A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04041284
Collaborator
(none)
353
64
2
35.6
5.5
0.2

Study Details

Study Description

Brief Summary

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

The secondary objectives are to evaluate the efficacy of monthly 225 mg sc of fremanezumab in adult patients 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 patients with migraine and MDD.

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

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
353 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
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
Actual Study Start Date :
Sep 13, 2019
Anticipated Primary Completion Date :
Sep 1, 2022
Anticipated Study Completion Date :
Sep 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: fremanezumab

monthly 225 mg. In the open-label extension phase starting at week 12, all patients will receive active treatment with a quarterly dose of 675 mg sc

Drug: Fremanezumab
Monthly 225 mg subcutaneous
Other Names:
  • TEV-48125, LBR-101, PF-04427429, RN307
  • Placebo Comparator: Placebo

    Drug: Placebo
    Matching Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Mean change in the monthly average number of migraine days [Baseline - Week 12]

    Secondary Outcome Measures

    1. Mean change in depression symptoms [Day 1-Week 8]

      Mean change measured by Hamilton Depression Rating Scale-17 items (HAM-D 17) Higher scores indicate greater depression severity; lower scores indicate minimal/no presence of depression

    2. Number of participants with 50% or more reduction of migraine days [Baseline - Week 12]

    3. Mean change in quality of life [Randomization (day 1) - week 12]

      Measured by Migraine-Specific Quality of Life (MSQoL) questionnaire. The 14-item instrument measures how migraines affect daily functioning across three domains: Role function Restrictions, Role function prevention, and Emotional Function. Scores range from 0 to 100. Higher scores indicate better quality of life.

    4. Mean change in disability score for overall impact as measured by Clinical Global Impression-Severity (CGI-S) [Day 1, Week 4, 8, 12]

    5. Mean change in disability score for overall impact as measured by Headache Impact Test (HIT-6) [Day 1, Week 12]

    6. Number of participants reporting adverse events [Up to Week 24]

      Adverse events include clinically significant vital signs, physical exam findings, hypersensitivity, and allergic reactions

    7. Number of participants who use concomitant medication for adverse events [Up to Week 24]

    8. Percentage of participants who do not complete the study due to adverse events [Up to Week 24]

    9. Change in eC-SSRS (electronic Columbia-Suicide Severity Rating Scale) scores [Baseline, Week 24]

      Suicidal ideation is assessed at 5 distinct levels of increasing severity: Level 1: Wish to be Dead Level 2: Non-Specific Active Suicidal Thoughts Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan Level 5: Active Suicidal Ideation with Specific Plan and Intent

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Teva Investigational Site 14330 Little Rock Arkansas United States 72205
    2 Teva Investigational Site 14337 San Diego California United States 92103
    3 Teva Investigational Site 14342 Denver Colorado United States 80218
    4 Teva Investigational Site 14332 Stamford Connecticut United States 06905
    5 Teva Investigational Site 14329 Hialeah Florida United States 33012
    6 Teva Investigational Site 14334 Jacksonville Florida United States 32256
    7 Teva Investigational Site 14341 Orlando Florida United States 32801
    8 Teva Investigational Site 14411 Tampa Florida United States 33634
    9 Teva Investigational Site 14336 Pikesville Maryland United States 21208
    10 Teva Investigational Site 14331 Waltham Massachusetts United States 02451
    11 Teva Investigational Site 14343 Bolivar Missouri United States 65613
    12 Teva Investigational Site 14345 Bronx New York United States 10461
    13 Teva Investigational Site 14335 Brooklyn New York United States 11229
    14 Teva Investigational Site 14340 Portland Oregon United States 97214
    15 Teva Investigational Site 14338 Philadelphia Pennsylvania United States 19107
    16 Teva Investigational Site 14333 Memphis Tennessee United States 38119
    17 Teva Investigational Site 14339 Nashville Tennessee United States 37203
    18 Teva Investigational Site 54190 Chocen Czechia 565 01
    19 Teva Investigational Site 54184 Prague 10 Czechia 160 00
    20 Teva Investigational Site 54183 Prague 4 Czechia 140 59
    21 Teva Investigational Site 54185 Praha 8 Czechia 186 00
    22 Teva Investigational Site 54186 Rychnov nad Kneznou Czechia 516 01
    23 Teva Investigational Site 40058 Kuopio Finland 70600
    24 Teva Investigational Site 40057 Oulu Finland 90220
    25 Teva Investigational Site 40056 Tampere Finland 33100
    26 Teva Investigational Site 40055 Turku Finland 20100
    27 Teva Investigational Site 35265 Bron France 69500
    28 Teva Investigational Site 35267 Saint Priest en Jarez France 42277
    29 Teva Investigational Site 32736 Dresden Germany 1307
    30 Teva Investigational Site 32731 Essen Germany 45122
    31 Teva Investigational Site 32737 Essen Germany 45133
    32 Teva Investigational Site 32734 Leipzig Germany 4275
    33 Teva Investigational Site 32732 Mittweida Germany 09648
    34 Teva Investigational Site 32733 Westerstede Germany 26655
    35 Teva Investigational Site 63075 Athens Greece 11528
    36 Teva Investigational Site 63076 Glyfada Greece 16675
    37 Teva Investigational Site 63077 Marousi Greece 15125
    38 Teva Investigational Site 80172 Hadera Israel 3810101
    39 Teva Investigational Site 80173 Holon Israel 5822012
    40 Teva Investigational Site 80177 Jerusalem Israel 9112001
    41 Teva Investigational Site 80178 Petah Tikva Israel 4941492
    42 Teva Investigational Site 80175 Rehovot Israel 7661041
    43 Teva Investigational Site 30242 Catanzaro Italy 88100
    44 Teva Investigational Site 30236 Firenze Italy 50134
    45 Teva Investigational Site 30237 Milano Italy 20132
    46 Teva Investigational Site 30235 Pavia Italy 27100
    47 Teva Investigational Site 30232 Rome Italy 00128
    48 Teva Investigational Site 30234 Rome Italy 163
    49 Teva Investigational Site 53447 Krakow Poland 30-539
    50 Teva Investigational Site 53445 Poznan Poland 60-529
    51 Teva Investigational Site 53446 Warszawa Poland 01-737
    52 Teva Investigational Site 53448 Wroclaw Poland 52-416
    53 Teva Investigational Site 50482 Moscow Russian Federation 119021
    54 Teva Investigational Site 50483 Moscow Russian Federation 121467
    55 Teva Investigational Site 50480 Moscow Russian Federation 129128
    56 Teva Investigational Site 50481 Nizhnij Novgorod Russian Federation 603137
    57 Teva Investigational Site 31276 Sevilla Spain 41013
    58 Teva Investigational Site 31274 Valencia Spain 46026
    59 Teva Investigational Site 31272 Valladolid Spain 47003
    60 Teva Investigational Site 31273 Zaragoza Spain 50009
    61 Teva Investigational Site 58319 Kyiv Ukraine 4080
    62 Teva Investigational Site 58321 Odesa Ukraine 650000
    63 Teva Investigational Site 58320 Vinnytsya Ukraine 21018
    64 Teva Investigational Site 34254 London United Kingdom SE1 7EH

    Sponsors and Collaborators

    • Teva Branded Pharmaceutical Products R&D, Inc.

    Investigators

    • Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT04041284
    Other Study ID Numbers:
    • TV48125-MH-40142
    • 2019-001989-15
    First Posted:
    Aug 1, 2019
    Last Update Posted:
    Aug 17, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 17, 2022