Clinical trial NCT02576717: A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: MS
RMS
Multiple Sclerosis
Relapsing Multiple Sclerosis
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2015-10-15
Enrollment: 2494
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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:

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
measure: Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
timeFrame: From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
measure: Number of Participants Experiencing Adverse Events (AEs) Leading to Withdrawal
timeFrame: From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
measure: Number of Participants Experiencing Adverse Events (AEs) of Special Interest
timeFrame: From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months)
measure: Number of Participants With Abnormalities in Blood Absolute Lymphocyte Count (ALC)
timeFrame: From first dose up until last dose of study treatment (up to approximately 82 months)
measure: Number of Participants With Abnormalities in White Blood Cell Count (WBC)
timeFrame: From first dose up until last dose of study treatment (up to approximately 82 months)
measure: Number of Participants With Abnormalities in Blood Absolute Neutrophil Count (ANC)
timeFrame: From first dose up until last dose of study treatment (up to approximately 82 months)
measure: Number of Participants With Abnormalities in Specific Liver Function Tests
timeFrame: From first dose up until last dose of study treatment (up to approximately 82 months)
measure: Number of Participants With Electrocardiogram (ECG) Result Abnormalities
timeFrame: From first dose to 28-days post last dose (an average of 63 months up to a max of 83 months)
measure: Number of Participants With Clinically Relevant Abnormalities in Vital Signs
timeFrame: At baseline and 60 months after first dose of study therapy
measure: Number of Participants With Physical Examination Abnormalities
timeFrame: At baseline and every 12 months thereafter up until 84 months post first dose.
measure: Number of Participants Self-Identifying Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: At baseline and every 3 months thereafter up until 78 months post first dose.
measure: Number of Participants With Changes in Suicidality From Last Day on Treatment Per the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: 1, 4, 7, 14, 21, 28, and 90 days post last dose.
measure: Change in Physician's Withdrawal Checklist (PWC-20) Total Score From Last Day on Treatment
timeFrame: 1, 4, 7, 14, 21, and 90 days post last dose.
measure: Change in Hospital Anxiety and Depression Scale (HADS) Score From Last Day on Treatment
timeFrame: 1, 4, 7, 14, 21, and 90 days post last dose.
measure: Changes in Epworth Sleepiness Scale (ESS) Score From Last Day on Treatment
timeFrame: 1, 4, 7, 14, 21, and 90 days post last dose.
measure: Changes in Vital Sign Values From Last Day on Treatment
timeFrame: 1, 4, 7, 14, 21, 28, and 90 days post last dose.
Secondary outcomes:
measure: Annualized Relapse Rate (ARR)
timeFrame: From first dose up until last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months)
measure: Time to First Relapse (TFR)
timeFrame: 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.
measure: Number of Participants Who Were Relapse Free
timeFrame: From first dose to last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months)
measure: Average Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions Per Scan at Each Visit
timeFrame: At 12 months post first dose and every 12 months thereafter up until 72 months post first dose.
measure: Average Number of Gadolinium-Enhanced (GdE) Brain MRI Lesions Per Scan at Each Visit
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
measure: Time to Onset of Disability Progression as Defined by a Sustained Worsening in Expanded Disability Status Scale (EDSS)
timeFrame: At 3 and 6 months post first dose.
measure: Number of Participants Free of Gadolinium-Enhanced (GdE) Brain Lesions at Each Visit
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
measure: Number of Participants Free of New or Enlarging T2 Lesions at Each Visit
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
measure: Percent Change in Normalized Brain Volume (Atrophy) on Brain MRI Scans From Baseline at Each Visit
timeFrame: At baseline and every 12 months thereafter up until approximately 87 months post first dose.
measure: Change in Multiple Sclerosis Functional Composite (MSFC) Score From Baseline at Each Applicable Visit
timeFrame: At baseline and every 12 months thereafter up until 84 months post first dose.
measure: Change in Multiple Sclerosis Quality of Life 54 Score From Baseline at Each Applicable Visit
timeFrame: At baseline and every 12 months thereafter up until 84 months post first dose.
measure: Change From Baseline in Volume of Gadolinium Enhanced T1 Lesions
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
measure: Change From Baseline in Volume of T2 Lesions
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
measure: Change From Baseline in Volume of Unenhancing T1 Lesions
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
measure: Cumulative Number of New Unenhancing T1 Lesions
timeFrame: At baseline and every 12 months thereafter up until 72 months post first dose.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Local Institution - 115
state: Arizona
city: Phoenix
country: United States
facility: Local Institution - 118
state: Arizona
city: Berkeley
country: United States
facility: Local Institution - 110
state: California
city: Fresno
country: United States
facility: Local Institution - 103
state: California
city: Long Beach
country: United States
facility: Local Institution - 122
state: California
city: Sacramento
country: United States
facility: Local Institution - 112
state: California
city: San Francisco
country: United States
facility: Local Institution - 120
state: California
city: Maitland
country: United States
facility: Local Institution - 114
state: Florida
city: Port Charlotte
country: United States
facility: Local Institution - 123
state: Florida
city: Sunrise
country: United States
facility: Local Institution - 124
state: Florida
city: Tampa
country: United States
facility: Local Institution - 147
state: Florida
city: Golden Valley
country: United States
facility: Local Institution - 137
state: Minnesota
city: Las Vegas
country: United States
facility: Local Institution - 170
state: Nevada
city: Raleigh
country: United States
facility: Local Institution - 143
state: North Carolina
city: Westerville
country: United States
facility: Local Institution - 107
state: Ohio
city: Knoxville
country: United States
facility: Local Institution - 144
state: Tennessee
city: Lubbock
country: United States
facility: Local Institution - 138
state: Texas
city: Round Rock
country: United States
facility: Local Institution - 179
state: Texas
city: Kirkland
country: United States
facility: Local Institution - 141
state: Washington
city: Gomel
country: Belarus
facility: Local Institution - 904
city: Grodno
country: Belarus
facility: Local Institution - 907
city: Minsk
country: Belarus
facility: Local Institution - 902
city: Minsk
country: Belarus
facility: Local Institution - 901
city: Minsk
country: Belarus
facility: Local Institution - 903
city: Vitebsk
country: Belarus
facility: Local Institution - 905
city: Vitebsk
country: Belarus
facility: Local Institution - 906
city: Brugge
country: Belgium
facility: Local Institution - 256
city: Bruxelles
country: Belgium
facility: Local Institution - 255
city: Montegnee
country: Belgium
facility: Local Institution - 252
city: Banja Luka
country: Bosnia and Herzegovina
facility: Local Institution - 913
city: Sarajevo
country: Bosnia and Herzegovina
facility: Local Institution - 911
city: Sofia
country: Bulgaria
facility: Local Institution - 453
city: Sofia
country: Bulgaria
facility: Local Institution - 454
city: Sofia
country: Bulgaria
facility: Local Institution - 452
city: Sofia
country: Bulgaria
facility: Local Institution - 456
city: Sofia
country: Bulgaria
facility: Local Institution - 457
city: Sofia
country: Bulgaria
facility: Local Institution - 460
city: Sofia
country: Bulgaria
facility: Local Institution - 455
city: Osijek
country: Croatia
facility: Local Institution - 923
city: Zagreb
country: Croatia
facility: Local Institution - 921
city: Zagreb
country: Croatia
facility: Local Institution - 922
city: Zagreb
country: Croatia
facility: Local Institution - 924
city: Tallinn
country: Estonia
facility: Local Institution - 473
city: Tallinn
country: Estonia
facility: Local Institution - 471
city: Tartu
country: Estonia
facility: Local Institution - 472
city: Tbilisi
country: Georgia
facility: Local Institution - 301
city: Tbilisi
country: Georgia
facility: Local Institution - 302
city: Tbilisi
country: Georgia
facility: Local Institution - 304
city: Tbilisi
country: Georgia
facility: Local Institution - 306
city: Tbilisi
country: Georgia
facility: Local Institution - 303
city: Leipzig
country: Germany
facility: Local Institution - 487
city: Potsdam
country: Germany
facility: Local Institution - 496
city: Ulm
country: Germany
facility: Local Institution - 488
city: Athens
country: Greece
facility: Local Institution - 552
city: Athens
country: Greece
facility: Local Institution - 553
city: Athens
country: Greece
facility: Local Institution - 551
city: Thessaloniki
country: Greece
facility: Local Institution - 555
city: Budapest
country: Hungary
facility: Local Institution - 352
city: Budapest
country: Hungary
facility: Local Institution - 356
city: Esztergom
country: Hungary
facility: Local Institution - 354
city: Kistarcsa
country: Hungary
facility: Local Institution - 358
city: Nyiregyhaza
country: Hungary
facility: Local Institution - 351
city: Catania
country: Italy
facility: Local Institution - 654
city: Cefalu
country: Italy
facility: Local Institution - 653
city: Milan
country: Italy
facility: Local Institution - 655
city: Montichiari
country: Italy
facility: Local Institution - 659
city: Roma
country: Italy
facility: Local Institution - 651
city: Riga
country: Latvia
facility: Local Institution - 562
city: Riga
country: Latvia
facility: Local Institution - 561
city: Kaunas
country: Lithuania
facility: Local Institution - 622
state: Kauno Apskritis
city: Klaipeda
country: Lithuania
facility: Local Institution - 621
city: Chisinau
country: Moldova, Republic of
facility: Local Institution - 932
city: Chisinau
country: Moldova, Republic of
facility: Local Institution - 931
city: Chisinau
country: Moldova, Republic of
facility: Local Institution - 933
city: Christchurch
country: New Zealand
facility: Local Institution - 511
city: Hamilton
country: New Zealand
facility: Local Institution - 510
city: Warszawa
country: Poland
facility: Local Institution - 434
state: Mazowieckie
city: Bialystok
country: Poland
facility: Local Institution - 401
city: Bydgoszcz
country: Poland
facility: Local Institution - 423
city: Czeladz
country: Poland
facility: Local Institution - 406
city: Gdansk
country: Poland
facility: Local Institution - 405
city: Jaroslaw
country: Poland
facility: Local Institution - 432
city: Katowice
country: Poland
facility: Local Institution - 417
city: Katowice
country: Poland
facility: Local Institution - 427
city: Katowice
country: Poland
facility: Local Institution - 426
city: Katowice
country: Poland
facility: Local Institution - 407
city: Kielce
country: Poland
facility: Local Institution - 424
city: Konstancin Jeziorna
country: Poland
facility: Local Institution - 404
city: Krakow
country: Poland
facility: Local Institution - 414
city: Lublin
country: Poland
facility: Local Institution - 429
city: Lublin
country: Poland
facility: Local Institution - 412
city: Lublin
country: Poland
facility: Local Institution - 420
city: Lódzkie
country: Poland
facility: Local Institution - 411
city: Mazowieckie
country: Poland
facility: Local Institution - 431
city: Olsztyn
country: Poland
facility: Local Institution - 415
city: Plewiska
country: Poland
facility: Local Institution - 421
city: Pomorskie
country: Poland
facility: Local Institution - 425
city: Poznan
country: Poland
facility: Local Institution - 408
city: Poznan
country: Poland
facility: Local Institution - 418
city: Rybnik
country: Poland
facility: Local Institution - 433
city: Rzeszow
country: Poland
facility: Local Institution - 435
city: Szczecin
country: Poland
facility: Local Institution - 419
city: Warminsko-mazurskie
country: Poland
facility: Local Institution - 402
city: Warsaw
country: Poland
facility: Local Institution - 410
city: Warszawa
country: Poland
facility: Local Institution - 428
city: Warszawa
country: Poland
facility: Local Institution - 422
city: Warszawa
country: Poland
facility: Local Institution - 403
city: Warszawa
country: Poland
facility: Local Institution - 413
city: Braga
country: Portugal
facility: Local Institution - 772
city: Coimbra
country: Portugal
facility: Local Institution - 775
city: Torres Vedras
country: Portugal
facility: Local Institution - 773
city: Brasov
country: Romania
facility: Local Institution - 503
city: Bucharest
country: Romania
facility: Local Institution - 509
city: Bucharest
country: Romania
facility: Local Institution - 504
city: Bucharest
country: Romania
facility: Local Institution - 520
city: Campulung
country: Romania
facility: Local Institution - 502
city: Cluj Napoca
country: Romania
facility: Local Institution - 508
city: Cluj-Napoca
country: Romania
facility: Local Institution - 501
city: Constanta
country: Romania
facility: Local Institution - 507
city: Timisoara
country: Romania
facility: Local Institution - 506
city: Belgrade
country: Serbia
facility: Local Institution - 602
city: Belgrade
country: Serbia
facility: Local Institution - 603
city: Belgrade
country: Serbia
facility: Local Institution - 604
city: Belgrade
country: Serbia
facility: Local Institution - 601
city: Kragujevac
country: Serbia
facility: Local Institution - 605
city: Nis
country: Serbia
facility: Local Institution - 606
city: Bratislava
country: Slovakia
facility: Local Institution - 946
city: Lucenec
country: Slovakia
facility: Local Institution - 942
city: Trnava
country: Slovakia
facility: Local Institution - 945
city: Pretoria
country: South Africa
facility: Local Institution - 953
city: Barcelona
country: Spain
facility: Local Institution - 756
city: Barcelona
country: Spain
facility: Local Institution - 758
city: Bilbao
country: Spain
facility: Local Institution - 761
city: Girona
country: Spain
facility: Local Institution - 760
city: Madrid
country: Spain
facility: Local Institution - 757
city: Majadahonda
country: Spain
facility: Local Institution - 754
city: Pamplona/ Navarra
country: Spain
facility: Local Institution - 764
city: San Sebastian
country: Spain
facility: Local Institution - 759
city: Sant Joan Despí
country: Spain
facility: Local Institution - 766
city: Sevillla
country: Spain
facility: Local Institution - 755
city: Valencia
country: Spain
facility: Local Institution - 767
city: Valencia
country: Spain
facility: Local Institution - 752
city: Goteborg
country: Sweden
facility: Local Institution - 780
city: Cherkasy
country: Ukraine
facility: Local Institution - 823
city: Chernihiv
country: Ukraine
facility: Local Institution - 830
city: Chernihiv
country: Ukraine
facility: Local Institution - 805
city: Chernivtsi
country: Ukraine
facility: Local Institution - 813
city: Dnipropetrovsk
country: Ukraine
facility: Local Institution - 802
city: Dnipropetrovsk
country: Ukraine
facility: Local Institution - 815
city: Ivano Frankivsk
country: Ukraine
facility: Local Institution - 801
city: Ivano-Frankivsk
country: Ukraine
facility: Local Institution - 829
city: Kharkiv
country: Ukraine
facility: Local Institution - 814
city: Kharkiv
country: Ukraine
facility: Local Institution - 827
city: Kharkiv
country: Ukraine
facility: Local Institution - 832
city: Kherson
country: Ukraine
facility: Local Institution - 811
city: Kyiv
country: Ukraine
facility: Local Institution - 822
city: Kyiv
country: Ukraine
facility: Local Institution - 803
city: Kyiv
country: Ukraine
facility: Local Institution - 818
city: Kyiv
country: Ukraine
facility: Local Institution - 824
city: Lutsk
country: Ukraine
facility: Local Institution - 817
city: Lviv
country: Ukraine
facility: Local Institution - 812
city: Lviv
country: Ukraine
facility: Local Institution - 821
city: Odesa
country: Ukraine
facility: Local Institution - 810
city: Odesa
country: Ukraine
facility: Local Institution - 831
city: Odesa
country: Ukraine
facility: Local Institution - 804
city: Poltava
country: Ukraine
facility: Local Institution - 826
city: Uzhhorod
country: Ukraine
facility: Local Institution - 820
city: Vinnytsia
country: Ukraine
facility: Local Institution - 809
city: Zaporizhia
country: Ukraine
facility: Local Institution - 825
city: Zaporizhzhia
country: Ukraine
facility: Local Institution - 828
city: Zaporizhzhya
country: Ukraine
facility: Local Institution - 806
city: Zhytomyr
country: Ukraine
facility: Local Institution - 819
city: East Sussex
country: United Kingdom
facility: Local Institution - 965
city: Inverness
country: United Kingdom
facility: Local Institution - 963
city: Sheffield
country: United Kingdom
facility: Local Institution - 964
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: