Clinical trial NCT04041284: A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Extension to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Migraine
Major Depressive Disorder
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-01
Enrollment: 353
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: PREVENTION

Brief summary: The primary objective is to evaluate the efficacy of monthly 225 mg sc fremanezumab in adult participants with migraine and major depressive disorder (MDD)

The secondary objectives are to evaluate the efficacy of monthly 225 mg sc of fremanezumab in adult participants with migraine and MDD on the reduction of MDD symptoms, responder rates in monthly migraine days, improving quality of life, improving disability, and the safety and tolerability of monthly 225 mg sc and quarterly 675 mg sc fremanezumab in adult participants with migraine and MDD.

The total duration of participant participation in the study is planned to be approximately 28 weeks.


Eligibility criteria: Inclusion Criteria:

* The participant has a diagnosis of migraine with onset at ≤50 years of age.
* Prior to the screening visit 1 the participant has a 12-month history of either migraine or headache consistent with migraine
* The participant agrees not to initiate any migraine preventive during the study. Up to 30% of participants, however, may take a single such medication previously prescribed for the treatment of migraine.
* The participant has a history of major depressive disorder (MDD) at least 12 months prior to the screening visit. Participants may take a single medication prescribed for the treatment of depression as long as the dose of that medication has been stable for at least 8 weeks prior to the screening visit and expects to remain at the stable dose throughout the study.
* The participant has a body weight ≥ 45 kg and a body mass index within the range of 17.5 to 34.9 kg/m2, inclusive.
* Women of child-bearing potential whose male partners are potentially fertile (ie, no vasectomy) must use highly effective birth control methods for the duration of the study and for 6 months after discontinuation of IMP.
* Men must be sterile or, if they are potentially fertile/reproductively competent (not congenitally sterile) and their female partners are of child-bearing potential, must use a condom for the duration of the study and for 6 months after discontinuation of IMP.

NOTE: Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

* The participant has failed 4 or more different medication classes to treat depression in their lifetime.
* The participant has used an intervention/device (eg, scheduled nerve blocks, implantable vagal nerve stimulation, and transcranial magnetic stimulation) for migraine or depression during the 2 months prior to screening.
* The participant has used electroconvulsive therapy at any time.
* The participant suffers from constant or nearly constant headache, defined as having headaches for more than 80% of the time he/she is awake, and less than 4 days without headache per month. Daily headache is acceptable if participant has headaches 80% or less of the time he/she is awake on most days.
* The participant has a clinical history of a severe or uncontrolled psychiatric disorder, to include the following, or at the discretion of the investigator for any clinically significant psychiatric history that would likely interfere with full participation in the study:

  * Lifetime exclusion: suicide attempt
  * In the past 6 months exclusion: suicidal ideation, or other psychoactive spectrum disorders including schizoaffective disorder, delusional disorder, depression with psychotic features, and catatonic disorder.
* The participant has a known infection or history of human immunodeficiency virus, tuberculosis, any history of Lyme disease, or chronic hepatitis B or C infection.
* The participant has a past or current history of cancer, except for appropriately treated non-melanoma skin carcinoma.
* The participant is a pregnant or nursing female or plans to become pregnant during the study, including the 6-month period after the administration of the last dose.
* The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies, or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome.
* 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 a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
* The participant has participated in a clinical study of a new chemical entity or a prescription medicine within 2 months of the screening visit or 3 months in case of biologics if the half-life of the biologics is unknown or 5 half-lives, whichever is longer, or is currently participating in another study of an IMP (or a medical device).
* The participant has failed treatment (based on tolerability and/or a lack of efficacy) with any monoclonal antibodies targeting the CGRP pathway (erenumab, eptinezumab, galcanezumab, or fremanezumab) or have taken the medications within 5 half-lives of the screening visit (V1) or take them during the study.
* The participant has any clinically significant uncontrolled medical condition (treated or untreated).
* The participant has a history of alcohol or drug abuse in the opinion of the investigator.
* The participant has evidence or medical history of psychotic symptoms as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria such as delusions, hallucinations, or disorganized speech in the past 1 month.

NOTE: Additional criteria apply, please contact the investigator for more information

Primary outcomes:
measure: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week DB Treatment Phase After the First Dose of Study Drug
timeFrame: Baseline (Day -28 to Day -1), up to Week 12
Secondary outcomes:
measure: Change From Baseline in Hamilton Depression Rating Scale-17 (HAM-D 17) Items Total Score at Week 8
timeFrame: Baseline, Week 8
measure: Number of Participants With ≥50% Reduction in Monthly Average Number of Migraine Days During the 12 Weeks After the First Dose of Study Drug
timeFrame: Baseline (Day -28 to Day -1) up to Week 12
measure: Change From Baseline in Migraine-Specific Quality of Life (MSQoL) Questionnaire Role Function-Restrictive and Role Function-Preventive Domain Scores at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12
timeFrame: Baseline, Weeks 4, 8, and 12
measure: Change From Baseline in 6-Item Headache Impact Test (HIT-6) Disability Score at Week 12
timeFrame: Baseline, Week 12
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Week 24
measure: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Baseline up to Week 24
measure: Number of Participants With Clinically Significant Abnormal Physical Examination Findings
timeFrame: Baseline up to Week 24
measure: Number of Participants With Drug Hypersensitivity and Seasonal Allergy
timeFrame: Baseline up to Week 24
measure: Number of Participants Who Used Concomitant Medication
timeFrame: Baseline up to Week 24
measure: Number of Participants Who Used Concomitant Medication for Migraine/Headache
timeFrame: Baseline up to Week 24
measure: Number of Participants Who Did Not Complete the Study Due to AE
timeFrame: Baseline up to Week 24
measure: Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Weeks 4, 8, 12, and 24
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Teva Investigational Site 14330
state: Arkansas
city: San Diego
country: United States
facility: Teva Investigational Site 14337
state: California
city: Denver
country: United States
facility: Teva Investigational Site 14342
state: Colorado
city: Stamford
country: United States
facility: Teva Investigational Site 14332
state: Connecticut
city: Hialeah
country: United States
facility: Teva Investigational Site 14329
state: Florida
city: Jacksonville
country: United States
facility: Teva Investigational Site 14334
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 14341
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 14411
state: Florida
city: Pikesville
country: United States
facility: Teva Investigational Site 14336
state: Maryland
city: Waltham
country: United States
facility: Teva Investigational Site 14331
state: Massachusetts
city: Bolivar
country: United States
facility: Teva Investigational Site 14343
state: Missouri
city: Bronx
country: United States
facility: Teva Investigational Site 14345
state: New York
city: Brooklyn
country: United States
facility: Teva Investigational Site 14335
state: New York
city: Portland
country: United States
facility: Teva Investigational Site 14340
state: Oregon
city: Philadelphia
country: United States
facility: Teva Investigational Site 14338
state: Pennsylvania
city: Memphis
country: United States
facility: Teva Investigational Site 14333
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 14339
state: Tennessee
city: Chocen
country: Czechia
facility: Teva Investigational Site 54190
city: Praha 4
country: Czechia
facility: Teva Investigational Site 54183
city: Praha 6
country: Czechia
facility: Teva Investigational Site 54184
city: Praha 8
country: Czechia
facility: Teva Investigational Site 54185
city: Rychnov nad Kneznou
country: Czechia
facility: Teva Investigational Site 54186
city: Kuopio
country: Finland
facility: Teva Investigational Site 40058
city: Oulu
country: Finland
facility: Teva Investigational Site 40057
city: Tampere
country: Finland
facility: Teva Investigational Site 40056
city: Turku
country: Finland
facility: Teva Investigational Site 40055
city: Bron
country: France
facility: Teva Investigational Site 35265
city: Saint-Priest-en-Jarez
country: France
facility: Teva Investigational Site 35267
city: Dresden
country: Germany
facility: Teva Investigational Site 32736
city: Essen
country: Germany
facility: Teva Investigational Site 32737
city: Essen
country: Germany
facility: Teva Investigational Site 32731
city: Leipzig
country: Germany
facility: Teva Investigational Site 32734
city: Mittweida
country: Germany
facility: Teva Investigational Site 32732
city: Westerstede
country: Germany
facility: Teva Investigational Site 32733
city: Athens
country: Greece
facility: Teva Investigational Site 63075
city: Glyfada
country: Greece
facility: Teva Investigational Site 63076
city: Marousi
country: Greece
facility: Teva Investigational Site 63077
city: Hadera
country: Israel
facility: Teva Investigational Site 80172
city: Holon
country: Israel
facility: Teva Investigational Site 80173
city: Jerusalem
country: Israel
facility: Teva Investigational Site 80177
city: Petah Tikva
country: Israel
facility: Teva Investigational Site 80178
city: Rehovot
country: Israel
facility: Teva Investigational Site 80175
city: Catanzaro
country: Italy
facility: Teva Investigational Site 30242
city: Firenze
country: Italy
facility: Teva Investigational Site 30236
city: Milan
country: Italy
facility: Teva Investigational Site 30237
city: Pavia
country: Italy
facility: Teva Investigational Site 30235
city: Roma
country: Italy
facility: Teva Investigational Site 30232
city: Rome
country: Italy
facility: Teva Investigational Site 30234
city: Krakow
country: Poland
facility: Teva Investigational Site 53447
city: Poznan
country: Poland
facility: Teva Investigational Site 53445
city: Warszawa
country: Poland
facility: Teva Investigational Site 53446
city: Wroclaw
country: Poland
facility: Teva Investigational Site 53448
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50482
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50483
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50480
city: Nizhnij Novgorod
country: Russian Federation
facility: Teva Investigational Site 50481
city: Sevilla
country: Spain
facility: Teva Investigational Site 31276
city: Valencia
country: Spain
facility: Teva Investigational Site 31274
city: Valladolid
country: Spain
facility: Teva Investigational Site 31272
city: Zaragoza
country: Spain
facility: Teva Investigational Site 31273
city: Kiyv
country: Ukraine
facility: Teva Investigational Site 58319
city: Odesa
country: Ukraine
facility: Teva Investigational Site 58321
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 58320
city: London
country: United Kingdom
facility: Teva Investigational Site 34254
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: