A Tolerability Study of ALKS 8700 in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) EVOLVE-MS-2

A Phase 3 Study in Subjects With Relapsing Remitting Multiple Sclerosis to Evaluate the Tolerability of ALKS 8700 and Dimethyl Fumarate

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.

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Dimethyl Fumarate; Drug: ALKS 8700

• Study Type: Interventional
• Enrollment (Actual): 506
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany
    • Alkermes Investigational Site
  • Leipzig, Germany
    • Alkermes Investigational Site
  • Ulm, Germany
    • Alkermes Investigational Site
  • Westerstede, Germany
    • Alkermes Investigational Site
• Poland
  • Gdańsk, Poland, 80-803
    • Alkermes Investigational Site
  • Katowice, Poland, 40-123
    • Alkermes Investigational Site
  • Kielce, Poland, 25-726
    • Alkermes Investigational Site
  • Lodz, Poland, 90-324
    • Alkermes Investigational Site
  • Plewiska, Poland, 62-064
    • Alkermes Investigational Site
  • Szczecin, Poland, 70-111
    • Alkermes Investigational Site
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • Alkermes Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Alkermes Investigational Site
    • Tucson, Arizona, United States, 85704
      • Alkermes Investigational Site
  • California
    • Long Beach, California, United States, 90806
      • Alkermes Investigational Site
    • San Diego, California, United States, 92103
      • Alkermes Investigational Site
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Alkermes Investigational Site
    • Centennial, Colorado, United States, 80112
      • Alkermes Investigational Site
    • Denver, Colorado, United States, 80209
      • Alkermes Investigational Site
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Alkermes Investigational Site
    • Stamford, Connecticut, United States, 06905
      • Alkermes Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Alkermes Investigational Site
  • Florida
    • Atlantis, Florida, United States, 33462
      • Alkermes Investigational Site
    • Bradenton, Florida, United States, 34209
      • Alkermes Investigational Site
    • Maitland, Florida, United States, 32751
      • Alkermes Investigational Site
    • Naples, Florida, United States, 34105
      • Alkermes Investigational Site
    • Ormond Beach, Florida, United States, 32174
      • Alkermes Investigational Site
    • Sarasota, Florida, United States, 34233
      • Alkermes Investigational Site
    • Tampa, Florida, United States, 33634
      • Alkermes Investigational Site
    • Vero Beach, Florida, United States, 32960
      • Alkermes Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • Alkermes Investigational Site
    • Atlanta, Georgia, United States, 30327
      • Alkermes Investigational Site
    • Atlanta, Georgia, United States, 30342
      • Alkermes Investigational Site
    • Columbus, Georgia, United States, 31904
      • Alkermes Investigational Site
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Alkermes Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Alkermes Investigational Site
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • Alkermes Investigational Site
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Alkermes Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Alkermes Investigational Site
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Alkermes Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Alkermes Investigational Site
    • Saint Louis, Missouri, United States, 63104
      • Alkermes Investigational Site
    • Saint Louis, Missouri, United States, 63131
      • Alkermes Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Alkermes Investigational Site
  • New York
    • Patchogue, New York, United States, 11772
      • Alkermes Investigational Site
    • Stony Brook, New York, United States, 11794
      • Alkermes Investigational Site
    • Syracuse, New York, United States, 13210
      • Alkermes Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Alkermes Investigational Site
    • Greensboro, North Carolina, United States, 27405
      • Alkermes Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Alkermes Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Alkermes Investigational Site
    • Columbus, Ohio, United States, 43221
      • Alkermes Investigational Site
    • Dayton, Ohio, United States, 45417
      • Alkermes Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Alkermes Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Alkermes Investigational Site
    • Greer, South Carolina, United States, 29650
      • Alkermes Investigational Site
    • Indian Land, South Carolina, United States, 29707
      • Alkermes Investigational Site
    • Spartanburg, South Carolina, United States, 29307
      • Alkermes Investigational Site
  • Tennessee
    • Franklin, Tennessee, United States, 37064
      • Alkermes Investigational Site
    • Knoxville, Tennessee, United States, 37922
      • Alkermes Investigational Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Alkermes Investigational Site
    • Houston, Texas, United States, 77030
      • Alkermes Investigational Site
    • Houston, Texas, United States, 77074
      • Alkermes Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23601
      • Alkermes Investigational Site
    • Richmond, Virginia, United States, 23226
      • Alkermes Investigational Site
  • Washington
    • Seattle, Washington, United States, 98101
      • Alkermes Investigational Site
    • Seattle, Washington, United States, 98122
      • Alkermes Investigational Site
    • Seattle, Washington, United States, 98133
      • Alkermes Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ALKS 8700; Oral capsules, administered orally twice daily.	Drug: ALKS 8700; Administered as specified in the treatment arm.
ACTIVE_COMPARATOR: Dimethyl Fumarate; Oral capsules, administered orally twice daily.	Drug: Dimethyl Fumarate; Administered as specified in the treatment arm.; Other Names: Tecfidera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for both Parts A and B

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days With Any IGISIS Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Part B	IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for Part B
Number of Days With Any IGISIS Individual Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B	IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for both Parts A and B
Number of Days With Any IGISIS Individual Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B	IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for both Parts A and B
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	GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for both Parts A and B
Number of Days With a GGISIS Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B	GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for both Parts A and B
Number of Days With a GGISIS Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B	GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries.	End of treatment (up to Week 6) for both Parts A and B
Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B	IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries. Scores were averaged for 5-week treatment period.	End of treatment (up to Week 6) for both Parts A and B
Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	End of study (up to Week 10)

Collaborators and Investigators

• Sponsor: Biogen
• Collaborators: Alkermes, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 15, 2017
• Primary Completion (ACTUAL): June 27, 2019
• Study Completion (ACTUAL): June 27, 2019

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (ACTUAL): March 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; RRMS; MS; Alkermes; Dimethyl Fumarate; Tecfidera; ALKS 8700; DMF
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: ALK8700-A302; 2017-001294-16 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No