United States	Local Institution - 141	Kirkland	Washington
United States	Local Institution - 144	Knoxville	Tennessee
United States	Local Institution - 170	Las Vegas	Nevada
United States	Local Institution - 122	Long Beach	California
United States	Local Institution - 138	Lubbock	Texas
United States	Local Institution - 114	Maitland	Florida
United States	Local Institution - 115	Phoenix	Arizona
United States	Local Institution - 118	Phoenix	Arizona
United States	Local Institution - 123	Port Charlotte	Florida
United States	Local Institution - 143	Raleigh	North Carolina
United States	Local Institution - 179	Round Rock	Texas
United States	Local Institution - 112	Sacramento	California
United States	Local Institution - 120	San Francisco	California
United States	Local Institution - 124	Sunrise	Florida
United States	Local Institution - 147	Tampa	Florida
United States	Local Institution - 107	Westerville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Croatia,  Estonia,  Georgia,  Germany,  Greece,  Hungary,  Italy,  Latvia,  Lithuania,  Moldova, Republic of,  New Zealand,  Poland,  Portugal,  Romania,  Serbia,  Slovakia,  South Africa,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Adverse Events (AEs)	An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.	From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
Primary	Number of Participants Experiencing Serious Adverse Events (SAEs)	A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.	From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
Primary	Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation	An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.	From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
Primary	Number of Participants Experiencing Adverse Events (AEs) Leading to Withdrawal	An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.	From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
Primary	Number of Participants Experiencing Adverse Events (AEs) of Special Interest	An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.	From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
Primary	Number of Participants With Abnormalities in Blood Absolute Lymphocyte Count (ALC)	An absolute lymphocyte count (ALC) is a part of a blood test that measures the number of lymphocytes, a type of white blood cell, in the blood. Lymphocytes help fight infections and diseases. Reductions in ALC levels for participants in this study is expected and is a primary pharmacodynamic effect of RPC1063.; LLN = Lower limit of normal	From first dose up until last dose of study treatment (up to approximately 82 months)
Primary	Number of Participants With Abnormalities in White Blood Cell Count (WBC)	A white blood cell count is a part of a blood test that measures the number of white blood cells in the blood. White blood cells help fight infections and diseases.; LLN = Lower limit of normal	From first dose up until last dose of study treatment (up to approximately 82 months)
Primary	Number of Participants With Abnormalities in Blood Absolute Neutrophil Count (ANC)	An absolute neutrophil count is a part of a blood test that measures the number of neutrophils, a type of white blood cell, in the blood. Neutrophils help fight infections and diseases.	From first dose up until last dose of study treatment (up to approximately 82 months)
Primary	Number of Participants With Abnormalities in Specific Liver Function Tests	The number of participants with laboratory abnormalities in specific liver tests above ULN by category. ULN = Upper Limit of Normal	From first dose up until last dose of study treatment (up to approximately 82 months)
Primary	Number of Participants With Electrocardiogram (ECG) Result Abnormalities	An electrocardiogram (ECG) measures electrical activity of the heart to detect cardiac problems.	From first dose to 28-days post last dose (an average of 63 months up to a max of 83 months)
Primary	Number of Participants With Clinically Relevant Abnormalities in Vital Signs	Vital signs included body temperature, sitting heart rate/pulse (HR), sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP).; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and 60 months after first dose of study therapy
Primary	Number of Participants With Physical Examination Abnormalities	The number of participants with abnormal physical examination results. The assessments included abdominal, extremity, head, heart, lungs, neck, neurological non-MS, other and skin assessments.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 84 months post first dose.
Primary	Number of Participants Self-Identifying Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs.; Results are displayed as the number of participants who answered "Yes" to at least one of the 10 questions in the suicidal ideation or suicidal behavior section.; Ideation from 1 (wishing to be dead) - 5 (Active suicidal ideation with specific plan and intent) Behavior from 6 (Preparatory acts or behavior) - 10 (Completed suicide). Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 3 months thereafter up until 78 months post first dose.
Primary	Number of Participants With Changes in Suicidality From Last Day on Treatment Per the Columbia-Suicide Severity Rating Scale (C-SSRS)	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs.; Results are displayed as the number of participants who answered "Yes" to at least one of the 10 questions in the suicidal ideation or suicidal behavior section.; Ideation from 1 (wishing to be dead) - 5 (Active suicidal ideation with specific plan and intent) Behavior from 6 (Preparatory acts or behavior) - 10 (Completed suicide).	1, 4, 7, 14, 21, 28, and 90 days post last dose.
Primary	Change in Physician's Withdrawal Checklist (PWC-20) Total Score From Last Day on Treatment	The PWC-20 is a rater-administered 20-item scale to assess signs and symptoms of withdrawal. Twenty items are rated on a 4-point scale as not present (0 points), mild (1 point), moderate (2 points), or severe (3 points). The points from all items are calculated as a total score. Higher scores indicate more severe withdrawal symptoms.	1, 4, 7, 14, 21, and 90 days post last dose.
Primary	Change in Hospital Anxiety and Depression Scale (HADS) Score From Last Day on Treatment	The HADS is a validated patient reported outcome for assessing anxiety and depression. It consists of 14 items in total, 7 items related to anxiety and 7 items related to depression. For each item patients select a statement (valued at 0 to 3 points) that closest matches their own feeling over the past week. Separate total scores for anxiety and depression are derived by adding up points. Total scores can range from 0 to 21 points. Higher scores indicate more severe anxiety and depression and scores of 8 to 10 are generally considered indicative of borderline anxiety/depression disorders and scores of 11 and higher are generally considered indicative of anxiety/depression disorders.	1, 4, 7, 14, 21, and 90 days post last dose.
Primary	Changes in Epworth Sleepiness Scale (ESS) Score From Last Day on Treatment	The ESS is a validated self administered questionnaire with 8 questions. Respondents rate on a 4-point scale (0 to 3) their chances of dozing off or falling asleep while engaged in 8 different activities. The ESS score is the sum of 8 item scores and can range from 0 to 24 points. Higher scores indicate more daytime sleepiness.	1, 4, 7, 14, 21, and 90 days post last dose.
Primary	Changes in Vital Sign Values From Last Day on Treatment	Vital signs included sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP).	1, 4, 7, 14, 21, 28, and 90 days post last dose.
Secondary	Annualized Relapse Rate (ARR)	The Annualized Relapse Rate (ARR) is the average number of relapses per study arm in one year. A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by a relatively stable or improving neurological state of at least 30 days. The adjusted ARR was based on the negative binomial regression model with parent treatment group, adjusted for region (Eastern Europe vs Rest of World), age at parent baseline, and the parent baseline number of gadolinium-enhanced (GdE) lesions. The natural log transformation of time on treatment was used as an offset term to adjust for participants having different exposure times.	From first dose up until last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months)
Secondary	Time to First Relapse (TFR)	The time between first dose of study treatment and first relapse if experienced by a participant. A participant was censored if follow-up ended before a relapse occurred, whether due to the participant completing study, withdrawing from the study, or due to the cutoff of data collection for the analysis. The censor date was the date of the end of study or the date of the data cutoff for participant who were ongoing. Participants who withdrew from the study after the baseline visit were censored at the last known date while on study. Based on Kaplan-Meier product limit estimates.	Overall: From first dose to first relapse, last dose, or data-cutoff date, whichever occurred first (up to approx 87 months); Visits: 2 weeks post first dose, 3 months post first dose, and every 3 months thereafter up until 81 months post first dose.
Secondary	Number of Participants Who Were Relapse Free	The number of participants who did not experience relapse. A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by a relatively stable or improving neurological state of at least 30 days.	From first dose to last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months)
Secondary	Average Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions Per Scan at Each Visit	Adjusted Mean of new enlarging T2 lesions per scan at each visit. Based on a negative binomial regression model, adjusted for parent study, region (Eastern Europe vs. Rest of the World), age at Baseline, and baseline number of GdE lesions.; T2 Magnetic Resonance Imaging (MRI) sequences are used to highlight areas of demyelination in brain neurons, which happens when the outer layer of the neurons is damaged due to multiple sclerosis (MS) activity. T2 sequences can be used to count the total number of MS lesions, which look like bright white spots on T2 sequences, and can be called "hyperintense".	At 12 months post first dose and every 12 months thereafter up until 72 months post first dose.
Secondary	Average Number of Gadolinium-Enhanced (GdE) Brain MRI Lesions Per Scan at Each Visit	Number of gadolinium-enhanced (GdE) (also called GdE enhanced T1) brain MRI lesions per scan at each visit.; Increased numbers of GdE lesions indicates an increase in the in the amount of active inflammation at the site and may be indicative of progressive disease.; Based on a negative binomial regression model, adjusted for parent study, region (Eastern Europe vs. Rest of the World), age at Baseline, and Baseline number of GdE lesions.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 72 months post first dose.
Secondary	Time to Onset of Disability Progression as Defined by a Sustained Worsening in Expanded Disability Status Scale (EDSS)	Multiple sclerosis (MS) disability progression is defined as a sustained worsening in EDSS of 1.0 points or more from baseline, confirmed after a 3-month and 6-month period. The EDSS is a standardized method, widely accepted, numerical scale used to evaluate disability in people with multiple sclerosis (MS). The EDSS is evaluated according to signs and symptoms observed during a standard neurological examination. These clinical observations are classified in 7 FS scales, each of them grading signs and symptoms for different neurological functions: pyramidal, cerebellar, brainstem, sensory, bowel or bladder, visual, and cerebral.; Derived using Kaplan-Meier estimates.	At 3 and 6 months post first dose.
Secondary	Number of Participants Free of Gadolinium-Enhanced (GdE) Brain Lesions at Each Visit	Number of participants without gadolinium enhanced (GdE) brain MRI lesions at each visit. Increased numbers of GdE lesions indicates an increase in the in the amount of active inflammation at the site and may be indicative of progressive disease.; Based on cumulative number of GdE lesions at a participant level.	At baseline and every 12 months thereafter up until 72 months post first dose.
Secondary	Number of Participants Free of New or Enlarging T2 Lesions at Each Visit	Number of participants without new or enlarging T2 brain MRI lesions at each visit. Some multiple Sclerosis (MS) lesions appear as bright spots in a T2-weighted MRI scan - these are called T2 lesions. The presence of new or larger T2 lesions may mean the participant is at higher risk of disability and may have a less favorable long-term outcome.; Based on cumulative number of new or enlarging T2 lesions at a participant level.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 72 months post first dose.
Secondary	Percent Change in Normalized Brain Volume (Atrophy) on Brain MRI Scans From Baseline at Each Visit	Percent change in normalized brain volume (Atrophy) on brain MRI scans from baseline at each visit. Brain atrophy can be seen in the earliest stages of multiple sclerosis (MS) and is a reliable predictor of future physical and cognitive disability.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until approximately 87 months post first dose.
Secondary	Change in Multiple Sclerosis Functional Composite (MSFC) Score From Baseline at Each Applicable Visit	The Multiple Sclerosis Functional Composite (MSFC) is a 3-part tool to measure disability progression in those with multiple sclerosis (MS). It assesses leg, arm, hand, and cognitive function using 3 individual scales: - The Timed 25-Foot Walk: To measure leg function - The 9-Hole Peg Test: To measure arm and hand function - The Symbol Digit Modalities Test (SDMT): To measure cognitive processing speed, flexibility, and calculation ability. Scores from each of the three are converted into Z-scores and averaged to create an overall composite score. The Low-Contrast Letter Acuity Test (LCLA) is performed with the MSFC using a set of charts to assess low contrast visual acuity. Each chart corresponds to a different contrast level, and charts are scored based on the number of letters identified correctly. A Z-score of 0 represents the population mean. Standard deviations above the mean represent a better outcome. Baseline refers to assessments on or before receiving study treatment.	At baseline and every 12 months thereafter up until 84 months post first dose.
Secondary	Change in Multiple Sclerosis Quality of Life 54 Score From Baseline at Each Applicable Visit	The Multiple Sclerosis Quality of Life 54 (MSQOL-54) questionnaire is a health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). This 54-item instrument generates 12 subscales along with two summary scores (physical health and mental health - derived from a weighted combination of scale scores), and two additional single-item measures. The subscales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The MSQOL-54 items are transformed to 0-100 scores, and final scores are obtained by averaging items within the scales. The overall quality of life is assessed in question 54, which is scored on a scale of 0-100. Higher scores indicate better health-related quality of life. Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 84 months post first dose.
Secondary	Change From Baseline in Volume of Gadolinium Enhanced T1 Lesions	Change from baseline in volume of gadolinium enhanced T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or "black holes" on a type of MRI scan. The growth of T1 lesions may mean the participant's Multiple Sclerosis (MS) is progressing.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 72 months post first dose.
Secondary	Change From Baseline in Volume of T2 Lesions	Some multiple Sclerosis (MS) lesions appear as bright spots in a T2-weighted MRI scan - these are called T2 lesions. Larger T2 lesions may mean the participant is at higher risk of disability and may have a less favorable long-term outcome.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 72 months post first dose.
Secondary	Change From Baseline in Volume of Unenhancing T1 Lesions	Change from baseline in volume of unenhancing T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or "black holes" on a type of MRI scan. The growth of T1 lesions may mean the participant's Multiple Sclerosis (MS) is progressing.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 72 months post first dose.
Secondary	Cumulative Number of New Unenhancing T1 Lesions	Number of new unenhancing T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or "black holes" on a type of MRI scan. The appearance of new T1 lesions may mean the participant's MS is progressing.; Derived as the cumulative number of new or enlarging T1 lesions relative to baseline at a participant level.; Baseline refers to assessments made on or before the first day participants received study treatment.	At baseline and every 12 months thereafter up until 72 months post first dose.

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting