Clinical trial NCT03308968: An Efficacy and Safety Study of Fremanezumab in Adults With Migraine
Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study With an Open-Label Period to Evaluate the Efficacy and Safety of Fremanezumab for the Prophylactic Treatment of Migraine in Patients With Inadequate Response to Prior Preventive Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Migraine Prophylaxis
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-13
Enrollment: 838
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: The purpose of this study is to evaluate the efficacy, safety, and tolerability of monthly and quarterly subcutaneous (sc) injections of fremanezumab compared with sc injections of placebo in participants with chronic migraine (CM) or episodic migraine (EM) who have responded inadequately to 2 to 4 classes of prior preventive treatments.

Approximately equal numbers of participants from each subgroup (CM and EM) are randomized in blinded-fashion 1:1:1 into one of 3 treatments for the subgroup - 2 active treatments and 1 placebo treatment- consisting of monthly injections for 3 months (up to Week 12). Then all participants continue into an open-label extension of 3 months (up to Week 24) during which everyone is administered sc injections of fremanezumab.


Eligibility criteria: Inclusion Criteria:

* The participant has a diagnosis of migraine with onset at ≤50 years of age.
* Body weight ≥45 kilograms.
* The participant has a history of migraine for ≥12 months prior to screening.
* Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is; no vasectomy) must use highly effective birth control methods for the duration of the study and the follow-up period and for 6.0 months after discontinuation of investigational medicinal product (IMP)
* Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically \[that is; vasectomy\] or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, acceptable birth control methods for the duration of the study and for 6.0 months after discontinuation of the investigational medicinal product (IMP).

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

Exclusion Criteria:

* At the time of screening visit, participant is receiving any preventive migraine medications, regardless of the medical indication for more than 5 days and expects to continue with these medications.
* Participant has received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 3 months before screening visit.
* The participant has used an intervention/device (for example; scheduled nerve blocks and transcranial magnetic stimulation) for migraine during the 2 months prior to screening.
* The participant uses triptans/ergots as preventive therapies for migraine.
* Participant uses non-steroidal anti-inflammatory drugs (NSAIDs) as preventive therapy for migraine on nearly daily basis for other indications. Note: Low dose aspirin (for example; 81 mg) used for cardiovascular disease prevention is allowed.

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

Primary outcomes:
measure: DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day -1), up to Week 12
Secondary outcomes:
measure: DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day-1), up to Week 12
measure: DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day -1), up to Week 12
measure: DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day -1), up to Week 4
measure: DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day-1), up to Week 4
measure: DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day -1), up to Week 12
measure: DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab
timeFrame: Baseline (Day -28 to Day -1), up to Week 4
measure: DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs
timeFrame: Baseline (Day 0) up to Week 12
measure: OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs
timeFrame: Week 12 up to Week 24
measure: DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
timeFrame: Baseline up to Week 12
measure: OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
timeFrame: Week 12 up to Week 24
measure: DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results
timeFrame: Baseline up to Week 12
measure: OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results
timeFrame: Week 12 up to Week 24
measure: DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results
timeFrame: Baseline up to Week 12
measure: OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results
timeFrame: Week 12 up to Week 24
measure: DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results
timeFrame: Baseline up to Week 12
measure: OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results
timeFrame: Week 12 up to Week 24
measure: DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Baseline up to Week 12
measure: OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Week 12 up to Week 24
measure: DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters
timeFrame: Baseline, Week 12
measure: OL Period: Number of Participants With Shift From Baseline to Week 24 in ECG Parameters
timeFrame: Baseline, Week 24
measure: DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events
timeFrame: Baseline up to Week 12
measure: OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events
timeFrame: Week 12 up to Week 24
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Teva Investigational Site 14742
state: Alabama
city: Long Beach
country: United States
facility: Teva Investigational Site 14729
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 14739
state: California
city: Santa Monica
country: United States
facility: Teva Investigational Site 14843
state: California
city: Colorado Springs
country: United States
facility: Teva Investigational Site 14749
state: Colorado
city: Maitland
country: United States
facility: Teva Investigational Site 14758
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 14738
state: Florida
city: Decatur
country: United States
facility: Teva Investigational Site 14760
state: Georgia
city: Meridian
country: United States
facility: Teva Investigational Site 14737
state: Idaho
city: Chicago
country: United States
facility: Teva Investigational Site 14730
state: Illinois
city: Evanston
country: United States
facility: Teva Investigational Site 14740
state: Illinois
city: Louisville
country: United States
facility: Teva Investigational Site 14735
state: Kentucky
city: Pikesville
country: United States
facility: Teva Investigational Site 14747
state: Maryland
city: Fall River
country: United States
facility: Teva Investigational Site 14750
state: Massachusetts
city: Watertown
country: United States
facility: Teva Investigational Site 14734
state: Massachusetts
city: Ann Arbor
country: United States
facility: Teva Investigational Site 14731
state: Michigan
city: Plymouth
country: United States
facility: Teva Investigational Site 14748
state: Minnesota
city: Omaha
country: United States
facility: Teva Investigational Site 14746
state: Nebraska
city: Berlin
country: United States
facility: Teva Investigational Site 14754
state: New Jersey
city: Albuquerque
country: United States
facility: Teva Investigational Site 14752
state: New Mexico
city: Amherst
country: United States
facility: Teva Investigational Site 14753
state: New York
city: Greensboro
country: United States
facility: Teva Investigational Site 14736
state: North Carolina
city: Greensboro
country: United States
facility: Teva Investigational Site 14741
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 14732
state: North Carolina
city: Lincoln
country: United States
facility: Teva Investigational Site 14761
state: Rhode Island
city: Warwick
country: United States
facility: Teva Investigational Site 14756
state: Rhode Island
city: Memphis
country: United States
facility: Teva Investigational Site 14745
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 14743
state: Tennessee
city: Austin
country: United States
facility: Teva Investigational Site 14733
state: Texas
city: West Jordan
country: United States
facility: Teva Investigational Site 14751
state: Utah
city: Brugge
country: Belgium
facility: Teva Investigational Site 37092
city: Brussels
country: Belgium
facility: Teva Investigational Site 37089
city: Hasselt
country: Belgium
facility: Teva Investigational Site 37091
city: Liege
country: Belgium
facility: Teva Investigational Site 37090
city: Brno
country: Czechia
facility: Teva Investigational Site 54162
city: Ostrava-Moravska
country: Czechia
facility: Teva Investigational Site 54165
city: Ostrava
country: Czechia
facility: Teva Investigational Site 54159
city: Pardubice
country: Czechia
facility: Teva Investigational Site 54158
city: Prague 4
country: Czechia
facility: Teva Investigational Site 54164
city: Prague
country: Czechia
facility: Teva Investigational Site 54163
city: Praha 10
country: Czechia
facility: Teva Investigational Site 54160
city: Praha 3
country: Czechia
facility: Teva Investigational Site 54161
city: Praha 8
country: Czechia
facility: Teva Investigational Site 54166
city: Rychnov nad Kneznou
country: Czechia
facility: Teva Investigational Site 54157
city: Aalborg
country: Denmark
facility: Teva Investigational Site 39051
city: Arhus
country: Denmark
facility: Teva Investigational Site 39049
city: Ballerup
country: Denmark
facility: Teva Investigational Site 39052
city: Glostrup
country: Denmark
facility: Teva Investigational Site 39048
city: Vejle
country: Denmark
facility: Teva Investigational Site 39050
city: Helsinki
country: Finland
facility: Teva Investigational Site 40034
city: Helsinki
country: Finland
facility: Teva Investigational Site 40035
city: Oulu
country: Finland
facility: Teva Investigational Site 40036
city: Tampere
country: Finland
facility: Teva Investigational Site 40033
city: Turku
country: Finland
facility: Teva Investigational Site 40032
city: Turku
country: Finland
facility: Teva Investigational Site 40037
city: Bron Cedex
country: France
facility: Teva Investigational Site 35237
city: Lille
country: France
facility: Teva Investigational Site 35238
city: Marseille
country: France
facility: Teva Investigational Site 35235
city: Nice
country: France
facility: Teva Investigational Site 35240
city: Strasbourg
country: France
facility: Teva Investigational Site 35239
city: Voiron
country: France
facility: Teva Investigational Site 35236
city: Berlin
country: Germany
facility: Teva Investigational Site 32697
city: Berlin
country: Germany
facility: Teva Investigational Site 32690
city: Bochum
country: Germany
facility: Teva Investigational Site 32694
city: Essen
country: Germany
facility: Teva Investigational Site 32699
city: Goppingen
country: Germany
facility: Teva Investigational Site 32692
city: Halle
country: Germany
facility: Teva Investigational Site 32691
city: Hamburg
country: Germany
facility: Teva Investigational Site 32698
city: Kiel
country: Germany
facility: Teva Investigational Site 32700
city: Konigstein im Taunus
country: Germany
facility: Teva Investigational Site 32695
city: Muenchen
country: Germany
facility: Teva Investigational Site 32689
city: Rostock
country: Germany
facility: Teva Investigational Site 32701
city: Ulm
country: Germany
facility: Teva Investigational Site 32693
city: Firenze
country: Italy
facility: Teva Investigational Site 30199
city: Roma
country: Italy
facility: Teva Investigational Site 30204
city: Amsterdam
country: Netherlands
facility: Teva Investigational Site 38126
city: Blaricum
country: Netherlands
facility: Teva Investigational Site 38127
city: Leiden
country: Netherlands
facility: Teva Investigational Site 38124
city: Tilburg
country: Netherlands
facility: Teva Investigational Site 38125
city: Krakow
country: Poland
facility: Teva Investigational Site 53420
city: Krakow
country: Poland
facility: Teva Investigational Site 53425
city: Lodz
country: Poland
facility: Teva Investigational Site 53422
city: Lodz
country: Poland
facility: Teva Investigational Site 53424
city: Lublin
country: Poland
facility: Teva Investigational Site 53418
city: Poznan
country: Poland
facility: Teva Investigational Site 53416
city: Szczecin
country: Poland
facility: Teva Investigational Site 53419
city: Warszawa
country: Poland
facility: Teva Investigational Site 53417
city: Warszawa
country: Poland
facility: Teva Investigational Site 53423
city: Barcelona
country: Spain
facility: Teva Investigational Site 31231
city: Madrid
country: Spain
facility: Teva Investigational Site 31235
city: Madrid
country: Spain
facility: Teva Investigational Site 31236
city: Pamplona
country: Spain
facility: Teva Investigational Site 31226
city: Santander
country: Spain
facility: Teva Investigational Site 31229
city: Santiago de Compostela
country: Spain
facility: Teva Investigational Site 31230
city: Sevilla
country: Spain
facility: Teva Investigational Site 31234
city: Valencia
country: Spain
facility: Teva Investigational Site 31233
city: Valencia
country: Spain
facility: Teva Investigational Site 31227
city: Valladolid
country: Spain
facility: Teva Investigational Site 31225
city: Zaragoza
country: Spain
facility: Teva Investigational Site 31228
city: Helsingborg
country: Sweden
facility: Teva Investigational Site 42050
city: Huddinge
country: Sweden
facility: Teva Investigational Site 42049
city: Lund
country: Sweden
facility: Teva Investigational Site 42051
city: Stockholm
country: Sweden
facility: Teva Investigational Site 42052
city: Stockholm
country: Sweden
facility: Teva Investigational Site 42054
city: Bad Zurzach
country: Switzerland
facility: Teva Investigational Site 45018
city: Bern
country: Switzerland
facility: Teva Investigational Site 45016
city: Lugano
country: Switzerland
facility: Teva Investigational Site 45017
city: Glasgow
country: United Kingdom
facility: Teva Investigational Site 34231
city: Hull
country: United Kingdom
facility: Teva Investigational Site 34232
city: London
country: United Kingdom
facility: Teva Investigational Site 34233
city: Oxford
country: United Kingdom
facility: Teva Investigational Site 34230
city: Salford
country: United Kingdom
facility: Teva Investigational Site 34235
city: Stoke-on-Trent
country: United Kingdom
facility: Teva Investigational Site 34236
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References:
citation: McAllister P, Cohen JM, Campos VR, Ning X, Janka L, Barash S. Impact of fremanezumab on disability outcomes in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. J Headache Pain. 2022 Aug 29;23(1):112. doi: 10.1186/s10194-022-01438-4.
citation: Diener HC, McAllister P, Jurgens TP, Kessler Y, Ning X, Cohen JM, Campos VR, Barash S, Silberstein SD. Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. Cephalalgia. 2022 Jul;42(8):769-780. doi: 10.1177/03331024221076485. Epub 2022 Mar 25.
citation: Lampl C, Rapoport AM, Cohen JM, Barash S, Ramirez Campos V, Seminerio MJ, Ning X, Silberstein SD. Efficacy and quality-of-life improvements with fremanezumab treatment in patients with difficult-to-treat migraine with associated neurological dysfunction. Eur J Neurol. 2022 Jul;29(7):2129-2137. doi: 10.1111/ene.15328. Epub 2022 Mar 29.
citation: MaassenVanDenBrink A, Terwindt GM, Cohen JM, Barash S, Campos VR, Galic M, Ning X, Karppa M. Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study. J Headache Pain. 2021 Dec 18;22(1):152. doi: 10.1186/s10194-021-01336-1.
citation: Nahas SJ, Naegel S, Cohen JM, Ning X, Janka L, Campos VR, Krasenbaum LJ, Holle-Lee D, Kudrow D, Lampl C. Efficacy and safety of fremanezumab in clinical trial participants aged >/=60 years with episodic or chronic migraine: pooled results from 3 randomized, double-blind, placebo-controlled phase 3 studies. J Headache Pain. 2021 Nov 24;22(1):141. doi: 10.1186/s10194-021-01351-2.
citation: Ashina M, Cohen JM, Galic M, Campos VR, Barash S, Ning X, Kessler Y, Janka L, Diener HC. Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study. J Headache Pain. 2021 Jul 10;22(1):68. doi: 10.1186/s10194-021-01279-7.
citation: Pazdera L, Cohen JM, Ning X, Campos VR, Yang R, Pozo-Rosich P. Fremanezumab for the Preventive Treatment of Migraine: Subgroup Analysis by Number of Prior Preventive Treatments with Inadequate Response. Cephalalgia. 2021 Sep;41(10):1075-1088. doi: 10.1177/03331024211008401. Epub 2021 May 14.
citation: Spierings ELH, Karppa M, Ning X, Cohen JM, Campos VR, Yang R, Reuter U. Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial. J Headache Pain. 2021 Apr 16;22(1):26. doi: 10.1186/s10194-021-01232-8.
citation: Ferrari MD, Diener HC, Ning X, Galic M, Cohen JM, Yang R, Mueller M, Ahn AH, Schwartz YC, Grozinski-Wolff M, Janka L, Ashina M. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019 Sep 21;394(10203):1030-1040. doi: 10.1016/S0140-6736(19)31946-4. Epub 2019 Aug 16.