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

Multiple Sclerosis Clinical Trial

Official title:

A Phase 3 Open Label Study to Evaluate the Long-term Safety and Tolerability of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02634307
• Other study ID #: ALK8700-A301
• Secondary ID: 2015-005160-41
• Status: Completed
• Phase: Phase 3
• Start date: December 10, 2015
• Est. completion date: November 11, 2021

Study information

• Verified date: July 2022
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1057
• Est. completion date: November 11, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• Has a confirmed diagnosis of RRMS

• Neurologically stable with no evidence of relapse within 30 days prior to Visit 2

Exclusion Criteria:

• 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

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• ALKS 8700
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Belgium	Alkermes Investigational Site	Brugge
Belgium	Alkermes Investigational Site	Fraiture
Belgium	Alkermes Investigational Site	La Louviere
Bulgaria	Alkermes Investigational Site	Blagoevgrad
Bulgaria	Alkermes Investigational Site	Pleven
Bulgaria	Alkermes Investigational Site	Sofia
Bulgaria	Alkermes Investigational Site	Sofia
Bulgaria	Alkermes Investigational Site	Sofia
Canada	Alkermes Investigational Site	Gatineau	Quebec
Germany	Alkermes Investigational Site	Berlin
Germany	Alkermes Investigational Site	Berlin
Germany	Alkermes Investigational Site	Dresden
Germany	Alkermes Investigational Site	Leipzig
Germany	Alkermes Investigational Site	Ulm
Germany	Alkermes Investigational Site	Ulm
Germany	Alkermes Investigational Site	Westerstede
Poland	Alkermes Investigational Site	Gdansk
Poland	Alkermes Investigational Site	Katowice
Poland	Alkermes Investigational Site	Katowice
Poland	Alkermes Investigational Site	Kielce
Poland	Alkermes Investigational Site	Krakow
Poland	Alkermes Investigational Site	Lodz
Poland	Alkermes Investigational Site	Lublin
Poland	Alkermes Investigational Site	Plewiska
Poland	Alkermes Investigational Site	Szczecin
Russian Federation	Alkermes Investigational Site	Krasnoyarsk
Russian Federation	Alkermes Investigational Site	Nizhniy Novgorod
Serbia	Alkermes Investigational Site	Belgrade
Serbia	Alkermes Investigational Site	Kragujevac
Serbia	Alkermes Investigational Site	Nis
Spain	Alkermes Investigational Site	Barcelona
Spain	Alkermes Investigational Site	Madrid
Spain	Alkermes Investigational Site	Santa Cruz de Tenerife
Ukraine	Alkermes Investigational Site	Dnipro
Ukraine	Alkermes Investigational Site	Ivano-Frankivsk
Ukraine	Alkermes Investigational Site	Kharkiv
Ukraine	Alkermes Investigational Site	Kharkiv
Ukraine	Alkermes Investigational Site	Lviv
Ukraine	Alkermes Investigational Site	Odessa
Ukraine	Alkermes Investigational Site	Zaporizhzhya
Ukraine	Alkermes Investigational Site	Zaporizhzhya
United States	Alkermes Investigational Site	Albuquerque	New Mexico
United States	Alkermes Investigational Site	Alexandria	Louisiana
United States	Alkermes Investigational Site	Atlanta	Georgia
United States	Alkermes Investigational Site	Atlanta	Georgia
United States	Alkermes Investigational Site	Atlanta	Georgia
United States	Alkermes Investigational Site	Atlantis	Florida
United States	Alkermes Investigational Site	Basalt	Colorado
United States	Alkermes Investigational Site	Baton Rouge	Louisiana
United States	Alkermes Investigational Site	Berkeley	California
United States	Alkermes Investigational Site	Bradenton	Florida
United States	Alkermes Investigational Site	Canton	Ohio
United States	Alkermes Investigational Site	Centennial	Colorado
United States	Alkermes Investigational Site	Charleston	South Carolina
United States	Alkermes Investigational Site	Charlotte	North Carolina
United States	Alkermes Investigational Site	Columbus	Ohio
United States	Alkermes Investigational Site	Columbus	Georgia
United States	Alkermes Investigational Site	Cordova	Tennessee
United States	Alkermes Investigational Site	Cullman	Alabama
United States	Alkermes Investigational Site	Dallas	Texas
United States	Alkermes Investigational Site	Dayton	Ohio
United States	Alkermes Investigational Site	Denver	Colorado
United States	Alkermes Investigational Site	Des Moines	Iowa
United States	Alkermes Investigational Site	Detroit	Michigan
United States	Alkermes Investigational Site	Evanston	Illinois
United States	Alkermes Investigational Site	Franklin	Tennessee
United States	Alkermes Investigational Site	Golden Valley	Minnesota
United States	Alkermes Investigational Site	Greensboro	North Carolina
United States	Alkermes Investigational Site	Greer	South Carolina
United States	Alkermes Investigational Site	Houston	Texas
United States	Alkermes Investigational Site	Houston	Texas
United States	Alkermes Investigational Site	Indianapolis	Indiana
United States	Alkermes Investigational Site	Indianapolis	Indiana
United States	Alkermes Investigational Site	Jacksonville	Florida
United States	Alkermes Investigational Site	Knoxville	Tennessee
United States	Alkermes Investigational Site	Lexington	Kentucky
United States	Alkermes Investigational Site	Loma Linda	California
United States	Alkermes Investigational Site	Long Beach	California
United States	Alkermes Investigational Site	Lubbock	Texas
United States	Alkermes Investigational Site	Maitland	Florida
United States	Alkermes Investigational Site	Medford	Oregon
United States	Alkermes Investigational Site	Middlebury	Connecticut
United States	Alkermes Investigational Site	Naples	Florida
United States	Alkermes Investigational Site	Newport News	Virginia
United States	Alkermes Investigational Site	Oklahoma City	Oklahoma
United States	Alkermes Investigational Site	Ormond Beach	Florida
United States	Alkermes Investigational Site	Overland Park	Kansas
United States	Alkermes Investigational Site	Patchogue	New York
United States	Alkermes Investigational Site	Philadelphia	Pennsylvania
United States	Alkermes Investigational Site	Phoenix	Arizona
United States	Alkermes Investigational Site	Phoenix	Arizona
United States	Alkermes Investigational Site	Phoenix	Arizona
United States	Alkermes Investigational Site	Plainview	New York
United States	Alkermes Investigational Site	Raleigh	North Carolina
United States	Alkermes Investigational Site	Richmond	Virginia
United States	Alkermes Investigational Site	Rock Hill	South Carolina
United States	Alkermes Investigational Site	Saint Louis	Missouri
United States	Alkermes Investigational Site	Saint Louis	Missouri
United States	Alkermes Investigational Site	Saint Louis	Missouri
United States	Alkermes Investigational Site	Salt Lake City	Utah
United States	Alkermes Investigational Site	San Diego	California
United States	Alkermes Investigational Site	Sarasota	Florida
United States	Alkermes Investigational Site	Seattle	Washington
United States	Alkermes Investigational Site	Seattle	Washington
United States	Alkermes Investigational Site	Seattle	Washington
United States	Alkermes Investigational Site	Spartanburg	South Carolina
United States	Alkermes Investigational Site	Stamford	Connecticut
United States	Alkermes Investigational Site	Stony Brook	New York
United States	Alkermes Investigational Site	Syracuse	New York
United States	Alkermes Investigational Site	Tampa	Florida
United States	Alkermes Investigational Site	Traverse City	Michigan
United States	Alkermes Investigational Site	Tucson	Arizona
United States	Alkermes Investigational Site	Vero Beach	Florida
United States	Alkermes Investigational Site	Washington	District of Columbia
United States	Alkermes Investigational Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Biogen	Alkermes, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Germany,  Poland,  Russian Federation,  Serbia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Annualized Relapse Rate (ARR)	Relapse was defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, accompanied by one or more of the following: New objective neurological findings upon examination by the treating neurologist that are functionally consistent with findings on the Expanded Disability Status Scale [EDSS] (performed within 7 days of onset of symptoms) with an increase over the prior visit of = 0.5 for the total score, an increase of = 2 in 1 functional system (FS), except bladder/cognitive changes, and/or, an increase of = 1 in 2 FS, except bladder/cognitive changes. The relapse rate for an individual participant was calculated as the number of relapses for that participant divided by the number of participant-years followed. The ARR for each enrollment group was calculated as the total number of relapses experienced in the group divided by the total number of participant-years on study.	Up to 96 weeks
Other	Percentage of Participants With Multiple Sclerosis (MS) Relapse	Relapse was defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, accompanied by one or more of the following: New objective neurological findings upon examination by the treating neurologist that are functionally consistent with findings on the EDSS (performed within 7 days of onset of symptoms) with an increase over the prior visit of = 0.5 for the total score, an increase of = 2 in 1 FS, except bladder/cognitive changes, and/or, an increase of = 1 in 2 FS, except bladder/cognitive changes.	Up to 96 weeks
Other	Change From Baseline in Expanded Disability Status Scale (EDSS) Score	The EDSS is used to measure and evaluate MS participants' level of functioning. The EDSS provides a total score on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic examination; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. Higher scores indicate more disability. Positive change from baseline indicates more disability.	Baseline up to Week 96
Other	Change From Baseline in Timed 25-Foot Walk Test (T25-FW) Score	The T25-FW is a reliable quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant was directed to one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly as possible, but safely. Participants were allowed to use assistive devices (canes, crutches, walkers) as needed. The time was calculated from when the lead foot crosses the start point to when the participant had reached the 25-foot mark. The task was immediately administered again by having the participant walk back the same distance. The score for the T25-FW was calculated as the average of the 2 completed trials. A negative change from Baseline indicates improvement.	Baseline up to Week 96
Other	Change From Baseline in the EuroQol 5-Dimension 5-Level Visual Analog Scale (EQ-5D-5L VAS) Score	The EQ-5D-5L is an instrument designed to assess decrements in health. The EQ-5D-5L includes a VAS and a descriptive system that defines health in terms of 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response categories corresponding to the level of severity (i.e., no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale numbered from 100 (best health imagined) to 0 (worst health imagined). Higher scores indicate good health. Positive change from baseline indicates improved health.	Baseline up to Week 96
Other	Change From Baseline in the EQ-5D-5L Index Score	The EQ-5D-5L is an instrument designed to assess decrements in health. The EQ-5D-5L includes a VAS and a descriptive system that defines health in terms of 5 dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each dimension has 5 response categories corresponding to the level of severity (i.e., no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). Higher scores indicate good health. Positive change from baseline indicates improved health.	Baseline up to Week 96
Other	Change From Baseline in the 12-item Short Form Health Survey (SF-12) Score	The SF-12 uses 12 questions to measure functional health and well-being from the study participant's perspective across eight domains: physical functioning, role, bodily pain, general health perceptions, vitality, social functioning, emotional role, and mental health. Mental and physical composite scores (MCS & PCS) are computed using the scores of twelve questions and range from 0 to 100, where a higher score indicates better health. Positive change from baseline indicates improved health.	Baseline up to Week 96
Other	Time to Onset of 12-week Confirmed Disability Progression	The time to onset of 12-week confirmed disability progression is defined as the time from baseline to the first disability progression that is confirmed at the next regularly scheduled visit = 12 weeks after the initial disability progression. Disability progression is defined by one of the following: an EDSS increase of at least 1.5 points from baseline EDSS = 0, an EDSS increase of at least a 1.0 point from baseline EDSS between 1.0 and 5.5 (inclusive), or an EDSS increase of at least 0.5 points from baseline EDSS = 6.0.	Up to Week 96
Other	Percentage of Participants With No Evidence of Disease Activity (NEDA) at Week 96	The definition of NEDA-3 encompasses a combination of the following 3 related measures of disease activity: No relapses, no confirmed disability progression sustained for 12 weeks as measured on EDSS, and no magnetic resonance imaging (MRI) disease activity, defined as no gadolinium-enhancing (GdE) lesions and no new or enlarging T2 lesions. The definition of NEDA-4 was the above definition of NEDA-3 with the addition of a mean annualized rate of brain volume loss of less than 0.4% where annualized rate of brain volume loss was derived from percentage brain volume change (PBVC) from baseline and was calculated as ([PBVC/100+1]^[365.25/days]-1) × 100.	Week 96
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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)