Clinical trial NCT03093324: A Tolerability Study of ALKS 8700 in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) EVOLVE-MS-2
Official title: A Phase 3 Study in Subjects With Relapsing Remitting Multiple Sclerosis to Evaluate the Tolerability of ALKS 8700 and Dimethyl Fumarate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: RRMS
Multiple Sclerosis
MS
Alkermes
ALKS 8700
Dimethyl Fumarate
DMF
Tecfidera
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Alkermes, Inc.
First posted: 2017-03-28
Enrollment: 506
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to evaluate the utility of two gastrointestinal (GI) symptom scales (Individual GI Symptom and Impact Scale {IGISIS} and Global GI Symptom and Impact Scale {GGISIS}) in assessing GI tolerability in adult subjects with RRMS after administration of ALKS 8700 or Dimethyl Fumarate (DMF) in Part A, to compare the GI tolerability of ALKS 8700 and DMF in adult subjects with RRMS using IGISIS and GGISIS in Part B, and to Evaluate the safety and tolerability of ALKS 8700 in adult subjects with RRMS in Parts A and B.


Eligibility criteria: Key Inclusion Criteria:

* Capable of understanding and complying with the protocol
* Has a confirmed diagnosis of RRMS
* Neurologically stable with no evidence of relapse within 30 days prior to randomization
* Agrees to use an acceptable method of contraception for the duration of the study and for 30 days after any study drug administration, or is surgically sterile or post-menopausal

Key Exclusion Criteria:

* Have any finding(s) that would compromise the safety of the subject, affect the subject's ability to adhere to the protocol visit schedule or to fulfill visit requirements, or would make the subject unsuitable for participation in the study
* Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
* History of clinically significant cardiovascular, pulmonary, GI, dermatologic, psychiatric, neurologic (other than MS), endocrine, renal, and/or other major disease that would preclude participation in a clinical trial
* History of GI surgery (except appendectomy that occurred more than 6 months prior to screening
* History of clinically significant recurring or active gastrointestinal symptoms (eg, nausea, diarrhea, dyspepsia, constipation) within 3 months of screening
* Chronic use (7 days) of medical therapy to treat any GI symptoms within 1 month of screening Has a clinically significant medical condition or observed abnormality at screening
* History of a myocardial infarction, including a silent myocardial infarction or unstable angina
* History of clinically significant drug or alcohol abuse within the past year prior to screening
* Clinically significant history of suicidal ideation or suicidal behavior in the last 12 months
* Subject is pregnant or breastfeeding or plans to become pregnant or begin breastfeeding at any point during the study and for 30 days after any study drug administration
* Prior use of Dimethyl Fumarate (DMF)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Days With Any Individual Gastrointestinal Symptom and Impact Scale (IGISIS) Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
Secondary outcomes:
measure: Number of Days With Any IGISIS Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Part B
timeFrame: End of treatment (up to Week 6) for Part B
measure: Number of Days With Any IGISIS Individual Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
measure: Number of Days With Any IGISIS Individual Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
measure: Number of Days With a Global GI Symptom and Impact Scale (GGISIS) Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
measure: Number of Days With a GGISIS Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
measure: Number of Days With a GGISIS Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
measure: Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B
timeFrame: End of treatment (up to Week 6) for both Parts A and B
measure: Number of Participants With Adverse Events (AEs)
timeFrame: End of study (up to Week 10)
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Alkermes Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: Alkermes Investigational Site
state: Arizona
city: Tucson
country: United States
facility: Alkermes Investigational Site
state: Arizona
city: Long Beach
country: United States
facility: Alkermes Investigational Site
state: California
city: San Diego
country: United States
facility: Alkermes Investigational Site
state: California
city: Basalt
country: United States
facility: Alkermes Investigational Site
state: Colorado
city: Centennial
country: United States
facility: Alkermes Investigational Site
state: Colorado
city: Denver
country: United States
facility: Alkermes Investigational Site
state: Colorado
city: Middlebury
country: United States
facility: Alkermes Investigational Site
state: Connecticut
city: Stamford
country: United States
facility: Alkermes Investigational Site
state: Connecticut
city: Washington
country: United States
facility: Alkermes Investigational Site
state: District of Columbia
city: Atlantis
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Bradenton
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Maitland
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Naples
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Ormond Beach
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Sarasota
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Tampa
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: Alkermes Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Alkermes Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Alkermes Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Alkermes Investigational Site
state: Georgia
city: Columbus
country: United States
facility: Alkermes Investigational Site
state: Georgia
city: Evanston
country: United States
facility: Alkermes Investigational Site
state: Illinois
city: Des Moines
country: United States
facility: Alkermes Investigational Site
state: Iowa
city: Lenexa
country: United States
facility: Alkermes Investigational Site
state: Kansas
city: Alexandria
country: United States
facility: Alkermes Investigational Site
state: Louisiana
city: Detroit
country: United States
facility: Alkermes Investigational Site
state: Michigan
city: Golden Valley
country: United States
facility: Alkermes Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: Alkermes Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Alkermes Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Alkermes Investigational Site
state: Missouri
city: Albuquerque
country: United States
facility: Alkermes Investigational Site
state: New Mexico
city: Patchogue
country: United States
facility: Alkermes Investigational Site
state: New York
city: Stony Brook
country: United States
facility: Alkermes Investigational Site
state: New York
city: Syracuse
country: United States
facility: Alkermes Investigational Site
state: New York
city: Charlotte
country: United States
facility: Alkermes Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: Alkermes Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Alkermes Investigational Site
state: North Carolina
city: Canton
country: United States
facility: Alkermes Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Alkermes Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Alkermes Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Alkermes Investigational Site
state: Oklahoma
city: Charleston
country: United States
facility: Alkermes Investigational Site
state: South Carolina
city: Greer
country: United States
facility: Alkermes Investigational Site
state: South Carolina
city: Indian Land
country: United States
facility: Alkermes Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Alkermes Investigational Site
state: South Carolina
city: Franklin
country: United States
facility: Alkermes Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: Alkermes Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Alkermes Investigational Site
state: Texas
city: Houston
country: United States
facility: Alkermes Investigational Site
state: Texas
city: Houston
country: United States
facility: Alkermes Investigational Site
state: Texas
city: Newport News
country: United States
facility: Alkermes Investigational Site
state: Virginia
city: Richmond
country: United States
facility: Alkermes Investigational Site
state: Virginia
city: Seattle
country: United States
facility: Alkermes Investigational Site
state: Washington
city: Seattle
country: United States
facility: Alkermes Investigational Site
state: Washington
city: Seattle
country: United States
facility: Alkermes Investigational Site
state: Washington
city: Dresden
country: Germany
facility: Alkermes Investigational Site
city: Leipzig
country: Germany
facility: Alkermes Investigational Site
city: Ulm
country: Germany
facility: Alkermes Investigational Site
city: Westerstede
country: Germany
facility: Alkermes Investigational Site
city: Gdańsk
country: Poland
facility: Alkermes Investigational Site
city: Katowice
country: Poland
facility: Alkermes Investigational Site
city: Kielce
country: Poland
facility: Alkermes Investigational Site
city: Lodz
country: Poland
facility: Alkermes Investigational Site
city: Plewiska
country: Poland
facility: Alkermes Investigational Site
city: Szczecin
country: Poland
facility: Alkermes Investigational Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Wundes A, Wray S, Gold R, Singer BA, Jasinska E, Ziemssen T, de Seze J, Repovic P, Chen H, Hanna J, Messer J, Miller C, Naismith RT. Improved gastrointestinal profile with diroximel fumarate is associated with a positive impact on quality of life compared with dimethyl fumarate: results from the randomized, double-blind, phase III EVOLVE-MS-2 study. Ther Adv Neurol Disord. 2021 Mar 19;14:1756286421993999. doi: 10.1177/1756286421993999. eCollection 2021.
citation: Naismith RT, Wundes A, Ziemssen T, Jasinska E, Freedman MS, Lembo AJ, Selmaj K, Bidollari I, Chen H, Hanna J, Leigh-Pemberton R, Lopez-Bresnahan M, Lyons J, Miller C, Rezendes D, Wolinsky JS; EVOLVE-MS-2 Study Group. Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study. CNS Drugs. 2020 Feb;34(2):185-196. doi: 10.1007/s40263-020-00700-0.