A Study of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis (MS) EVOLVE-MS-1

NCT02634307 | Completed Phase 3 Results

• 2 other identifiers: ALK8700-A3012015-005160-41
• Study Type: interventional
• Target: 1,057
• Locations: 10 countries
• Sites: 115

Brief Summary

The primary objective of this study is to evaluate the long-term safety and tolerability of ALKS 8700 for the treatment of Relapsing Remitting Multiple Sclerosis (RRMS). The secondary objective of this study is to evaluate treatment effect over time in adult participants with RRMS treated with ALKS 8700.

Conditions

Multiple Sclerosis

Keywords

MS; Relapsing Remitting Multiple Sclerosis; RRMS; dimethyl fumarate; DMF

Outcome Measures

Primary Outcomes (5)

• Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  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 assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is any AE that start or worsen on or after the date of first dose of study treatment. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.

  From first dose to two weeks after last dose of study drug (Up to 98 weeks)

• Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities

  Vital sign measurements included heart rate (low: \<=50 beats per minute \[bpm\] and decrease \>=15 bpm; High: \>=120 bpm and increase \>=15 bpm), systolic blood pressure (BP) (low: \<=90 millimeters of mercury \[mmHg\] and decrease \>=20 mmHg; High: \>=180 mmHg and increase \>=20 mmHg) and diastolic BP (low: \<=50 mmHg and decrease \>=15 mmHg; High: \>=105 mmHg and increase \>=15 mmHg).

  From first dose to two weeks after last dose of study drug (Up to 98 weeks)

• Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

  Potentially clinically significant QTcF values (\>450 to \<=480 millisecond \[msec\], \>480 to \<=500 msec) at any post-baseline visit during treatment period were reported.

  From first dose to two weeks after last dose of study drug (Up to 98 weeks)

• Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit

  The C-SSRS is a clinician-administered instrument that systematically assess suicidal ideation and behavior rating scale. It rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). The scale identifies specific behaviors ranging from "preparatory acts or behavior" to "suicide" which may be indicative of an individual's intent to complete suicide.

  Up to 98 weeks

• Number of Participants With Potentially Clinically Significant Laboratory Abnormalities

  Laboratory assessments included hematology, biochemistry, and urinalysis. Abnormality criteria: \>=3xupper limit of normal (ULN) in alanine aminotransferase, aspartate aminotransferase; In millimoles per liter (mmol/L) \[bicarbonate\<15/\>31, chloride\<=90, potassium\<3/\>5.5, sodium\<130/\>150\]; In mg per decilitre(mg/dL) {total bilirubin\>=2.0, calcium\<8.2/\>12, total cholesterol\>300, creatinine\>=2.0, glucose\<50/\>200, cholesterol: High density lipoprotein (HDL)\<=30, low density lipoprotein (LDL)\>=160, triglycerides\>=120 \[female(F)\]/\>=160 \[male(M)\], urate\>9/\>8(F), blood urea nitrogen\>30}; \>3xULN in creatine kinase, lactate dehydrogenase; Hematocrit \<=32(F)/\<=37(M) percentage(%),3 point decrease from baseline; Hemoglobin\<=9.5(F)/\<=11.5(M)g/dL; Lymphocytes\<0.5x10\^9/L; In 10\^3/microliter(uL) \[Eosinophils\>1; Absolute neutrophils\<1.5; Platelets\<75.1/\>=700; Leukocytes\<=2.8/\>=16\]; Albumin/creatinine\>200g/kilograms(kg); Beta-2 microglobulin \>0.3milligrams/liter(mg/L); Glucose/protein at least 2+.

  From first dose to two weeks after last dose of study drug (Up to 98 weeks)

Other Outcomes (9)

• Annualized Relapse Rate (ARR)

  Up to 96 weeks

• Percentage of Participants With Multiple Sclerosis (MS) Relapse

  Up to 96 weeks

• Change From Baseline in Expanded Disability Status Scale (EDSS) Score

  Baseline up to Week 96

Study Arms (1)

ALKS 8700

EXPERIMENTAL

Oral capsules taken twice daily.

Drug: ALKS 8700

Interventions

ALKS 8700 DRUG

Administered as specified in the treatment arm.

ALKS 8700

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a confirmed diagnosis of RRMS
• Neurologically stable with no evidence of relapse within 30 days prior to Visit 2

You may not qualify if:

• 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
• Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
• History of clinically significant cardiovascular, pulmonary, gastrointestinal, dermatologic, psychiatric, neurologic (other than MS), and/or other major disease that would preclude participation in a clinical trial
• History of a myocardial infarction, including a silent myocardial infarction identified on ECG, or unstable angina

Sponsors & Collaborators

• Biogen: lead
• Alkermes, Inc.: collaborator

Study Sites (115)

Alkermes Investigational Site

Cullman, Alabama, 35058, United States

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Alkermes Investigational Site

Phoenix, Arizona, 85004, United States

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Phoenix, Arizona, 85018, United States

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Phoenix, Arizona, 85032, United States

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Tucson, Arizona, 85704, United States

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Berkeley, California, 94705, United States

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Loma Linda, California, 92354, United States

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Long Beach, California, 90806, United States

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San Diego, California, 92103, United States

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Basalt, Colorado, 81621, United States

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Alkermes Investigational Site

Centennial, Colorado, 80111, United States

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Denver, Colorado, 80209, United States

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Middlebury, Connecticut, 06762, United States

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Stamford, Connecticut, 06905, United States

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Washington D.C., District of Columbia, 20007, United States

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Atlantis, Florida, 33462, United States

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Bradenton, Florida, 34209, United States

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Jacksonville, Florida, 32209, United States

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Maitland, Florida, 32751, United States

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Naples, Florida, 34102, United States

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Ormond Beach, Florida, 32174, United States

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Sarasota, Florida, 34239, United States

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Tampa, Florida, 33634, United States

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Vero Beach, Florida, 32960, United States

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Atlanta, Georgia, 30312-4201, United States

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Atlanta, Georgia, 30327, United States

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Atlanta, Georgia, 30342, United States

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Columbus, Georgia, 31904, United States

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Evanston, Illinois, 60201, United States

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Indianapolis, Indiana, 46202, United States

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Indianapolis, Indiana, 46260, United States

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Des Moines, Iowa, 50314, United States

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Overland Park, Kansas, 66213, United States

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Lexington, Kentucky, 40513, United States

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Alexandria, Louisiana, 71301, United States

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Baton Rouge, Louisiana, 70810, United States

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Detroit, Michigan, 48202, United States

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Traverse City, Michigan, 49684, United States

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Golden Valley, Minnesota, 55422, United States

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St Louis, Missouri, 63104, United States

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St Louis, Missouri, 63110, United States

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St Louis, Missouri, 63131, United States

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Albuquerque, New Mexico, 87106, United States

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Patchogue, New York, 11772, United States

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Plainview, New York, 11803, United States

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Stony Brook, New York, 11794, United States

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Syracuse, New York, 13210, United States

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Charlotte, North Carolina, 28203, United States

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Greensboro, North Carolina, 27405, United States

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Raleigh, North Carolina, 27607, United States

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Winston-Salem, North Carolina, 27103, United States

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Canton, Ohio, 44718, United States

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Columbus, Ohio, 43210, United States

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Dayton, Ohio, 45417, United States

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Oklahoma City, Oklahoma, 73104, United States

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Medford, Oregon, 97504, United States

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Philadelphia, Pennsylvania, 19107, United States

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Charleston, South Carolina, 29406, United States

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Greer, South Carolina, 29650, United States

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Rock Hill, South Carolina, 29732, United States

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Spartanburg, South Carolina, 29307, United States

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Cordova, Tennessee, 38018, United States

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Franklin, Tennessee, 37064, United States

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Knoxville, Tennessee, 37922, United States

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Dallas, Texas, 75231, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77074, United States

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Lubbock, Texas, 79410, United States

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Salt Lake City, Utah, 84103, United States

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Newport News, Virginia, 23601, United States

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Richmond, Virginia, 23228, United States

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Seattle, Washington, 98101, United States

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Seattle, Washington, 98122, United States

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Seattle, Washington, 98133, United States

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Alkermes Investigational Site

Bruges, 8000, Belgium

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Fraiture, 4557, Belgium

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La Louvière, 7100, Belgium

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Blagoevgrad, 2700, Bulgaria

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Pleven, 5800, Bulgaria

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Sofia, 1309, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1797, Bulgaria

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Gatineau, Quebec, J8Y 1W2, Canada

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Berlin, 10713, Germany

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Berlin, 12099, Germany

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Dresden, 01307, Germany

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Leipzig, 4103, Germany

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Ulm, 89073, Germany

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Ulm, 89081, Germany

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Westerstede, 26655, Germany

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Gdansk, 80-803, Poland

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Katowice, 40-123, Poland

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Katowice, 40-648, Poland

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Kielce, 25-726, Poland

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Krakow, 31-505, Poland

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Lodz, 90-324, Poland

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Lublin, 20-718, Poland

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Plewiska, 62-064, Poland

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Szczecin, 70-111, Poland

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Krasnoyarsk, 66037, Russia

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Nizhny Novgorod, 603155, Russia

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Belgrade, 11000, Serbia

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Kragujevac, 34000, Serbia

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Niš, 18000, Serbia

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Barcelona, 08916, Spain

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Madrid, 28905, Spain

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Santa Cruz de Tenerife, 38010, Spain

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Dnipro, 49005, Ukraine

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Ivano-Frankivsk, 76008, Ukraine

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Kharkiv, 61068, Ukraine

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Kharkiv, 61103, Ukraine

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Lviv, 79000, Ukraine

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Odesa, 65025, Ukraine

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Zaporizhzhya, 69035, Ukraine

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Zaporizhzhya, 69600, Ukraine

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Related Publications (6)

• Singer BA, Wray S, Gudesblatt M, Bumstead B, Ziemssen T, Bonnell A, Scaramozza M, Levin S, Shanmugasundaram M, Chen H, Mendoza JP, Lewin JB, Shankar SL. Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing-Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study. Neurol Ther. 2024 Aug;13(4):1273-1285. doi: 10.1007/s40120-024-00637-2. Epub 2024 Jun 27.

  PMID: 38935202 DERIVED

• Bowen JD, Stulc J, Hunter SF, Chen H, Lewin JB, Scaramozza M, Bozin I, Then Bergh F. Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study. Adv Ther. 2024 Aug;41(8):3396-3406. doi: 10.1007/s12325-024-02901-1. Epub 2024 Jun 15.

  PMID: 38878121 DERIVED

• Jiang T, Ziemssen T, Wray S, Shen C, Soderbarg K, Lewin JB, Bozin I, Freedman MS. Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis. CNS Drugs. 2023 May;37(5):441-452. doi: 10.1007/s40263-023-01002-x. Epub 2023 May 8.

  PMID: 37155132 DERIVED

• Wray S, Then Bergh F, Wundes A, Arnold DL, Drulovic J, Jasinska E, Bowen JD, Negroski D, Naismith RT, Hunter SF, Gudesblatt M, Chen H, Lyons J, Shankar SL, Kapadia S, Mendoza JP, Singer BA. Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study. Adv Ther. 2022 Apr;39(4):1810-1831. doi: 10.1007/s12325-022-02068-7. Epub 2022 Feb 24.

  PMID: 35211872 DERIVED

• Naismith RT, Wolinsky JS, Wundes A, LaGanke C, Arnold DL, Obradovic D, Freedman MS, Gudesblatt M, Ziemssen T, Kandinov B, Bidollari I, Lopez-Bresnahan M, Nangia N, Rezendes D, Yang L, Chen H, Liu S, Hanna J, Miller C, Leigh-Pemberton R. Diroximel fumarate (DRF) in patients with relapsing-remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study. Mult Scler. 2020 Nov;26(13):1729-1739. doi: 10.1177/1352458519881761. Epub 2019 Nov 4.

  PMID: 31680631 DERIVED

• Palte MJ, Wehr A, Tawa M, Perkin K, Leigh-Pemberton R, Hanna J, Miller C, Penner N. Improving the Gastrointestinal Tolerability of Fumaric Acid Esters: Early Findings on Gastrointestinal Events with Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis from the Phase 3, Open-Label EVOLVE-MS-1 Study. Adv Ther. 2019 Nov;36(11):3154-3165. doi: 10.1007/s12325-019-01085-3. Epub 2019 Sep 19.

  PMID: 31538304 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 18, 2015
• Study Start: December 10, 2015
• Primary Completion: June 1, 2021
• Study Completion: November 11, 2021
• Last Updated: July 26, 2022
• Results First Posted: June 24, 2022

Record last verified: 2022-07

Locations

BU (5); US (74); RU (2); DE (7); CA (1); PL (9); ES (3); UA (8); SE (3); BE (3)