A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Period on Efficacy and Safety of Fremanezumab in Chinese Adults With Migraine

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study With an Open-Label Treatment Period of Fremanezumab Administered Subcutaneously Monthly or Quarterly for the Preventive Treatment of Migraine in Adult Chinese Patients

Conditions
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Migraine

Intervention / Treatment
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* Drug: Fremanezumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fremanezumab Monthly<br>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. | Drug: Fremanezumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>* Other names: Ajovy;Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>|
| Experimental: Fremanezumab Quarterly<br>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. | Drug: Fremanezumab<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>* Other names: Ajovy;Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double Blind (DB) Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab |  | Baseline Period (Day -28 to Day -1), Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DB Period: Change From Baseline in the Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab |  | Baseline Period (Day -28 to Day -1), Up to Week 4 | 
| DB Period: 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 Period (Day -28 to Day -1), Up to Week 12 | 
| DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab |  | Baseline Period (Day -28 to Day-1), Up to Week 12 | 
| DB Period: 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 Period (Day -28 to Day -1), Up to Week 12 | 
| Number of Participants Who Experience Adverse Events (AEs) |  | Baseline Visit (Day 1), Up to Week 32 | 
| Number of Participants Who Do Not Complete the Study Due to Adverse Events |  | Up to Week 32 | 
| Number of Participants Who Receive Concomitant Medications |  | Baseline Visit (Day 1), Up to Week 32 | 
| Number of Participants with Treatment Emergent Anti-Drug Antibodies (ADA) |  | Baseline Visit (Day 1), Day 57, Day 169, Day 225 | 
| Assessment of Anti-Drug Antibodies in Plasma Level by Titer |  | Baseline Visit (Day 1), Day 57, Day 169, Day 225 | 
| Assessment of Anti-Drug Antibodies in Plasma Level by Kinetics |  | Baseline Visit (Day 1), Day 57, Day 169, Day 225 | 
| Assessment of Anti-Drug Antibodies in Plasma Level by Neutralizing Activities |  | Baseline Visit (Day 1), Day 57, Day 169, Day 225 |