Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2019-001989-15 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| fremanezumab | Experimental | monthly 225 mg. In the open-label extension phase starting at week 12, all participants will receive active treatment with a quarterly dose of 675 mg sc |
|
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fremanezumab | Drug | Monthly 225 mg subcutaneous |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week DB Treatment Phase After the First Dose of Study Drug | A migraine day was defined as when at least 1 of following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine (where only 1 migraine criterion was missing); a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)*28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA). | Baseline (Day -28 to Day -1), up to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Hamilton Depression Rating Scale-17 (HAM-D 17) Items Total Score at Week 8 | The HAM-D 17 is a list of 17 items used to determine a participant's level of depression. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 (none/absent) to 2 (severe symptom) include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 (none/absent) to 4 (severe symptom): Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The HAM-D17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAM-D17 scores indicate more severe depression. LS mean was calculated using mixed-effects model for repeated measures (MMRM). |
Not provided
Inclusion Criteria:
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:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Teva Medical Expert, MD | Teva Branded Pharmaceutical Products R&D, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Teva Investigational Site 14330 | Little Rock | Arkansas | 72205 | United States | ||
| Teva Investigational Site 14337 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40323613 | Derived | Lipton RB, Ramirez Campos V, Roth-Ben Arie Z, Galic M, Mitsikostas D, Tassorelli C, Denysenko L, Cohen JM. Fremanezumab for the Treatment of Patients With Migraine and Comorbid Major Depressive Disorder: The UNITE Randomized Clinical Trial. JAMA Neurol. 2025 Jun 1;82(6):560-569. doi: 10.1001/jamaneurol.2025.0806. |
Not provided
Not provided
Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.
Not provided
Not provided
Not provided
Not provided
Of the 540 participants screened, 353 participants were enrolled/randomized.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo matched to fremanezumab subcutaneously (SC) during the 12-week double blind (DB) period and then continued into the open-label (OL) extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| DB Phase (12 Weeks) |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 4, 2020 | Aug 23, 2023 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Matching Placebo |
|
| Baseline, Week 8 |
| Number of Participants With ≥50% Reduction in Monthly Average Number of Migraine Days During the 12 Weeks After the First Dose of Study Drug | A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling the 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)*28. | Baseline (Day -28 to Day -1) up to Week 12 |
| Change From Baseline in Migraine-Specific Quality of Life (MSQoL) Questionnaire Role Function-Restrictive and Role Function-Preventive Domain Scores at Week 12 | The MSQoL version 2.1 is a 14-item questionnaire that assesses the impact of migraine and migraine treatment on a participant's quality of life during the previous 4 weeks. Each item is scored on a 6-point scale where: 1=none of the time to 6=all of the time. The MSQoL measures the degree to which performance of normal activities is limited by migraine (Role Function-Restrictive domain comprising 7 items; score range 7 to 42), the degree to which performance of normal activities is prevented by migraine (Role Function-Preventive domain comprising 4 items; score range 4 to 24), and the emotional effects of migraine (Emotional Function domain comprising 3 items; score range 3 to 18). Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health-related quality of life. LS mean was calculated using MMRM. | Baseline, Week 12 |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12 | The CGI-S is a short questionnaire filled out by the investigator that rates a participant's mental health from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). | Baseline, Weeks 4, 8, and 12 |
| Change From Baseline in 6-Item Headache Impact Test (HIT-6) Disability Score at Week 12 | Migraine related disability was assessed using the HIT-6. The questionnaire measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It also assesses headache severity. Each question was answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always). The total score was obtained from summation of the 6 question points. The HIT-6 total score ranges between 36 and 78, with higher scores reflecting greater impact. | Baseline, Week 12 |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Baseline up to Week 24 |
| Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Criteria for potentially clinically significant vital signs values: Pulse: ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm or ≤50 bpm and decrease from baseline of ≥15 bpm; Systolic blood pressure (SBP): ≥180 millimeters of mercury (mmHg) and increase from baseline of ≥20 mmHg or ≤90 mmHg and decrease from baseline of ≥20 mmHg; Diastolic blood pressure (DBP): ≥105 mmHg and increase from baseline of ≥15 mmHg or ≤50 mmHg and decrease from baseline of ≥15 mmHg; Respiratory rate: <10 breaths per minute; and Body temperature: ≥38.3 degrees celsius (ºC) and change from baseline of ≥1.1ºC. | Baseline up to Week 24 |
| Number of Participants With Clinically Significant Abnormal Physical Examination Findings | Physical examination included height, weight, general appearance; head, eyes, ears, nose, and throat; chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. Clinical significance was per investigator's discretion. | Baseline up to Week 24 |
| Number of Participants With Drug Hypersensitivity and Seasonal Allergy | Baseline up to Week 24 |
| Number of Participants Who Used Concomitant Medication | Concomitant medications included agents acting on the renin-angiotensin system, analgesics, antibacterials for systemic use, antihistamines for systemic use, anti-inflammatory and antirheumatic products, beta-blocking agents, drugs for acid related disorder, lipid modifying agents, mineral supplement, other gynecologicals, psychoanaleptics, psycholeptics, sex hormones and modulators of the genital system, thyroid therapy, vaccines, and vitamins. | Baseline up to Week 24 |
| Number of Participants Who Used Concomitant Medication for Migraine/Headache | Concomitant medications for migraine/headache included analgesics, antiepileptics, muscle relaxants, anti-inflammatory and antirheumatic products, agents acting on the renin-angiotensin system, anesthetics, antianemic preparations, antibacterials for systemic use, antihistamines for systemic use, beta-blocking agents, lipid modifying agents, mineral supplement, other gynecologicals, psychoanaleptics, psycholeptics, sex hormones and modulators of the genital system, thyroid therapy, vaccines, vitamins etc. | Baseline up to Week 24 |
| Number of Participants Who Did Not Complete the Study Due to AE | Baseline up to Week 24 |
| Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in 10 categories: 1=Wish to be dead; 2=Non-specific active suicidal thoughts; 3=Active suicidal ideation with any methods (not plan) without intent to act; 4=Active suicidal ideation with some intent to act, without specific plan; 5=Active suicidal ideation with specific plan and intent; 6=Preparatory acts or behavior; 7=Aborted attempt; 8=Interrupted attempt; 9=Non-fatal suicide attempt; and 10=Completed suicide. Participants who responded "Yes" to any category were considered Positive, participants who responded "No" for all categories were considered Negative, and participants who were evaluable but did not complete the questionnaire were considered Incomplete. A Positive response was considered as a worse outcome and the investigator determined if further evaluation was needed. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module. | Baseline, Weeks 4, 8, 12, and 24 |
| San Diego |
| California |
| 92103 |
| United States |
| Teva Investigational Site 14342 | Denver | Colorado | 80218 | United States |
| Teva Investigational Site 14332 | Stamford | Connecticut | 06905 | United States |
| Teva Investigational Site 14329 | Hialeah | Florida | 33012 | United States |
| Teva Investigational Site 14334 | Jacksonville | Florida | 32256 | United States |
| Teva Investigational Site 14341 | Orlando | Florida | 32801 | United States |
| Teva Investigational Site 14411 | Tampa | Florida | 33634 | United States |
| Teva Investigational Site 14336 | Pikesville | Maryland | 21208 | United States |
| Teva Investigational Site 14331 | Waltham | Massachusetts | 02451 | United States |
| Teva Investigational Site 14343 | Bolivar | Missouri | 65613 | United States |
| Teva Investigational Site 14335 | Brooklyn | New York | 11229 | United States |
| Teva Investigational Site 14345 | The Bronx | New York | 10461 | United States |
| Teva Investigational Site 14340 | Portland | Oregon | 97214 | United States |
| Teva Investigational Site 14338 | Philadelphia | Pennsylvania | 19107 | United States |
| Teva Investigational Site 14333 | Memphis | Tennessee | 38119 | United States |
| Teva Investigational Site 14339 | Nashville | Tennessee | 37203 | United States |
| Teva Investigational Site 54190 | Choceň | 565 01 | Czechia |
| Teva Investigational Site 54183 | Prague | 140 59 | Czechia |
| Teva Investigational Site 54184 | Prague | 160 00 | Czechia |
| Teva Investigational Site 54185 | Prague | 186 00 | Czechia |
| Teva Investigational Site 54186 | Rychnov nad Kněžnou | 516 01 | Czechia |
| Teva Investigational Site 40058 | Kuopio | 70600 | Finland |
| Teva Investigational Site 40057 | Oulu | 90220 | Finland |
| Teva Investigational Site 40056 | Tampere | 33100 | Finland |
| Teva Investigational Site 40055 | Turku | 20100 | Finland |
| Teva Investigational Site 35265 | Bron | 69500 | France |
| Teva Investigational Site 35267 | Saint-Priest-en-Jarez | 42277 | France |
| Teva Investigational Site 32736 | Dresden | 01307 | Germany |
| Teva Investigational Site 32737 | Essen | 45133 | Germany |
| Teva Investigational Site 32731 | Essen | 45147 | Germany |
| Teva Investigational Site 32734 | Leipzig | 04275 | Germany |
| Teva Investigational Site 32732 | Mittweida | 09648 | Germany |
| Teva Investigational Site 32733 | Westerstede | 26655 | Germany |
| Teva Investigational Site 63075 | Athens | 11528 | Greece |
| Teva Investigational Site 63076 | Glyfada | 166 75 | Greece |
| Teva Investigational Site 63077 | Marousi | 15125 | Greece |
| Teva Investigational Site 80172 | Hadera | 3810101 | Israel |
| Teva Investigational Site 80173 | Holon | 5822012 | Israel |
| Teva Investigational Site 80177 | Jerusalem | 9112001 | Israel |
| Teva Investigational Site 80178 | Petah Tikva | 4941492 | Israel |
| Teva Investigational Site 80175 | Rehovot | 7661041 | Israel |
| Teva Investigational Site 30242 | Catanzaro | 88100 | Italy |
| Teva Investigational Site 30236 | Florence | 50134 | Italy |
| Teva Investigational Site 30237 | Milan | 20132 | Italy |
| Teva Investigational Site 30235 | Pavia | 27100 | Italy |
| Teva Investigational Site 30232 | Roma | 00128 | Italy |
| Teva Investigational Site 30234 | Rome | 00163 | Italy |
| Teva Investigational Site 53447 | Krakow | 30-539 | Poland |
| Teva Investigational Site 53445 | Poznan | 60-529 | Poland |
| Teva Investigational Site 53446 | Warsaw | 01-737 | Poland |
| Teva Investigational Site 53448 | Wroclaw | 52-416 | Poland |
| Teva Investigational Site 50482 | Moscow | 119021 | Russia |
| Teva Investigational Site 50483 | Moscow | 121467 | Russia |
| Teva Investigational Site 50480 | Moscow | 129128 | Russia |
| Teva Investigational Site 50481 | Nizhny Novgorod | 603137 | Russia |
| Teva Investigational Site 31276 | Seville | 41013 | Spain |
| Teva Investigational Site 31274 | Valencia | 46026 | Spain |
| Teva Investigational Site 31272 | Valladolid | 47003 | Spain |
| Teva Investigational Site 31273 | Zaragoza | 50009 | Spain |
| Teva Investigational Site 58319 | Kiyv | 04080 | Ukraine |
| Teva Investigational Site 58321 | Odesa | 650000 | Ukraine |
| Teva Investigational Site 58320 | Vinnytsia | 21018 | Ukraine |
| Teva Investigational Site 34254 | London | SE1 7EH | United Kingdom |
| Fremanezumab |
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| DB Safety Analysis Set | All randomized participants who received at least 1 dose of study drug during the DB treatment period. |
|
| DB Modified Intent-to-treat (mITT) Analysis Set | All randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| OL Phase (12 Weeks) |
|
|
The intent-to-treat (ITT) analysis set included all randomized participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo matched to fremanezumab SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| BG001 | Fremanezumab | Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Number of migraine days | A migraine day was defined as when at least 1 of following occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine (where only 1 migraine criterion was missing); demonstrating a headache of any duration that was treated with migraine-specific medications; and a calendar day that was immediately consecutive of any day fulfilling the 3 criteria above, where participants report headache of any duration. | Mean | Standard Deviation | days |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week DB Treatment Phase After the First Dose of Study Drug | A migraine day was defined as when at least 1 of following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine (where only 1 migraine criterion was missing); a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)*28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA). | DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. | Posted | Least Squares Mean | Standard Error | days | Baseline (Day -28 to Day -1), up to Week 12 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Hamilton Depression Rating Scale-17 (HAM-D 17) Items Total Score at Week 8 | The HAM-D 17 is a list of 17 items used to determine a participant's level of depression. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 (none/absent) to 2 (severe symptom) include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 (none/absent) to 4 (severe symptom): Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The HAM-D17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAM-D17 scores indicate more severe depression. LS mean was calculated using mixed-effects model for repeated measures (MMRM). | DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 8 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With ≥50% Reduction in Monthly Average Number of Migraine Days During the 12 Weeks After the First Dose of Study Drug | A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling the 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)*28. | DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. | Posted | Count of Participants | Participants | Baseline (Day -28 to Day -1) up to Week 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Migraine-Specific Quality of Life (MSQoL) Questionnaire Role Function-Restrictive and Role Function-Preventive Domain Scores at Week 12 | The MSQoL version 2.1 is a 14-item questionnaire that assesses the impact of migraine and migraine treatment on a participant's quality of life during the previous 4 weeks. Each item is scored on a 6-point scale where: 1=none of the time to 6=all of the time. The MSQoL measures the degree to which performance of normal activities is limited by migraine (Role Function-Restrictive domain comprising 7 items; score range 7 to 42), the degree to which performance of normal activities is prevented by migraine (Role Function-Preventive domain comprising 4 items; score range 4 to 24), and the emotional effects of migraine (Emotional Function domain comprising 3 items; score range 3 to 18). Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health-related quality of life. LS mean was calculated using MMRM. | DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12 | The CGI-S is a short questionnaire filled out by the investigator that rates a participant's mental health from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). | DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Weeks 4, 8, and 12 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in 6-Item Headache Impact Test (HIT-6) Disability Score at Week 12 | Migraine related disability was assessed using the HIT-6. The questionnaire measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It also assesses headache severity. Each question was answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always). The total score was obtained from summation of the 6 question points. The HIT-6 total score ranges between 36 and 78, with higher scores reflecting greater impact. | DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Criteria for potentially clinically significant vital signs values: Pulse: ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm or ≤50 bpm and decrease from baseline of ≥15 bpm; Systolic blood pressure (SBP): ≥180 millimeters of mercury (mmHg) and increase from baseline of ≥20 mmHg or ≤90 mmHg and decrease from baseline of ≥20 mmHg; Diastolic blood pressure (DBP): ≥105 mmHg and increase from baseline of ≥15 mmHg or ≤50 mmHg and decrease from baseline of ≥15 mmHg; Respiratory rate: <10 breaths per minute; and Body temperature: ≥38.3 degrees celsius (ºC) and change from baseline of ≥1.1ºC. | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Clinically Significant Abnormal Physical Examination Findings | Physical examination included height, weight, general appearance; head, eyes, ears, nose, and throat; chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. Clinical significance was per investigator's discretion. | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Drug Hypersensitivity and Seasonal Allergy | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Used Concomitant Medication | Concomitant medications included agents acting on the renin-angiotensin system, analgesics, antibacterials for systemic use, antihistamines for systemic use, anti-inflammatory and antirheumatic products, beta-blocking agents, drugs for acid related disorder, lipid modifying agents, mineral supplement, other gynecologicals, psychoanaleptics, psycholeptics, sex hormones and modulators of the genital system, thyroid therapy, vaccines, and vitamins. | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Used Concomitant Medication for Migraine/Headache | Concomitant medications for migraine/headache included analgesics, antiepileptics, muscle relaxants, anti-inflammatory and antirheumatic products, agents acting on the renin-angiotensin system, anesthetics, antianemic preparations, antibacterials for systemic use, antihistamines for systemic use, beta-blocking agents, lipid modifying agents, mineral supplement, other gynecologicals, psychoanaleptics, psycholeptics, sex hormones and modulators of the genital system, thyroid therapy, vaccines, vitamins etc. | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Did Not Complete the Study Due to AE | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. | Posted | Count of Participants | Participants | Baseline up to Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in 10 categories: 1=Wish to be dead; 2=Non-specific active suicidal thoughts; 3=Active suicidal ideation with any methods (not plan) without intent to act; 4=Active suicidal ideation with some intent to act, without specific plan; 5=Active suicidal ideation with specific plan and intent; 6=Preparatory acts or behavior; 7=Aborted attempt; 8=Interrupted attempt; 9=Non-fatal suicide attempt; and 10=Completed suicide. Participants who responded "Yes" to any category were considered Positive, participants who responded "No" for all categories were considered Negative, and participants who were evaluable but did not complete the questionnaire were considered Incomplete. A Positive response was considered as a worse outcome and the investigator determined if further evaluation was needed. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module. | DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint of the respective phase of the study. | Posted | Count of Participants | Participants | Baseline, Weeks 4, 8, 12, and 24 |
|
Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Double-blind Phase: Placebo | Participants received placebo matched to fremanezumab SC during the 12-week DB period. | 0 | 177 | 1 | 177 | 0 | 177 |
| EG001 | Double-blind Phase: Fremanezumab | Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period. | 0 | 176 | 2 | 176 | 0 | 176 |
| EG002 | Open-label Phase: Placebo/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. | 0 | 165 | 3 | 165 | 0 | 165 |
| EG003 | Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. | 0 | 165 | 1 | 165 | 0 | 165 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hiatus hernia | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 24.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
|
Not provided
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research | Teva Branded Pharmaceutical Products, R&D Inc. | 888-483-8279 | USMedInfo@tevapharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 15, 2022 | Aug 23, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000604315 | fremanezumab |
Not provided
Not provided
Not provided
| Pregnancy |
|
| Other than specified |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period. |
|
|
|
| Double-blind Phase: Fremanezumab |
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period. |
|
|
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
| OG002 | Open-label Phase: Placebo/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| OG003 | Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
|
|
| OG002 | Open-label Phase: Placebo/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| OG003 | Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
|
|
| Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 |
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
|
|
|
|
| OG003 | Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
|
|
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| OG003 | Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
|
|
|
|
| OG001 | Double-blind Phase: Fremanezumab | Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period. |
| OG002 | Open-label Phase: Placebo/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
| OG003 | Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2 | Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85. |
|
|
| Positive |
|
| Title | Measurements |
|---|---|
| Incomplete |
|
| Negative |
|
| Positive |
|
| Title | Measurements |
|---|---|
| Incomplete |
|
| Negative |
|
| Positive |
|
| Title | Measurements |
|---|---|
| Incomplete |
|
| Negative |
|
| Positive |
|
| Title | Measurements |
|---|---|
| Incomplete |
|
| Negative |
|
| Positive |
|