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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Fremanezumab

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

• Study Type: Interventional
• Enrollment (Estimated): 476
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Teva U.S. Medical Information; Phone Number: 1-888-483-8279; Email: USMedInfo@tevapharm.com

Study Locations

• Canada
  • Ontario
    • Nepean, Ontario, Canada, K2G 1W2
      • Completed
      • Teva Investigational Site 11179
    • Ottawa, Ontario, Canada, K1H 8L1
      • Recruiting
      • Teva Investigational Site 11182
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Teva Investigational Site 11181
• Finland
  • Helsinki, Finland, 00380
    • Recruiting
    • Teva Investigational Site 40053
  • Kuopio, Finland, 70210
    • Recruiting
    • Teva Investigational Site 40049
  • Oulu, Finland, 90100
    • Recruiting
    • Teva Investigational Site 40054
  • Tampere, Finland, 33521
    • Recruiting
    • Teva Investigational Site 40052
• Germany
  • Bad Homburg, Germany, 61350
    • Recruiting
    • Teva Investigational Site 32728
  • Berlin, Germany, 13353
    • Recruiting
    • Teva Investigational Site 32729
  • Leipzig, Germany, 04103
    • Recruiting
    • Teva Investigational Site 32726
• Israel
  • Be'er Ya'akov, Israel, 7033001
    • Recruiting
    • Teva Investigational Site 80170
  • Haifa, Israel, 3104802
    • Recruiting
    • Teva Investigational Site 80166
  • Holon, Israel, 58100
    • Recruiting
    • Teva Investigational Site 80168
  • Jerusalem, Israel, 9124001
    • Recruiting
    • Teva Investigational Site 80169
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Teva Investigational Site 80167
  • Safed, Israel, 1311001
    • Recruiting
    • Teva Investigational Site 80164
  • Tel-Aviv, Israel, 6423906
    • Recruiting
    • Teva Investigational Site 80165
• Italy
  • Firenze, Italy, 50139
    • Recruiting
    • Teva Investigational Site 30230
  • Milano, Italy, 20132
    • Recruiting
    • Teva Investigational Site 30239
  • Milano, Italy, 20133
    • Recruiting
    • Teva Investigational Site 30228
  • Milano, Italy, 20148
    • Recruiting
    • Teva Investigational Site 30226
  • Padua, Italy, 35128
    • Recruiting
    • Teva Investigational Site 30238
  • Pavia, Italy, 27100
    • Recruiting
    • Teva Investigational Site 30227
  • Rome, Italy, 00163
    • Recruiting
    • Teva Investigational Site 30225
• Netherlands
  • Doetinchem, Netherlands, 7009 BL
    • Recruiting
    • Teva Investigational Site 38138
  • Nijmegen, Netherlands, 6532 SZ
    • Recruiting
    • Teva Investigational Site 38135
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Teva Investigational Site 38136
• Poland
  • Gdansk, Poland, 80-389
    • Recruiting
    • Teva Investigational Site 53441
  • Kielce, Poland, 25-316
    • Recruiting
    • Teva Investigational Site 53437
  • Krakow, Poland, 30-363
    • Recruiting
    • Teva Investigational Site 53443
  • Krakow, Poland, 30-539
    • Recruiting
    • Teva Investigational Site 53452
  • Lublin, Poland, 20-582
    • Recruiting
    • Teva Investigational Site 53440
  • Poznan, Poland, 60-355
    • Recruiting
    • Teva Investigational Site 53439
  • Poznan, Poland, 61-731
    • Recruiting
    • Teva Investigational Site 53451
  • Szczecin, Poland, 70-111
    • Recruiting
    • Teva Investigational Site 53442
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Teva Investigational Site 31271
  • Valencia, Spain, 46026
    • Completed
    • Teva Investigational Site 31270
  • Valladolid, Spain, 47010
    • Recruiting
    • Teva Investigational Site 31265
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Teva Investigational Site 14319
    • Colorado Springs, Colorado, United States, 80907
      • Recruiting
      • Teva Investigational Site 14368
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Teva Investigational Site 14244
    • Miami, Florida, United States, 33155
      • Recruiting
      • Teva Investigational Site 14325
    • West Palm Beach, Florida, United States, 33407
      • Recruiting
      • Teva Investigational Site 14250
    • West Palm Beach, Florida, United States, 33409
      • Completed
      • Teva Investigational Site 14255
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Completed
      • Teva Investigational Site 14243
    • Savannah, Georgia, United States, 31406
      • Recruiting
      • Teva Investigational Site 14258
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Recruiting
      • Teva Investigational Site 14263
  • Kansas
    • Wichita, Kansas, United States, 67206
      • Recruiting
      • Teva Investigational Site 14245
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Teva Investigational Site 14327
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Recruiting
      • Teva Investigational Site 14360
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • Teva Investigational Site 14365
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Recruiting
      • Teva Investigational Site 14246
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Recruiting
      • Teva Investigational Site 14251
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Completed
      • Teva Investigational Site 14270
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • Recruiting
      • Teva Investigational Site 14376
  • Missouri
    • Bridgeton, Missouri, United States, 63044-2513
      • Completed
      • Teva Investigational Site 14256
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Teva Investigational Site 14371
  • New York
    • Amherst, New York, United States, 14226
      • Recruiting
      • Teva Investigational Site 14276
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Teva Investigational Site 14377
    • Raleigh, North Carolina, United States, 27607
      • Completed
      • Teva Investigational Site 14248
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Recruiting
      • Teva Investigational Site 14264
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Recruiting
      • Teva Investigational Site 14257
    • Tulsa, Oklahoma, United States, 74136
      • Completed
      • Teva Investigational Site 14363
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4318
      • Recruiting
      • Teva Investigational Site 14364
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Recruiting
      • Teva Investigational Site 14374
  • Texas
    • Austin, Texas, United States, 78759
      • Completed
      • Teva Investigational Site 14273
    • Austin, Texas, United States, 78731
      • Recruiting
      • Teva Investigational Site 14252
    • Dallas, Texas, United States, 75235
      • Recruiting
      • Teva Investigational Site 14367
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Recruiting
      • Teva Investigational Site 14375
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Recruiting
      • Teva Investigational Site 14323

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fremanezumab; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): March 21, 2026

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: episodic migraine; chronic migraine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: TV48125-CNS-30084; 2019-002056-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please visit www.clinicalstudydatarequest.com to make your request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No