Clinical trial NCT02638103: Efficacy and Safety of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine
Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group Study Evaluating the Long-Term Safety, Tolerability, and Efficacy of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 1890
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study to evaluate the long-term safety, tolerability, and efficacy of subcutaneous (SC) administration of TEV-48125 in adult participants with chronic migraine (CM) or episodic migraine (EM). Participants with CM or EM who complete the pivotal efficacy studies of TEV-48125 (TV48125-CNS-30049 \[NCT02621931\] and TV48125-CNS-30050 \[NCT02629861\]) and agree to participate in this study; and new participants meeting eligibility criteria (not rolling over from pivotal studies), will be enrolled in this study.


Eligibility criteria: Inclusion Criteria:

Participants Rolling Over from the Pivotal Efficacy Studies:

* Participant must have signed and dated the informed consent document.
* Participant must have completed the pivotal efficacy study without major protocol violations.

  * Additional criteria apply, please contact the investigator for more information.

Participants Not Rolling Over from the Pivotal Efficacy Studies:

* Males or females aged 18 to 70 years, inclusive, with migraine onset at less than or equal to (≤) 50 years of age.
* Participant signed and dated the informed consent document.
* Participant has a history of migraine or clinical judgment suggests a migraine diagnosis.
* Participant fulfills the criteria for EM or CM with prospectively collected baseline information during the 28-day run-in period.
* Body mass index (BMI) of 17.5 to 37.5 kilograms/square meter (kg/m\^2) and a total body weight between 45 and 120 kg, inclusive.
* All participants must be of non-childbearing potential.

  1. Participants must simultaneously use 2 forms of highly effective contraception methods.
  2. Participants will remain abstinent throughout the study.
* Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test prior at screening (confirmed by urine dipstick β-HCG pregnancy test at baseline).
* The participant must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the follow-up evaluation.

  * Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

Participants Rolling Over from the Pivotal Efficacy Studies:

* Pregnant or nursing females
* Compliance with daily diary entry lower than 75 percent (%) at the last month of the double-blind treatment period of the pivotal efficacy study.

  * Additional criteria apply, please contact the investigator for more information.

Participants Not Rolling Over from the Pivotal Efficacy Studies:

* Clinically significant findings at the discretion of the investigator.
* Evidence or medical history of clinically significant psychiatric issues, including any suicide attempt in the past, or suicidal ideation with a specific plan in the past 2 years.
* History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological \[for example; cerebral ischemia\], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events) such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism -Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
* Past or current history of cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma.
* Pregnant or nursing females.
* History of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
* Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study drug administration or 5 half-lives, whichever is longer.
* History of alcohol or drug abuse during the past 2 years, or alcohol or drug dependence during the past 5 years.
* The participant cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons:

  1. mentally or legally incapacitated or unable to give consent for any reason.
  2. in custody due to an administrative or a legal decision, under guardianship, or institutionalized.
  3. unable to be contacted in case of emergency.
  4. has any other condition, which, in the opinion of the investigator, makes the participant inappropriate for inclusion in the study.
* Participant is a study center or sponsor employee who is directly involved in the study or the relative of such an employee.

  * Additional criteria apply, please contact the investigator for more information.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline (Day 0) up to follow-up visit (Day 533)
measure: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
timeFrame: Baseline (Day 0) up to end of treatment (EOT) visit (Day 336)
measure: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results
timeFrame: Baseline (Day 0) up to EOT visit (Day 336)
measure: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results
timeFrame: Baseline (Day 0) up to EOT visit (Day 336)
measure: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Baseline (Day 0) up to EOT visit (Day 336)
measure: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
timeFrame: Baseline (Day 0), endpoint (Day 336)
measure: Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results
timeFrame: Baseline (Day 0), endpoint (Day 336)
measure: Number of Participants With Injection Site Reactions
timeFrame: Baseline (Day -28 to Day -1), Month 12
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
timeFrame: Baseline (Day -28 to Day -1), Month 12
Secondary outcomes:
Other outcomes:
measure: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12
timeFrame: Baseline (Day -28 to Day -1), Month 12
measure: Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12
timeFrame: Baseline (Day -28 to Day -1), Month 12
measure: Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12
timeFrame: Baseline (Day -28 to Day -1), Month 12
measure: Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period
timeFrame: Baseline (Day -28 to Day -1), Month 12
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 13628
state: Alabama
city: Birmingham
country: United States
facility: Teva Investigational Site 13577
state: Alabama
city: Phoenix
country: United States
facility: Teva Investigational Site 13606
state: Arizona
city: Phoenix
country: United States
facility: Teva Investigational Site 13579
state: Arizona
city: Little Rock
country: United States
facility: Teva Investigational Site 13602
state: Arkansas
city: Encino
country: United States
facility: Teva Investigational Site 13568
state: California
city: Fullerton
country: United States
facility: Teva Investigational Site 13546
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 13540
state: California
city: Redlands
country: United States
facility: Teva Investigational Site 13632
state: California
city: Redondo Beach
country: United States
facility: Teva Investigational Site 13571
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 13573
state: California
city: Santa Monica
country: United States
facility: Teva Investigational Site 13538
state: California
city: Santa Rosa
country: United States
facility: Teva Investigational Site 13594
state: California
city: Walnut Creek
country: United States
facility: Teva Investigational Site 13595
state: California
city: Aurora
country: United States
facility: Teva Investigational Site 13629
state: Colorado
city: Boulder
country: United States
facility: Teva Investigational Site 13557
state: Colorado
city: Colorado Springs
country: United States
facility: Teva Investigational Site 13593
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 13633
state: Colorado
city: Denver
country: United States
facility: Teva Investigational Site 13612
state: Colorado
city: Englewood
country: United States
facility: Teva Investigational Site 13631
state: Colorado
city: East Hartford
country: United States
facility: Teva Investigational Site 13563
state: Connecticut
city: Stamford
country: United States
facility: Teva Investigational Site 13550
state: Connecticut
city: Bradenton
country: United States
facility: Teva Investigational Site 13635
state: Florida
city: Gainesville
country: United States
facility: Teva Investigational Site 13597
state: Florida
city: Hialeah
country: United States
facility: Teva Investigational Site 13607
state: Florida
city: Jacksonville
country: United States
facility: Teva Investigational Site 13559
state: Florida
city: Ocala
country: United States
facility: Teva Investigational Site 13584
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 13587
state: Florida
city: Palm Beach Gardens
country: United States
facility: Teva Investigational Site 13567
state: Florida
city: Pembroke Pines
country: United States
facility: Teva Investigational Site 13553
state: Florida
city: Pinellas Park
country: United States
facility: Teva Investigational Site 13616
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 13620
state: Georgia
city: Atlanta
country: United States
facility: Teva Investigational Site 13537
state: Georgia
city: Boise
country: United States
facility: Teva Investigational Site 13604
state: Idaho
city: Chicago
country: United States
facility: Teva Investigational Site 13585
state: Illinois
city: Chicago
country: United States
facility: Teva Investigational Site 13621
state: Illinois
city: Evanston
country: United States
facility: Teva Investigational Site 13627
state: Illinois
city: Indianapolis
country: United States
facility: Teva Investigational Site 13596
state: Indiana
city: Wichita
country: United States
facility: Teva Investigational Site 13617
state: Kansas
city: Wichita
country: United States
facility: Teva Investigational Site 13598
state: Kansas
city: Louisville
country: United States
facility: Teva Investigational Site 13566
state: Kentucky
city: Metairie
country: United States
facility: Teva Investigational Site 13603
state: Louisiana
city: Pikesville
country: United States
facility: Teva Investigational Site 13582
state: Maryland
city: Boston
country: United States
facility: Teva Investigational Site 13590
state: Massachusetts
city: New Bedford
country: United States
facility: Teva Investigational Site 13589
state: Massachusetts
city: Watertown
country: United States
facility: Teva Investigational Site 13543
state: Massachusetts
city: Ann Arbor
country: United States
facility: Teva Investigational Site 13539
state: Michigan
city: Golden Valley
country: United States
facility: Teva Investigational Site 13542
state: Minnesota
city: Kansas City
country: United States
facility: Teva Investigational Site 13534
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 13619
state: Missouri
city: Springfield
country: United States
facility: Teva Investigational Site 13536
state: Missouri
city: Fremont
country: United States
facility: Teva Investigational Site 13618
state: Nebraska
city: Las Vegas
country: United States
facility: Teva Investigational Site 13605
state: Nevada
city: Lebanon
country: United States
facility: Teva Investigational Site 13578
state: New Hampshire
city: Martinsville
country: United States
facility: Teva Investigational Site 13575
state: New Jersey
city: Princeton
country: United States
facility: Teva Investigational Site 13622
state: New Jersey
city: Albuquerque
country: United States
facility: Teva Investigational Site 13588
state: New Mexico
city: Amherst
country: United States
facility: Teva Investigational Site 13576
state: New York
city: Plainview
country: United States
facility: Teva Investigational Site 13565
state: New York
city: Greensboro
country: United States
facility: Teva Investigational Site 13544
state: North Carolina
city: Greensboro
country: United States
facility: Teva Investigational Site 13574
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 13545
state: North Carolina
city: Akron
country: United States
facility: Teva Investigational Site 13609
state: Ohio
city: Akron
country: United States
facility: Teva Investigational Site 13625
state: Ohio
city: Akron
country: United States
facility: Teva Investigational Site 13634
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 13533
state: Ohio
city: Cincinnati
country: United States
facility: Teva Investigational Site 13624
state: Ohio
city: Cleveland
country: United States
facility: Teva Investigational Site 13569
state: Ohio
city: Columbus
country: United States
facility: Teva Investigational Site 13626
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 13561
state: Oklahoma
city: Eugene
country: United States
facility: Teva Investigational Site 13601
state: Oregon
city: Jenkintown
country: United States
facility: Teva Investigational Site 13591
state: Pennsylvania
city: Philadelphia
country: United States
facility: Teva Investigational Site 13554
state: Pennsylvania
city: Uniontown
country: United States
facility: Teva Investigational Site 13608
state: Pennsylvania
city: Greer
country: United States
facility: Teva Investigational Site 13615
state: South Carolina
city: Mount Pleasant
country: United States
facility: Teva Investigational Site 13556
state: South Carolina
city: Bristol
country: United States
facility: Teva Investigational Site 13560
state: Tennessee
city: Memphis
country: United States
facility: Teva Investigational Site 13551
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 13532
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 13552
state: Tennessee
city: Austin
country: United States
facility: Teva Investigational Site 13541
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 13623
state: Texas
city: Plano
country: United States
facility: Teva Investigational Site 13611
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 13572
state: Texas
city: Murray
country: United States
facility: Teva Investigational Site 13614
state: Utah
city: West Jordan
country: United States
facility: Teva Investigational Site 13581
state: Utah
city: Virginia Beach
country: United States
facility: Teva Investigational Site 13630
state: Virginia
city: Seattle
country: United States
facility: Teva Investigational Site 13564
state: Washington
city: Seattle
country: United States
facility: Teva Investigational Site 13586
state: Washington
city: Morgantown
country: United States
facility: Teva Investigational Site 13600
state: West Virginia
city: Hamilton
country: Canada
facility: Teva Investigational Site 11124
state: Ontario
city: Newmarket
country: Canada
facility: Teva Investigational Site 11122
state: Ontario
city: Calgary
country: Canada
facility: Teva Investigational Site 11120
city: Montreal
country: Canada
facility: Teva Investigational Site 11121
city: Sarnia
country: Canada
facility: Teva Investigational Site 11123
city: Brno
country: Czechia
facility: Teva Investigational Site 54144
city: Kunratice
country: Czechia
facility: Teva Investigational Site 54141
city: Pardubice
country: Czechia
facility: Teva Investigational Site 54145
city: Prague 4
country: Czechia
facility: Teva Investigational Site 54142
city: Praha 3
country: Czechia
facility: Teva Investigational Site 54146
city: Praha
country: Czechia
facility: Teva Investigational Site 54143
city: Helsinki
country: Finland
facility: Teva Investigational Site 40018
city: Helsinki
country: Finland
facility: Teva Investigational Site 40017
city: Turku
country: Finland
facility: Teva Investigational Site 40016
city: Holon
country: Israel
facility: Teva Investigational Site 80096
city: Jerusalem
country: Israel
facility: Teva Investigational Site 80099
city: Nahariya
country: Israel
facility: Teva Investigational Site 80098
city: Netanya
country: Israel
facility: Teva Investigational Site 80097
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 80100
city: Tel Aviv
country: Israel
facility: Teva Investigational Site 80095
city: Chofu-shi
country: Japan
facility: Teva Investigational Site 84072
city: Kagoshima-shi
country: Japan
facility: Teva Investigational Site 84066
city: Kai
country: Japan
facility: Teva Investigational Site 84069
city: Kawasaki
country: Japan
facility: Teva Investigational Site 84073
city: Kyoto
country: Japan
facility: Teva Investigational Site 84067
city: Osaka-shi
country: Japan
facility: Teva Investigational Site 84062
city: Saitama
country: Japan
facility: Teva Investigational Site 84070
city: Sendai-shi
country: Japan
facility: Teva Investigational Site 84061
city: Shinjuku-ku
country: Japan
facility: Teva Investigational Site 84063
city: Shizuoka
country: Japan
facility: Teva Investigational Site 84068
city: Tochigi
country: Japan
facility: Teva Investigational Site 84065
city: Tokyo
country: Japan
facility: Teva Investigational Site 84064
city: Toyonaka
country: Japan
facility: Teva Investigational Site 84071
city: Krakow
country: Poland
facility: Teva Investigational Site 53364
city: Krakow
country: Poland
facility: Teva Investigational Site 53363
city: Lublin
country: Poland
facility: Teva Investigational Site 53366
city: Poznan
country: Poland
facility: Teva Investigational Site 53365
city: Warsaw
country: Poland
facility: Teva Investigational Site 53367
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50399
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50395
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50394
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50400
city: Nizhniy Novgorod
country: Russian Federation
facility: Teva Investigational Site 50398
city: Nizhniy Novgorod
country: Russian Federation
facility: Teva Investigational Site 50396
city: Ufa
country: Russian Federation
facility: Teva Investigational Site 50397
city: Madrid
country: Spain
facility: Teva Investigational Site 31207
city: Pamplona
country: Spain
facility: Teva Investigational Site 31208
city: Valladolid
country: Spain
facility: Teva Investigational Site 31205
city: Zaragoza
country: Spain
facility: Teva Investigational Site 31206
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: Goadsby PJ, Silberstein SD, Yeung PP, Cohen JM, Ning X, Yang R, Dodick DW. Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study. Neurology. 2020 Nov 3;95(18):e2487-e2499. doi: 10.1212/WNL.0000000000010600. Epub 2020 Sep 10.
citation: Buse DC, Gandhi SK, Cohen JM, Ramirez-Campos V, Cloud B, Yang R, Cowan RP. Improvements across a range of patient-reported domains with fremanezumab treatment: results from a patient survey study. J Headache Pain. 2020 Sep 4;21(1):109. doi: 10.1186/s10194-020-01177-4.