A Study to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents
- Registration Number
- NCT04530110
- Lead Sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Brief Summary
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
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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 476
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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Fremanezumab Fremanezumab The dose of Fremanezumab to be administered will be confirmed or adjusted, as appropriate, based on the participant's weight every 3 months.
- Primary Outcome Measures
Name Time Method Incidence of participants with clinically significant changes in laboratory values Day 1 - Day 253 Incidence of abnormal physical examination findings Day 1- Day 393 Incidence of abnormal vital signs Day 1 - Day 253 (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements
Incidence of adverse events Day 1 - Day 393 including local injection site reaction/pain
Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings Day 1 - Day 253 Yes/No suicidality ideation Day 1 - Day 393 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.
- Secondary Outcome Measures
Name Time Method Proportion of participants developing antidrug antibodies (ADAs) throughout the study Day 1 - Day 393 The impact of ADAs on safety and efficacy will be analyzed if the number of ADA-positive participants allows.
Mean change in the number of headache days of at least moderate severity 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 migraine days Day 1 - Day 253 Mean change in the PedMIDAS questionnaire score Day 1 - Day 393 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.
Mean change in the number of days of use of any acute headache medications Day 1 - Day 253
Trial Locations
- Locations (70)
Teva Investigational Site 30230
🇮🇹Firenze, Italy
Teva Investigational Site 30239
🇮🇹Milano, Italy
Teva Investigational Site 30228
🇮🇹Milano, Italy
Teva Investigational Site 30226
🇮🇹Milano, Italy
Teva Investigational Site 30238
🇮🇹Padua, Italy
Teva Investigational Site 30227
🇮🇹Pavia, Italy
Teva Investigational Site 30225
🇮🇹Rome, Italy
Teva Investigational Site 38138
🇳🇱Doetinchem, Netherlands
Teva Investigational Site 38135
🇳🇱Nijmegen, Netherlands
Teva Investigational Site 38136
🇳🇱Rotterdam, Netherlands
Teva Investigational Site 53441
🇵🇱Gdansk, Poland
Teva Investigational Site 53437
🇵🇱Kielce, Poland
Teva Investigational Site 53443
🇵🇱Krakow, Poland
Teva Investigational Site 53452
🇵🇱Krakow, Poland
Teva Investigational Site 53440
🇵🇱Lublin, Poland
Teva Investigational Site 53439
🇵🇱Poznan, Poland
Teva Investigational Site 53451
🇵🇱Poznan, Poland
Teva Investigational Site 53442
🇵🇱Szczecin, Poland
Teva Investigational Site 31271
🇪🇸Barcelona, Spain
Teva Investigational Site 31270
🇪🇸Valencia, Spain
Teva Investigational Site 31265
🇪🇸Valladolid, Spain
Teva Investigational Site 14319
🇺🇸Aurora, Colorado, United States
Teva Investigational Site 14368
🇺🇸Colorado Springs, Colorado, United States
Teva Investigational Site 14244
🇺🇸Jacksonville, Florida, United States
Teva Investigational Site 14325
🇺🇸Miami, Florida, United States
Teva Investigational Site 14250
🇺🇸West Palm Beach, Florida, United States
Teva Investigational Site 14255
🇺🇸West Palm Beach, Florida, United States
Teva Investigational Site 14243
🇺🇸Atlanta, Georgia, United States
Teva Investigational Site 14258
🇺🇸Savannah, Georgia, United States
Teva Investigational Site 14263
🇺🇸Hoffman Estates, Illinois, United States
Teva Investigational Site 14245
🇺🇸Wichita, Kansas, United States
Teva Investigational Site 14327
🇺🇸Louisville, Kentucky, United States
Teva Investigational Site 14360
🇺🇸Covington, Louisiana, United States
Teva Investigational Site 14365
🇺🇸Baltimore, Maryland, United States
Teva Investigational Site 14246
🇺🇸Waltham, Massachusetts, United States
Teva Investigational Site 14251
🇺🇸Ann Arbor, Michigan, United States
Teva Investigational Site 14270
🇺🇸Minneapolis, Minnesota, United States
Teva Investigational Site 14376
🇺🇸Ridgeland, Mississippi, United States
Teva Investigational Site 14256
🇺🇸Bridgeton, Missouri, United States
Teva Investigational Site 14371
🇺🇸New Brunswick, New Jersey, United States
Teva Investigational Site 14276
🇺🇸Amherst, New York, United States
Teva Investigational Site 14377
🇺🇸Durham, North Carolina, United States
Teva Investigational Site 14248
🇺🇸Raleigh, North Carolina, United States
Teva Investigational Site 14264
🇺🇸Cincinnati, Ohio, United States
Teva Investigational Site 14257
🇺🇸Oklahoma City, Oklahoma, United States
Teva Investigational Site 14364
🇺🇸Philadelphia, Pennsylvania, United States
Teva Investigational Site 14363
🇺🇸Tulsa, Oklahoma, United States
Teva Investigational Site 14374
🇺🇸Bristol, Tennessee, United States
Teva Investigational Site 14252
🇺🇸Austin, Texas, United States
Teva Investigational Site 14273
🇺🇸Austin, Texas, United States
Teva Investigational Site 14367
🇺🇸Dallas, Texas, United States
Teva Investigational Site 14375
🇺🇸Salt Lake City, Utah, United States
Teva Investigational Site 14323
🇺🇸Norfolk, Virginia, United States
Teva Investigational Site 11182
🇨🇦Ottawa, Ontario, Canada
Teva Investigational Site 11179
🇨🇦Ottawa, Ontario, Canada
Teva Investigational Site 11181
🇨🇦Montreal, Quebec, Canada
Teva Investigational Site 40053
🇫🇮Helsinki, Finland
Teva Investigational Site 40049
🇫🇮Kuopio, Finland
Teva Investigational Site 40054
🇫🇮Oulu, Finland
Teva Investigational Site 40052
🇫🇮Tampere, Finland
Teva Investigational Site 32728
🇩🇪Bad Homburg, Germany
Teva Investigational Site 32729
🇩🇪Berlin, Germany
Teva Investigational Site 32726
🇩🇪Leipzig, Germany
Teva Investigational Site 80170
🇮🇱Be'er Ya'akov, Israel
Teva Investigational Site 80166
🇮🇱Haifa, Israel
Teva Investigational Site 80168
🇮🇱Holon, Israel
Teva Investigational Site 80169
🇮🇱Jerusalem, Israel
Teva Investigational Site 80167
🇮🇱Ramat Gan, Israel
Teva Investigational Site 80164
🇮🇱Safed, Israel
Teva Investigational Site 80165
🇮🇱Tel-Aviv, Israel