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The purpose of the study is to determine whether monthly subcutaneous administration of LBR-101 (fremanezumab) is safe and provides migraine prevention in patients with chronic migraine.
Two distinct doses of subcutaneous LBR-101 (fremanezumab) administered monthly will be compared to placebo for safety and efficacy. The mean change from baseline in the number of cumulative headache hours measured at the 28-day period ending with week 12.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LBR-101 High Dose | Experimental | Subcutaneous High Dose LBR-101 Administered Monthly x 3 |
|
| LBR-101 Low Dose | Experimental | Subcutaneous Low Dose LBR-101 Administered Monthly x 3 |
|
| Placebo | Placebo Comparator | Subcutaneous Placebo Administered Monthly x 3 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LBR-101 High Dose | Drug | Subcutaneously Administered LBR-101 Monthly x 3 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in the Number of Monthly Cumulative Headache Hours of Any Severity on Headache Days Relative to the 28-day Post-treatment Period Ending With Week 12 | A headache 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 of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of hours with headache of any severity during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe. | Baseline to week 12 |
| Number of Participants With at Least One Adverse Event | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, 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 the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Baseline to week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in the Number of Headache Days of at Least Moderate Severity Relative to the 28-day Post-treatment Period Ending With Week 12 | A headache 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 of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of headache days of at least moderate severity during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe. |
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Inclusion Criteria:
Exclusion Criteria:
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| 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 145 | Gilbert | Arizona | 85234 | United States | ||
| Teva Investigational Site 130 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30120138 | Derived | VanderPluym J, Dodick DW, Lipton RB, Ma Y, Loupe PS, Bigal ME. Fremanezumab for preventive treatment of migraine: Functional status on headache-free days. Neurology. 2018 Sep 18;91(12):e1152-e1165. doi: 10.1212/01.wnl.0000544321.19316.40. Epub 2018 Aug 17. | |
| 29722276 | Derived | Halker Singh RB, Aycardi E, Bigal ME, Loupe PS, McDonald M, Dodick DW. Sustained reductions in migraine days, moderate-to-severe headache days and days with acute medication use for HFEM and CM patients taking fremanezumab: Post-hoc analyses from phase 2 trials. Cephalalgia. 2019 Jan;39(1):52-60. doi: 10.1177/0333102418772585. Epub 2018 May 3. |
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Participants were assigned to receive either monthly subcutaneous administration of 900 mg of LBR-101 (fremanezumab), subcutaneous loading dose of 675 mg of LBR-101 (fremanezumab) followed by monthly subcutaneous doses of 225 mg of LBR-101 (fremanezumab), or monthly subcutaneous doses of placebo.
A total of 264 participants with chronic migraine were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received subcutaneous placebo injections at one visit per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). |
| FG001 | LBR-101 Low Dose |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| LBR-101 Low Dose | Drug | Subcutaneously Administered LBR-101 Monthly x 3 |
|
|
| Placebo | Drug | Subcutaneously Administered Placebo (Vehicle) Monthly x 3 |
|
| Baseline to week 12 |
| Phoenix |
| Arizona |
| 85032 |
| United States |
| Teva Investigational Site 117 | Scottsdale | Arizona | 85259 | United States |
| Teva Investigational Site 161 | Anaheim | California | 92801 | United States |
| Teva Investigational Site 116 | Fullerton | California | 92835 | United States |
| Teva Investigational Site 119 | Long Beach | California | 90806 | United States |
| Teva Investigational Site 146 | Oceanside | California | 92056 | United States |
| Teva Investigational Site 113 | San Francisco | California | 94109 | United States |
| Teva Investigational Site 108 | Stanford | California | 94305 | United States |
| Teva Investigational Site 112 | Walnut Creek | California | 94598 | United States |
| Teva Investigational Site 132 | Boulder | Colorado | 80304 | United States |
| Teva Investigational Site 162 | Stamford | Connecticut | 06905 | United States |
| Teva Investigational Site 143 | DeLand | Florida | 32720 | United States |
| Teva Investigational Site 137 | Hialeah | Florida | 33012 | United States |
| Teva Investigational Site 101 | Jacksonville | Florida | 32216 | United States |
| Teva Investigational Site 166 | Jacksonville | Florida | 32256 | United States |
| Teva Investigational Site 129 | Maitland | Florida | 32751 | United States |
| Teva Investigational Site 167 | Orlando | Florida | 32801 | United States |
| Teva Investigational Site 139 | Ormond Beach | Florida | 32174 | United States |
| Teva Investigational Site 140 | Port Orange | Florida | 32127 | United States |
| Teva Investigational Site 149 | Atlanta | Georgia | 30342 | United States |
| Teva Investigational Site 164 | Decatur | Georgia | 30030 | United States |
| Teva Investigational Site 134 | Douglasville | Georgia | 30134 | United States |
| Teva Investigational Site 125 | Evansville | Indiana | 47714 | United States |
| Teva Investigational Site 133 | Lenexa | Kansas | 66214 | United States |
| Teva Investigational Site 135 | Brockton | Massachusetts | 02301 | United States |
| Teva Investigational Site 124 | New Bedford | Massachusetts | 02740 | United States |
| Teva Investigational Site 151 | Springfield | Massachusetts | 01104 | United States |
| Teva Investigational Site 109 | Watertown | Massachusetts | 02472 | United States |
| Teva Investigational Site 115 | Worcester | Massachusetts | 01605 | United States |
| Teva Investigational Site 110 | Ann Arbor | Michigan | 48104 | United States |
| Teva Investigational Site 114 | Kalamazoo | Michigan | 49009 | United States |
| Teva Investigational Site 150 | Golden Valley | Minnesota | 55422 | United States |
| Teva Investigational Site 152 | Kansas City | Missouri | 64114 | United States |
| Teva Investigational Site 107 | Springfield | Missouri | 65807 | United States |
| Teva Investigational Site 104 | St Louis | Missouri | 63141 | United States |
| Teva Investigational Site 148 | Reno | Nevada | 89502 | United States |
| Teva Investigational Site 105 | The Bronx | New York | 10461 | United States |
| Teva Investigational Site 131 | Greensboro | North Carolina | 27405-6962 | United States |
| Teva Investigational Site 118 | Raleigh | North Carolina | 27607 | United States |
| Teva Investigational Site 168 | Winston-Salem | North Carolina | 27103 | United States |
| Teva Investigational Site 122 | Canton | Ohio | 44718 | United States |
| Teva Investigational Site 141 | Cincinnati | Ohio | 45227 | United States |
| Teva Investigational Site 142 | Cincinnati | Ohio | 45229-3039 | United States |
| Teva Investigational Site 155 | Cleveland | Ohio | 44195 | United States |
| Teva Investigational Site 102 | Columbus | Ohio | 43221 | United States |
| Teva Investigational Site 127 | Oklahoma City | Oklahoma | 73112 | United States |
| Teva Investigational Site 111 | Philadelphia | Pennsylvania | 19107 | United States |
| Teva Investigational Site 120 | Goose Creek | South Carolina | 29445 | United States |
| Teva Investigational Site 153 | Bristol | Tennessee | 37620 | United States |
| Teva Investigational Site 126 | Memphis | Tennessee | 38119 | United States |
| Teva Investigational Site 154 | Nashville | Tennessee | 37203 | United States |
| Teva Investigational Site 128 | Arlington | Texas | 76012 | United States |
| Teva Investigational Site 121 | Austin | Texas | 78731 | United States |
| Teva Investigational Site 136 | Austin | Texas | 78745 | United States |
| Teva Investigational Site 123 | Charlottesville | Virginia | 22911 | United States |
| Teva Investigational Site 144 | Roanoke | Virginia | 24018 | United States |
| 28862758 | Derived | Cohen JM, Dodick DW, Yang R, Newman LC, Li T, Aycardi E, Bigal ME. Fremanezumab as Add-On Treatment for Patients Treated With Other Migraine Preventive Medicines. Headache. 2017 Oct;57(9):1375-1384. doi: 10.1111/head.13156. Epub 2017 Sep 1. |
| 26432181 | Derived | Bigal ME, Edvinsson L, Rapoport AM, Lipton RB, Spierings EL, Diener HC, Burstein R, Loupe PS, Ma Y, Yang R, Silberstein SD. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015 Nov;14(11):1091-100. doi: 10.1016/S1474-4422(15)00245-8. Epub 2015 Sep 30. |
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
| FG002 | LBR-101 High Dose | Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). |
|
| Safety Analysis Set | Safety set: all participants who received at least one dose of study drug |
|
| Intent-to-treat (ITT) | All participants evaluable for efficacy |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received subcutaneous placebo injections at one visit per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). |
| BG001 | LBR-101 Low Dose | Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8). |
| BG002 | LBR-101 High Dose | Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). |
| BG003 | 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 |
| ||||||||||||||||
| Years of migraine | Mean | Standard Deviation | Years |
| |||||||||||||||
| Preventive Medication Use | Participants reported preventive migraine medication use at the time of randomization | Count of Participants | Participants |
|
| 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 | Mean Change From Baseline in the Number of Monthly Cumulative Headache Hours of Any Severity on Headache Days Relative to the 28-day Post-treatment Period Ending With Week 12 | A headache 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 of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of hours with headache of any severity during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe. | Intent-to-treat (ITT) population includes all randomized participants who received at least one dose of study drug and obtained at least one endpoint measurement. | Posted | Least Squares Mean | Standard Error | Number of monthly headache hours | Baseline to week 12 |
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| Primary | Number of Participants With at Least One Adverse Event | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, 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 the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Safety analysis set included all randomized participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline to week 12 |
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| Secondary | Mean Change From Baseline in the Number of Headache Days of at Least Moderate Severity Relative to the 28-day Post-treatment Period Ending With Week 12 | A headache 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 of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of headache days of at least moderate severity during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe. | Intent-to-treat (ITT) population includes all randomized participants who received at least one dose of study medication and obtained at least one endpoint measurement. | Posted | Least Squares Mean | Standard Error | Number of headache days | Baseline to week 12 |
|
Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received subcutaneous placebo injections at one visit per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). | 0 | 89 | 1 | 89 | 3 | 89 |
| EG001 | LBR-101 Low Dose | Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8). | 0 | 88 | 1 | 88 | 6 | 88 |
| EG002 | LBR-101 High Dose | Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). | 0 | 86 | 2 | 86 | 8 | 86 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Irritable bowel syndrome | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA 17.0 | Systematic Assessment |
|
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. | 1-888-483-8279 | USMedInfo@tevapharm.com |
| ID | Term |
|---|---|
| D006261 | Headache |
| D008881 | Migraine Disorders |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000604315 | fremanezumab |
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| 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 |
|
| No |
|
| 0.0057 |
The threshold for statistical significance was p = .05. |
| Mean Difference (Final Values) |
| -30.41 |
| Standard Error of the Mean |
| 10.90 |
| 2-Sided |
| 95 |
| -51.88 |
| -8.95 |
| Superiority |
| OG002 | LBR-101 High Dose | Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). |
|
|
| OG002 | LBR-101 High Dose | Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8). |
|
|