A Study to Test if Fremanezumab is Effective in Preventing Episodic Migraine in Patients 6 to 17 Years of Age

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of fremanezumab as compared to placebo for the preventive treatment of episodic migraine (EM). Secondary objectives are to further demonstrate the efficacy of Fremanezumab as compared to placebo for the preventive treatment of EM, to evaluate the safety and tolerability of Fremanezumab in the preventive treatment of EM and to evaluate the immunogenicity of Fremanezumab and the impact of antidrug antibodies (ADAs) on clinical outcomes in participants exposed to Fremanezumab. The total duration of the study is planned to be up to 51 months.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Episodic Migraine in Pediatric Patients 6 to 17 Years of Age

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 clinical history of recurrent headache consistent with the diagnosis of migraine for at least 6 months before screening, consistent with ICHD-3 criteria (Headache Classification Committee of the IHS 2013), and a history of ≤=14 headache days per month in each of the 3 months prior to screening (visit 1). The participant or parent/caregiver maintain a prospectively collected headache diary The participant does not have chronic daily headache. For the purposes of this study, chronic daily headache is operationally defined as <4 headache-free days during the 28-day baseline period. NOTE: Additional criteria apply; please contact the investigator for more information. Exclusion Criteria: The participant is using medications containing opioids (including codeine) or barbiturates (including Fiorinal®, Fioricet®, or any other combination containing butalbital) for the treatment of migraine during the 3 months prior to the day of the screening visit. The participant or parent/caregiver maintain a prospectively collected headache diary The participant has used an intervention/device (eg, scheduled nerve block or transcranial magnetic stimulation) for the treatment of migraine or in the head or neck area for any condition during the 2 months prior to the day of the screening visit. The participant has a current history of a clinically significant psychiatric condition, at the discretion of the investigator. Any prior history of a suicide attempt, or a history of suicidal ideation with a specific plan within the past 2 years, must be excluded. The participant has an ongoing infection or a known history of human immunodeficiency virus infection, tuberculosis, Lyme disease, or chronic hepatitis B or C, or a known active infection of coronavirus disease 2019 (COVID-19). The participant has a past or current history of cancer. The participant is pregnant or nursing. The participant has a history of hypersensitivity reactions to injected proteins, including mAbs, or a history of Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome, or the participant is concomitantly using lamotrigine. The participant received a live attenuated vaccine (eg, intranasal flu vaccine, and measles, mumps, and rubella vaccine) within the 12-week period prior to screening. Note: If a medical need arises during the study, the participant may receive a live attenuated vaccine. The participant has a current or past medical history of hemiplegic migraine. NOTE: Additional criteria apply; please contact the investigator for more information.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fremanezumab<br>Participants weighing ≥ threshold will receive Dose A subcutaneously monthly, for 3 months. Participants weighing < threshold will receive Dose B subcutaneously monthly, for 3 months. | Drug: Fremanezumab<br>* Dose A or Dose B subcutaneous<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the monthly average number of migraine days after the first dose of study drug |  | Baseline - Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | including local injection site reaction/pain | Baseline - Month 3 | 
| Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings |  | Baseline - Month 3 | 
| Incidence of abnormal vital signs | (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements | Baseline - Month 3 | 
| Number of participants with clinically significant changes in laboratory values |  | Baseline, Month 1, and Month 3 | 
| Incidence of abnormal physical examination findings |  | Baseline - Month 3 | 
| Yes/No suicidality ideation | Columbia-Suicide Severity Rating Scale (C-SSRS) The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Scale range: Yes or No response to 10 questions, with minimum to maximum range of 0 to 10. Lower score represents better outcomes. | Screening - Month 3 | 
| Mean change in monthly average number of headache days of at least moderate severity after the first dose of study drug |  | Baseline - Month 3 | 
| Proportion of participants reaching at least 50% reduction in the monthly average number of migraine days after the first dose of study drug |  | Baseline - Month 3 | 
| Mean change in the monthly average number of days of use of any acute headache medications after the first dose of study drug |  | Baseline - Month 3 | 
| Mean change in the PedMIDAS questionnaire after administration of the first dose of study drug | The Pediatric Migraine Disability Assessment (PedMIDAS) is used to assess migraine disability across multiple domains of functioning including school, home, social, and recreational. The measure consists of 6 items measuring the number of days in which activities were missed as a result of headache/migraine. The measure yields a total score by summing items. Total scores correspond to one of four disability grades: 0-10 = little to no disability, 11-30 = mild disability, 31-50 = moderate disability, and >50 = severe disability. | Baseline and Month 3 | 
| Mean change PedsQL after administration of the first dose of study drug | Pediatric Quality of Life Inventory (PedsQL) A health-related quality-of-life instrument that consists of a well-validated generic core measure and some condition and disease-specific modules. The instructions ask how much of a problem each item has been during the past 1 month. A 5-point response scale is utilized across child self-report and parent proxy report as follows: 0=never a problem; almost never a problem; sometimes a problem; often a problem; almost always a problem. | Baseline - Month 3 | 
| Proportion of participants developing antidrug antibodies (ADAs) throughout the study | The impact of ADAs on safety and efficacy will be analyzed if the number of ADA-positive participants allows. | Baseline - Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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episodic migraine