Migraine
Conditions
Brief summary
Primary Objective: To demonstrate the efficacy of fremanezumab administered as monthly and quarterly subcutaneous (sc) injections to adult Chinese participants with migraine. Secondary Objectives: * To further demonstrate the efficacy of fremanezumab administered as monthly and quarterly sc injections. * To evaluate the safety and tolerability of fremanezumab administered as monthly and quarterly sc injections.
Detailed description
The total study duration for participants is planned to be approximately 9 months. The study will consist of a screening visit, a baseline period (4 weeks), a 12-week double-blind treatment period, a 12-week open-label treatment period, and a follow-up period lasting approximately 3 months after the last dose of treatment.
Interventions
DRUGFremanezumab
Pharmaceutical form: solution for injection Route of administration: subcutaneous injection
DRUGPlacebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous injection
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The participant has a diagnosis of migraine with onset at ≤50 years of age. * The participant has a body weight ≥45 kg and body mass index within the range 17.5 to 34.9 kg/m2 (inclusive). * The participant has a history of migraine for ≥12 months prior to screening. * Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is; no vasectomy) must use highly effective birth control methods for the duration of the study and for 6.0 months after discontinuation of investigational medicinal product (IMP). * Men must be sterile or, if they are potentially fertile/reproductively competent (not congenitally sterile) and their female partners are of childbearing potential, should use highly effective birth control for the duration of the study. * Additional criteria apply, please contact the investigator for more information.
Exclusion criteria
* Use of medications containing opioids (including codeine), barbiturates (including butalbital), or any combination product containing opioids or barbiturates (including butalbital) on more than 4 days during the screening period for the treatment of migraine or for any other reason. * Has used an intervention/device (eg, scheduled nerve blocks or transcranial magnetic stimulation) for migraine, or in the head or neck area, during the 2 months prior to screening (visit 1). * History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological \[eg, cerebral ischemia\], or peripheral extremity ischemia or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events), such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism. * History of human immunodeficiency virus, tuberculosis, Lyme disease, or a known or suspected active infection of coronavirus disease 2019 (COVID-19). * Known current infection or history of infection in the past 6 months with hepatitis B or C viruses. * History of cancer in the past 5 years, except for appropriately treated non-melanoma skin carcinoma. * History of hypersensitivity reactions to injected proteins, including monoclonal antibodies (mAbs), or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome, or is concomitantly using lamotrigine. * Any clinically significant uncontrolled medical condition (treated or untreated). * History of alcohol or drug abuse during the past 2 years or drug dependence during the past 5 years. * Additional criteria apply, please contact the investigator for more information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double Blind (DB) Period: Mean Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | Baseline (Day -28 to Day -1), up to Week 12 | A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for migraine with or without aura or; a calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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). 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DB Period: Mean Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab | Baseline (Day -28 to Day -1), Up to Week 12 | Participants recorded any headache medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken each day in their electronic headache diary device. Acute headache medication included opioids, barbiturates, triptans, ergots, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen and their combination products. 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 Period: Number of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | Baseline (Day -28 to Day-1), Up to Week 12 | A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for migraine with or without aura or; a calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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). 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 Period: Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab | Baseline (Day -28 to Day -1), Up to Week 12 | A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of headache of at least moderate severity; or a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). 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 Period: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | Week 0 up to Week 12 | 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| DB Period: Number of Participants Who Did Not Complete the Study Due to AEs | Week 0 up to Week 12 | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| DB Period: Mean Change From Baseline in the Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab | Baseline (Day -28 to Day -1), Up to Week 4 | A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for migraine with or without aura or; a calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 4-week period/number of days with assessments recorded in e-diary for 4-week period) \* 28. |
| OL Period: Number of Participants Who Did Not Complete the Study Due to AEs | Week 12 up to Week 24 | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| DB Period: Number of Participants Who Received Concomitant Medications for AEs | Week 0 up to Week 12 | Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the case report form (CRF). Concomitant medications included: butalbital for migraine/headache, ergots for migraine/headache, NSAIDs for migraine/headache, NSAIDs for other reason than migraine/headache, opioids for migraine/headache, opioids for reasons other reason than migraine/headache, preventive medication as specified in the protocol for migraine/headache, preventive medication as specified in the protocol for other reason than migraine/headache, triptans for migraine/headache. |
| OL Period: Number of Participants Who Received Concomitant Medications for AEs | Week 12 up to Week 24 | Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the case report form (CRF). Concomitant medications included: butalbital for migraine/headache, ergots for migraine/headache, NSAIDs for migraine/headache, NSAIDs for other reason than migraine/headache, opioids for migraine/headache, opioids for reasons other reason than migraine/headache, preventive medication as specified in the protocol for migraine/headache, preventive medication as specified in the protocol for other reason than migraine/headache, triptans for migraine/headache. |
| Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADA) | Day 1 up to Day 225 | — |
| Number of Participants With Treatment-Emergent Neutralizing Antibodies (NAbs) | Day 1 up to Day 225 | — |
| OL Period: Number of Participants With at Least One TEAE | Week 12 up to Week 24 | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Countries
China
Participant flow
Pre-assignment details
A total of 454 participants were screened; of which 365 participants were randomized and included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Placebo DB Period: Participants received placebo SC once a month (approximately every 4 weeks). Participants received 3 placebo injections on Day 1, and a single injection of placebo on Days 29 and 57.
OL Period: Participants received fremanezumab SC once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. | 183 |
| Fremanezumab Monthly DB Period: Participants received fremanezumab SC once a month (approximately every 4 weeks). Participants received a single injection of fremanezumab and two placebo injections on Day 1, and a single injection of fremanezumab on Days 29 and 57.
OL Period: Participants received fremanezumab SC once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. | 91 |
| Fremanezumab Quarterly DB Period: Participants received fremanezumab SC once a quarter (once at the beginning of the 12-week DB treatment period). Participants received 3 injections of fremanezumab on Day 1, and a single placebo injection on Days 29 and 57.
OL Period: Participants received fremanezumab SC once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. | 91 |
| Total | 365 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| DB Period (12 Weeks) | Adverse Event | 2 | 1 | 1 |
| DB Period (12 Weeks) | Non-compliance with trial drug | 0 | 0 | 1 |
| DB Period (12 Weeks) | Protocol deviation | 0 | 2 | 2 |
| DB Period (12 Weeks) | Withdrawal by Subject | 4 | 1 | 1 |
| OL Period (12 Weeks) | Adverse Event | 1 | 2 | 1 |
| OL Period (12 Weeks) | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo | Fremanezumab Monthly | Fremanezumab Quarterly | Total |
|---|---|---|---|---|
| Age, Continuous | 38.8 years STANDARD_DEVIATION 10.03 | 38.6 years STANDARD_DEVIATION 9.42 | 39.7 years STANDARD_DEVIATION 10.89 | 38.9 years STANDARD_DEVIATION 10.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 183 Participants | 91 Participants | 90 Participants | 364 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Number of Migraine Days | 11.0 days STANDARD_DEVIATION 4.96 | 10.4 days STANDARD_DEVIATION 5.94 | 10.4 days STANDARD_DEVIATION 5.2 | 10.7 days STANDARD_DEVIATION 5.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 183 Participants | 91 Participants | 91 Participants | 365 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 142 Participants | 71 Participants | 73 Participants | 286 Participants |
| Sex: Female, Male Male | 41 Participants | 20 Participants | 18 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 183 | 0 / 91 | 0 / 91 | 0 / 175 | 0 / 86 | 0 / 85 |
| other Total, other adverse events | 30 / 183 | 23 / 91 | 15 / 91 | 33 / 175 | 23 / 86 | 16 / 85 |
| serious Total, serious adverse events | 1 / 183 | 2 / 91 | 0 / 91 | 0 / 175 | 2 / 86 | 2 / 85 |
Outcome results
Primary
Double Blind (DB) Period: Mean Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab
A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for migraine with or without aura or; a calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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). 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).
Time frame: Baseline (Day -28 to Day -1), up to Week 12
Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Double Blind (DB) Period: Mean Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | -2.8 days/month | Standard Error 0.48 |
| Fremanezumab Monthly/Quarterly | Double Blind (DB) Period: Mean Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | -4.6 days/month | Standard Error 0.48 |
p-value: <0.000195% CI: [-2.66, -0.95]ANCOVA
Secondary
DB Period: Mean Change From Baseline in the Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab
A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for migraine with or without aura or; a calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 4-week period/number of days with assessments recorded in e-diary for 4-week period) \* 28.
Time frame: Baseline (Day -28 to Day -1), Up to Week 4
Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in the Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab | -2.2 days | Standard Error 0.52 |
| Fremanezumab Monthly/Quarterly | DB Period: Mean Change From Baseline in the Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab | -4.5 days | Standard Error 0.52 |
Secondary
DB Period: Mean Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab
Participants recorded any headache medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken each day in their electronic headache diary device. Acute headache medication included opioids, barbiturates, triptans, ergots, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen and their combination products. 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.
Time frame: Baseline (Day -28 to Day -1), Up to Week 12
Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab | -1.1 days/month | Standard Error 0.41 |
| Fremanezumab Monthly/Quarterly | DB Period: Mean Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab | -3.0 days/month | Standard Error 0.41 |
Secondary
DB Period: Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab
A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of headache of at least moderate severity; or a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). 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.
Time frame: Baseline (Day -28 to Day -1), Up to Week 12
Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | DB Period: Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab | -2.4 days/month | Standard Error 0.43 |
| Fremanezumab Monthly/Quarterly | DB Period: Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab | -4.5 days/month | Standard Error 0.43 |
Secondary
DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab
A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for migraine with or without aura or; a calendar day (0:00 to 23:59) demonstrating at least 2 consecutive hours of a headache meeting the criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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). 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.
Time frame: Baseline (Day -28 to Day-1), Up to Week 12
Population: DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. Efficacy analysis was planned to be evaluated combined for both fremanezumab dose treatment groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | 63 Participants |
| Fremanezumab Monthly/Quarterly | DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab | 103 Participants |
Secondary
DB Period: Number of Participants Who Did Not Complete the Study Due to AEs
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Week 0 up to Week 12
Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | DB Period: Number of Participants Who Did Not Complete the Study Due to AEs | 2 Participants |
| Fremanezumab Monthly/Quarterly | DB Period: Number of Participants Who Did Not Complete the Study Due to AEs | 1 Participants |
| DB Period: Fremanezumab Quarterly | DB Period: Number of Participants Who Did Not Complete the Study Due to AEs | 1 Participants |
Secondary
DB Period: Number of Participants Who Received Concomitant Medications for AEs
Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the case report form (CRF). Concomitant medications included: butalbital for migraine/headache, ergots for migraine/headache, NSAIDs for migraine/headache, NSAIDs for other reason than migraine/headache, opioids for migraine/headache, opioids for reasons other reason than migraine/headache, preventive medication as specified in the protocol for migraine/headache, preventive medication as specified in the protocol for other reason than migraine/headache, triptans for migraine/headache.
Time frame: Week 0 up to Week 12
Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | DB Period: Number of Participants Who Received Concomitant Medications for AEs | 51 Participants |
| Fremanezumab Monthly/Quarterly | DB Period: Number of Participants Who Received Concomitant Medications for AEs | 28 Participants |
| DB Period: Fremanezumab Quarterly | DB Period: Number of Participants Who Received Concomitant Medications for AEs | 23 Participants |
Secondary
DB Period: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Week 0 up to Week 12
Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | DB Period: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 79 Participants |
| Fremanezumab Monthly/Quarterly | DB Period: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 48 Participants |
| DB Period: Fremanezumab Quarterly | DB Period: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 37 Participants |
Secondary
Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADA)
Time frame: Day 1 up to Day 225
Population: Participants who received fremanezumab were analyzed for ADA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADA) | 28 Participants |
| Fremanezumab Monthly/Quarterly | Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADA) | 11 Participants |
| DB Period: Fremanezumab Quarterly | Number of Participants With Treatment Emergent Anti-Drug Antibodies (ADA) | 9 Participants |
Secondary
Number of Participants With Treatment-Emergent Neutralizing Antibodies (NAbs)
Time frame: Day 1 up to Day 225
Population: Participants who received fremanezumab were analyzed for ADA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Neutralizing Antibodies (NAbs) | 27 Participants |
| Fremanezumab Monthly/Quarterly | Number of Participants With Treatment-Emergent Neutralizing Antibodies (NAbs) | 11 Participants |
| DB Period: Fremanezumab Quarterly | Number of Participants With Treatment-Emergent Neutralizing Antibodies (NAbs) | 9 Participants |
Secondary
OL Period: Number of Participants Who Did Not Complete the Study Due to AEs
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Week 12 up to Week 24
Population: The OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | OL Period: Number of Participants Who Did Not Complete the Study Due to AEs | 1 Participants |
| Fremanezumab Monthly/Quarterly | OL Period: Number of Participants Who Did Not Complete the Study Due to AEs | 1 Participants |
| DB Period: Fremanezumab Quarterly | OL Period: Number of Participants Who Did Not Complete the Study Due to AEs | 1 Participants |
Secondary
OL Period: Number of Participants Who Received Concomitant Medications for AEs
Concomitant medications included all medications taken while the participant was treated with the study drug. Any concomitant medication received by the participant for AEs was recorded on the case report form (CRF). Concomitant medications included: butalbital for migraine/headache, ergots for migraine/headache, NSAIDs for migraine/headache, NSAIDs for other reason than migraine/headache, opioids for migraine/headache, opioids for reasons other reason than migraine/headache, preventive medication as specified in the protocol for migraine/headache, preventive medication as specified in the protocol for other reason than migraine/headache, triptans for migraine/headache.
Time frame: Week 12 up to Week 24
Population: The OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | OL Period: Number of Participants Who Received Concomitant Medications for AEs | 46 Participants |
| Fremanezumab Monthly/Quarterly | OL Period: Number of Participants Who Received Concomitant Medications for AEs | 26 Participants |
| DB Period: Fremanezumab Quarterly | OL Period: Number of Participants Who Received Concomitant Medications for AEs | 30 Participants |
Secondary
OL Period: Number of Participants With at Least One TEAE
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. TEAEs were defined as AEs that occurred after the first dose of study drug was administered through end of the trial. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Week 12 up to Week 24
Population: The OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | OL Period: Number of Participants With at Least One TEAE | 78 Participants |
| Fremanezumab Monthly/Quarterly | OL Period: Number of Participants With at Least One TEAE | 40 Participants |
| DB Period: Fremanezumab Quarterly | OL Period: Number of Participants With at Least One TEAE | 38 Participants |