A Study to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the long-term safety and tolerability of subcutaneous fremanezumab in the preventive treatment of migraine in pediatric participants 6 to 17 years of age (inclusive at enrollment in the pivotal study). Secondary objectives are to evaluate the efficacy of subcutaneous fremanezumab in pediatric participants with migraine and to evaluate the immunogenicity of fremanezumab and the impact of ADAs on clinical outcomes in pediatric participants exposed to fremanezumab. The total duration of the study is planned to be up to 84 months.

Detailed Description
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The study population will be composed of 3 subgroups of participants as follows: Participants rolling over from the pivotal Phase 3 pediatric efficacy studies (Studies TV48125-CNS-30082 and TV48125-CNS-30083) Participants rolling over from the Phase 1 pediatric pharmacokinetic study (Study TV48125-CNS-10141) Participants rolling over from the pivotal Phase 3 pediatric efficacy studies (Studies TV48125-CNS-30082 and TV48125-CNS-30083) for safety follow-up and antidrug antibody (ADA) evaluation only

Official Title
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A Multicenter, Open-Label Study Evaluating the Long-Term Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of Fremanezumab for the Preventive Treatment of Episodic and Chronic Migraine in Pediatric Patients 6 to 17 Years of Age

Conditions
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Migraine

Intervention / Treatment
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* Drug: Fremanezumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 or TV48125-CNS-30083): Participants have completed the pivotal efficacy study and, in the opinion of the Investigator or the Sponsor, are able to complete the study in a safe and compliant way. Participants may continue with a stable dose/regimen of the preventive medication they were taking during the pivotal efficacy studies. The participant continues to meet appropriate criteria carried forward from the pivotal efficacy study/ The participant has received all recommended age-appropriate vaccines according to local standard of care and schedule. The participant weighs at least 17.0 kg on the day of study enrollment. NOTE: Additional criteria apply; please contact the investigator for more information. Inclusion Criteria for Participants Rolling Over from the Phase 1 Pediatric Pharmacokinetic Study (Study TV48125-CNS-10141): The participant/caregiver has demonstrated compliance with the electronic headache diary during the 28-day baseline period by entry of headache data on a minimum of 21 out of 28 days (approximately 75% diary compliance). The participant has received all recommended age-appropriate vaccines according to local standard of care and schedule. The participant weighs at least 17.0 kg on the day of study enrollment. The participant has a body mass index ranging from the 5th to 120% of the 95th percentile, inclusive, on the day of study enrollment. Not using preventive medications or using no more than 2 preventive medications for migraine or other medical condition, as long as the dose and regimen have been stable for at least 2 months prior to screening (visit 1). NOTE: Additional criteria apply; please contact the investigator for more information. Inclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 and TV48125-CNS-30083) for Safety and antidrug antibody (ADA) Assessment Only: • Participants may be included in this study if they sign and date the informed consent document or upon consent of a parent or guardian, if the participant is younger than the age of consent, accompanied by assent of the participant. Exclusion Criteria: Exclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 or TV48125-CNS-30083): In the judgment of the investigator, the participant has a clinically significant abnormal finding on study entry, including hematology, blood chemistry, coagulation tests, or urinalysis values/findings (abnormal tests may be repeated for confirmation). 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 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 is pregnant or nursing. In the judgment of the investigator, the participant has an abnormal finding on the baseline 12-lead ECG considered clinically significant. The participant has a current or past medical history of hemiplegic migraine. NOTE: Additional criteria apply; please contact the investigator for more information. Exclusion Criteria for Participants Rolling Over from the Phase 1 Pharmacokinetic Study (TV48125-CNS-10141): The participant has any clinically significant cardiovascular (including congenital cardiac anomalies or thromboembolic events), endocrine, gastrointestinal, genitourinary, hematologic, hepatic, immunologic, neurologic, ophthalmic, pulmonary, renal disease, or complications of an infection, at the discretion of the investigator. The participant has a current history of a clinically significant psychiatric condition, any prior history of a suicide attempt, or a history of suicidal ideation with a specific plan within the past 2 years, at the discretion of the investigator. 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 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 is pregnant or nursing. In the judgment of the investigator, the participant has an abnormal finding on the baseline 12-lead ECG considered clinically significant. The participant has a current or past medical history of hemiplegic migraine. NOTE: Additional criteria apply; please contact the investigator for more information. Exclusion Criteria for Participants Rolling Over from the Pivotal Efficacy Studies (TV48125-CNS-30082 and TV48125-CNS-30083) for Safety and antidrug antibody (ADA) Assessment Only: Not Applicable

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fremanezumab<br>The dose of Fremanezumab to be administered will be confirmed or adjusted, as appropriate, based on the participant's weight every 3 months. | Drug: Fremanezumab<br>* Participants weighing ≥ threshold will receive Dose A subcutaneously monthly. Participants weighing < threshold will receive Dose B subcutaneously monthly. Subcutaneously monthly, confirmed or adjusted, as appropriate, based on the participant's weight every 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | including local injection site reaction/pain | Day 1 - Day 393 | 
| Incidence of participants with clinically significant changes in laboratory values |  | Day 1 - Day 253 | 
| Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings |  | Day 1 - Day 253 | 
| Incidence of abnormal vital signs | (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements | Day 1 - Day 253 | 
| Incidence of abnormal physical examination findings |  | Day 1- Day 393 | 
| 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. | Day 1 - Day 393 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the number of headache days of at least moderate severity |  | Day 1 - Day 253 | 
| Mean change in the number of migraine days |  | Day 1 - Day 253 | 
| Proportion of participants reaching at least 50% reduction in the number of migraine days |  | Day 1 - Day 253 | 
| Proportion of participants reaching at least 50% reduction in the number of headache days of at least moderate severity |  | Day 1 - Day 253 | 
| Mean change in the number of days of use of any acute headache medications |  | Day 1 - Day 253 | 
| Mean change in the PedMIDAS questionnaire score | 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. | Day 1 - Day 393 | 
| 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. | Day 1 - Day 393 | 

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