A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder
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 |
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Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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Placebo Comparator: Placebo
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Drug: Placebo
Matching Placebo
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Outcome Measures
Primary Outcome Measures
- Mean change in the monthly average number of migraine days [Baseline - Week 12]
Secondary Outcome Measures
- 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
- Number of participants with 50% or more reduction of migraine days [Baseline - Week 12]
- 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.
- Mean change in disability score for overall impact as measured by Clinical Global Impression-Severity (CGI-S) [Day 1, Week 4, 8, 12]
- Mean change in disability score for overall impact as measured by Headache Impact Test (HIT-6) [Day 1, Week 12]
- Number of participants reporting adverse events [Up to Week 24]
Adverse events include clinically significant vital signs, physical exam findings, hypersensitivity, and allergic reactions
- Number of participants who use concomitant medication for adverse events [Up to Week 24]
- Percentage of participants who do not complete the study due to adverse events [Up to Week 24]
- 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
Inclusion Criteria:
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The participant has a diagnosis of migraine with onset at ≤50 years of age.
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Prior to the screening visit 1 the participant has a 12-month history of either migraine or headache consistent with migraine
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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.
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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.
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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.
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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.
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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:
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The participant has failed 4 or more different medication classes to treat depression in their lifetime.
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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.
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The participant has used electroconvulsive therapy at any time.
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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.
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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:
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Lifetime exclusion: suicide attempt
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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.
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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.
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The participant has a past or current history of cancer, except for appropriately treated non-melanoma skin carcinoma.
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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.
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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.
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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.
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The participant has a history of hypersensitivity reactions to injected proteins, including monoclonal antibodies.
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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).
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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.
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The participant has any clinically significant uncontrolled medical condition (treated or untreated).
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The participant has a history of alcohol or drug abuse in the opinion of the investigator.
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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 | |
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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.- TV48125-MH-40142
- 2019-001989-15