Episodic Migraine MedDRA version: 20.0 Level: HLT Classification code 10027603 Term: Migraine headaches System Organ Class: 10029205 - Nervous system disorders MedDRA version: 22.0 Level: LLT Classification code 10082019 Term: Episodic migraine System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: AJOVY
Product Name: fremanezumab
Product Code: TEV-48125
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: fremanezumab
CAS Number: 1655501-53-3
Curren
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. The patient is a male or female between the ages of 6 to 17 years (inclusive) on the day of randomization to study drug/IMP. b. The patient’s parent(s) or legal guardian(s) must give written informed consent, and the patient must give assent (in accordance with local regulations). Note: In some countries, patients aged 15 to 17 years (inclusive) may give written informed consent; however, the patient’s parent(s) or legal guardian(s) must be informed, per local regulations. c. The patient has a clinical history of recurrent headache consistent with the diagnosis of migraine for at least 6 months before screening, consistent with the ICHD-3 criteria (Headache Classification Committee of the IHS 2013), and a history of =14 headaches days per month in each of the 3 months prior to screening (visit 1). d. The patient or parent/caregiver has maintained a prospectively collected headache diary during a 28-day baseline period in which at least 4 migraine days and =14 headache days were recorded. Migraine days have at least 1 of the following migraine characteristics: -head pain of moderate to severe intensity lasting for 2 or more hours in duration and accompanied by either throbbing quality, predominantly unilateral location, or aggravation with normal activities. -headache is accompanied by a migraine-associated symptom, such as photophobia, phonophobia, abdominal pain, nausea, or vomiting. -headache is preceded by an aura, as described by ICHD-3 criteria. -headache was treated by a nonsteroidal anti-inflammatory drug (NSAID), paracetamol, triptan, or ergot preparation. e. The patient 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. f. Not using migraine preventive medications or using no more than 2 migraine 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). A list of migraine preventive medications allowed for any condition for the duration of the study for approximately 30% of patients is presented in Appendix C. Note: A person is considered to be not using migraine preventive medications when at least 5 half-lives have passed since the last use of the medication prior to screening (visit 1) or at least 4 months have passed since the last use of Onabotulinium toxin A or B prior to screening (visit 1).The use of other agents that are not included in Appendix C but used for migraine prevention is permitted during the study; however, these patients will not be counted toward the approximately 30% patient limit threshold. g. Females who are postmenarchal or =12 years of age may be included only if they have a negative beta-human chorionic gonadotropin (ß-HCG) test at baseline or are sterile. h. Females who are postmenarchal or =12 years of age and sexually active must use highly effective birth control methods with their male partners for the duration of the study (ie, starting at screening) and for 6 months after the last dose of IMP. Males who are sexually active with female partners must use a condom for the duration of the study and for 6 months after the last administration of IMP. i. The patient/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%
Exclusion criteria
Exclusion criteria: a. The patient 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. b. The patient 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. c. The patient 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. d. The patient 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. e. The patient has an ongoing infection or a known history of human immunodeficiency virus (HIV) infection, tuberculosis, Lyme disease, chronic hepatitis B or C, or a known active infection of COVID-19. f. The patient has a past or current history of cancer. g. The patient is pregnant or nursing. h. The patient 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 patient is concomitantly using lamotrigine. i. The patient has participated in another study of an IMP (or a medical device) within the 30 days (or 90 days for biologics) or 5 half-lives previous to the day of the screening visit (whichever is longer), or is currently participating in another study of an IMP (or a medical device). j. The patient has had exposure to a mAb targeting the CGRP pathway (erenumab, eptinezumab, galcanezumab, fremanezumab) during the 6 months previous to the day of the screening visit. k. Previous participation in the Phase 1 pharmacokinetics study (Study TV48125-CNS-10141). l. In the judgment of the investigator, the patient has an abnormal finding on the baseline 12-lead ECG considered clinically significant. m. In the judgment of the investigator, the patient has a significantly abnormal finding during the 28-day baseline period, including hematology, blood chemistry, coagulation tests, or urinalysis values/findings (abnormal tests may be repeated for confirmation). n. The patient has hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) more than 1.5× the upper limit of normal (ULN) during the 28-day baseline period, after confirmation in a repeat test, or suspected hepatocellular damage that fulfills the criteria for Hy’s law. o. The patient has serum creatinine more than 1.5× the ULN, clinically significant proteinuria (urine dipstick +4), an estimated glomerular filtration rate of <75 mL/min/1.73m2, as calculated by the revised Schwartz formula (eGRF=[0.413k×Ht]/Serum Creatinine), or evidence of renal disease during the 28-day baseline period. p. The patient has any history of alcohol or drug abuse. The definition of alcohol or drug abuse, including marijuana, is based on the investigator's clinical judgment. q. In the judgment of the investigator, the patient cannot full
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of fremanezumab as compared to placebo for the preventive treatment of episodic migraine (EM);Secondary Objective: -To evaluate the safety and tolerability of fremanezumab in the preventive treatment of episodic migraine (EM) -To further demonstrate the efficacy of fremanezumab as compared to placebo for the preventive treatment of episodic migraine (EM) -To evaluate the immunogenicity of fremanezumab and the impact of antidrug antibodies (ADAs) on clinical outcomes in patients exposed to fremanezumab;Primary end point(s): Mean change from baseline (28-day baseline period) in the monthly average number of migraine days during the 12-week period after the first dose of study drug.;Timepoint(s) of evaluation of this end point: 12 weeks after the first dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: -Mean change from baseline (28-day baseline period) in monthly average number of headache days of at least moderate severity during the 12-week period after the first dose of study drug -Proportion of patients reaching at least 50% reduction in the monthly average number of migraine days during the 12 week period after the first dose of study drug -Mean change from baseline (28-day baseline period) in the monthly average number of days of use of any acute headache medications during the 12-week period after the first dose of study drug -Mean change from baseline (day 1) in migraine-related disability score, as measured by the Pediatric Migraine Disability Assessment (PedMIDAS) questionnaire, at 12 weeks after administration of the first dose of study drug -Mean change from baseline (day 1) in quality of life, as measured by the Pediatric Quality of Life Inventory (PedsQL), at 12 weeks after administration of the first dose of study drug -Proportion of patients developing antidrug antibodies (ADAs) throughout the study. The impact of ADAs on safety and efficacy will be analyzed if the number of ADA-positive patients allows. Safety and tolerability endpoints: -Occurrence of adverse events throughout the study, including local injection site reaction/pain -Abnormal standard 12-lead electrocardiogram (ECG) findings -Changes from baseline in vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements -Changes from baseline in clinical laboratory (serum chemistry, hematology, coagulation, and urinalysis) test results -Abnormal physical examination findings -Suicidal ideation and behavior as suggested by the Columbia-Suicide Severity Rating Scale (C-SSRS) ;Timepoint(s) of evaluation of this end point: -Mean change from baseline in monthly average number of migraine days: week 12 after first dose of study drug -Proportion of patients reaching at | — |
Countries
Canada, Finland, Germany, Israel, Italy, Netherlands, Poland, Spain, United States
Contacts
Public ContactClinical Trial Information Desk
Merckle GmbH
Outcome results
None listed