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

Migraine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04530110
• Other study ID #: TV48125-CNS-30084
• Secondary ID: 2019-002056-16
• Status: Recruiting
• Phase: Phase 3
• Start date: September 16, 2020
• Est. completion date: March 21, 2026

Study information

• Verified date: May 2024
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: Teva U.S. Medical Information
• Phone: 1-888-483-8279
• Email: USMedInfo[@]tevapharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 476
• Est. completion date: March 21, 2026
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

Intervention

Drug:
• Fremanezumab
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.

Locations

Country	Name	City	State
Canada	Teva Investigational Site 11181	Montreal	Quebec
Canada	Teva Investigational Site 11179	Ottawa	Ontario
Canada	Teva Investigational Site 11182	Ottawa	Ontario
Finland	Teva Investigational Site 40053	Helsinki
Finland	Teva Investigational Site 40049	Kuopio
Finland	Teva Investigational Site 40054	Oulu
Finland	Teva Investigational Site 40052	Tampere
Germany	Teva Investigational Site 32728	Bad Homburg
Germany	Teva Investigational Site 32729	Berlin
Germany	Teva Investigational Site 32726	Leipzig
Israel	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
Italy	Teva Investigational Site 30230	Firenze
Italy	Teva Investigational Site 30226	Milano
Italy	Teva Investigational Site 30228	Milano
Italy	Teva Investigational Site 30239	Milano
Italy	Teva Investigational Site 30238	Padua
Italy	Teva Investigational Site 30227	Pavia
Italy	Teva Investigational Site 30225	Rome
Netherlands	Teva Investigational Site 38138	Doetinchem
Netherlands	Teva Investigational Site 38135	Nijmegen
Netherlands	Teva Investigational Site 38136	Rotterdam
Poland	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
Spain	Teva Investigational Site 31271	Barcelona
Spain	Teva Investigational Site 31270	Valencia
Spain	Teva Investigational Site 31265	Valladolid
United States	Teva Investigational Site 14276	Amherst	New York
United States	Teva Investigational Site 14251	Ann Arbor	Michigan
United States	Teva Investigational Site 14243	Atlanta	Georgia
United States	Teva Investigational Site 14319	Aurora	Colorado
United States	Teva Investigational Site 14252	Austin	Texas
United States	Teva Investigational Site 14273	Austin	Texas
United States	Teva Investigational Site 14365	Baltimore	Maryland
United States	Teva Investigational Site 14256	Bridgeton	Missouri
United States	Teva Investigational Site 14374	Bristol	Tennessee
United States	Teva Investigational Site 14264	Cincinnati	Ohio
United States	Teva Investigational Site 14368	Colorado Springs	Colorado
United States	Teva Investigational Site 14360	Covington	Louisiana
United States	Teva Investigational Site 14367	Dallas	Texas
United States	Teva Investigational Site 14377	Durham	North Carolina
United States	Teva Investigational Site 14263	Hoffman Estates	Illinois
United States	Teva Investigational Site 14244	Jacksonville	Florida
United States	Teva Investigational Site 14327	Louisville	Kentucky
United States	Teva Investigational Site 14325	Miami	Florida
United States	Teva Investigational Site 14270	Minneapolis	Minnesota
United States	Teva Investigational Site 14371	New Brunswick	New Jersey
United States	Teva Investigational Site 14323	Norfolk	Virginia
United States	Teva Investigational Site 14257	Oklahoma City	Oklahoma
United States	Teva Investigational Site 14364	Philadelphia	Pennsylvania
United States	Teva Investigational Site 14248	Raleigh	North Carolina
United States	Teva Investigational Site 14376	Ridgeland	Mississippi
United States	Teva Investigational Site 14375	Salt Lake City	Utah
United States	Teva Investigational Site 14258	Savannah	Georgia
United States	Teva Investigational Site 14363	Tulsa	Oklahoma
United States	Teva Investigational Site 14246	Waltham	Massachusetts
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 14245	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Finland,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events	including local injection site reaction/pain	Day 1 - Day 393
Primary	Incidence of participants with clinically significant changes in laboratory values		Day 1 - Day 253
Primary	Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings		Day 1 - Day 253
Primary	Incidence of abnormal vital signs	(systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements	Day 1 - Day 253
Primary	Incidence of abnormal physical examination findings		Day 1- Day 393
Primary	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	Mean change in the number of headache days of at least moderate severity		Day 1 - Day 253
Secondary	Mean change in the number of migraine days		Day 1 - Day 253
Secondary	Proportion of participants reaching at least 50% reduction in the number of migraine days		Day 1 - Day 253
Secondary	Proportion of participants reaching at least 50% reduction in the number of headache days of at least moderate severity		Day 1 - Day 253
Secondary	Mean change in the number of days of use of any acute headache medications		Day 1 - Day 253
Secondary	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
Secondary	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