A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Period on Efficacy and Safety of Fremanezumab in Chinese Adults With Migraine
- Registration Number
- NCT05458011
- Lead Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 365
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fremanezumab Monthly Fremanezumab Double Blind (DB) Period: Participants will receive fremanezumab once a month (approximately every 4 weeks). Participants will receive a single injection of fremanezumab and two placebo injections on Day 1, and a single injection of fremanezumab on Days 29 and 57. Open Label (OL) Period: Participants will receive fremanezumab once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. Fremanezumab Quarterly Fremanezumab DB Period: Participants will receive fremanezumab once a quarter (once at the beginning of the 12-week double-blind treatment period). Participants will receive 3 injections of fremanezumab on Day 1, and a single placebo injection on Days 29 and 57. OL Period: Participants will receive fremanezumab once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. Placebo Placebo DB Period: Participants will receive placebo once a month (approximately every 4 weeks). Participants will receive 3 placebo injections on Day 1, and a single injection of placebo on Days 29 and 57. OL Period: Participants will receive fremanezumab once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. Fremanezumab Monthly Placebo Double Blind (DB) Period: Participants will receive fremanezumab once a month (approximately every 4 weeks). Participants will receive a single injection of fremanezumab and two placebo injections on Day 1, and a single injection of fremanezumab on Days 29 and 57. Open Label (OL) Period: Participants will receive fremanezumab once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141. Fremanezumab Quarterly Placebo DB Period: Participants will receive fremanezumab once a quarter (once at the beginning of the 12-week double-blind treatment period). Participants will receive 3 injections of fremanezumab on Day 1, and a single placebo injection on Days 29 and 57. OL Period: Participants will receive fremanezumab once a month (approximately every 4 weeks) administered as a single injection on Days 85, 113, and 141.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
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
Trial Locations
- Locations (29)
Teva Investigational Site 88022
🇨🇳Changsha Shi, China
Teva Investigational Site 88015
🇨🇳Suzhou Shi, China
Teva Investigational Site 88023
🇨🇳Tianjin Shi, China
Teva Investigational Site 88008
🇨🇳Changchun, China
Teva Investigational Site 88013
🇨🇳Guiyang, China
Teva Investigational Site 88010
🇨🇳Lianyungang, China
Teva Investigational Site 88001
🇨🇳Beijing, China
Teva Investigational Site 88028
🇨🇳Baotou Shi, China
Teva Investigational Site 88004
🇨🇳Beijing Shi, China
Teva Investigational Site 88009
🇨🇳Changchun, China
Teva Investigational Site 88003
🇨🇳Chengdu Shi, China
Teva Investigational Site 88029
🇨🇳Chongqing, China
Teva Investigational Site 88030
🇨🇳Changsha Shi, China
Teva Investigational Site 88020
🇨🇳Guangzhou Shi, China
Teva Investigational Site 88019
🇨🇳Fuzhou, China
Teva Investigational Site 88033
🇨🇳Rizhao, China
Teva Investigational Site 88005
🇨🇳Luoyang, China
Teva Investigational Site 88026
🇨🇳Harbin Shi, China
Teva Investigational Site 88021
🇨🇳Shanghaishi, China
Teva Investigational Site 88025
🇨🇳Shanghaishi, China
Teva Investigational Site 88016
🇨🇳Shenyang Shi, China
Teva Investigational Site 88011
🇨🇳Shijiazhuang Shi, China
Teva Investigational Site 88024
🇨🇳Tianjin Shi, China
Teva Investigational Site 88012
🇨🇳Wuhan Shi, China
Teva Investigational Site 88017
🇨🇳Wenzhou, China
Teva Investigational Site 88031
🇨🇳Zhanjiang, China
Teva Investigational Site 88006
🇨🇳Wuhan Shi, China
Teva Investigational Site 88032
🇨🇳Xining Shi, China
Teva Investigational Site 88034
🇨🇳Zhengzhou Shi, China