A Study to Test if Fremanezumab is Effective in Preventing Chronic Migraine in Participants 6 to 17 Years of Age

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Chronic Migraine in Pediatric Patients 6 to 17 Years of Age

The primary objective of the study is to evaluate the effectiveness of fremanezumab as compared to placebo for the preventive treatment of chronic migraine (CM).

Secondary objectives are to further demonstrate the efficacy of Fremanezumab as compared to placebo for the preventive treatment of CM, to evaluate the safety and tolerability of Fremanezumab in the preventive treatment of CM and to evaluate the immunogenicity of Fremanezumab and the impact of antidrug antibodies (ADAs) on clinical outcomes in participants exposed to Fremanezumab

The total duration of the study is planned to be 75 months.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Fremanezumab

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1Z 0M1
      • Teva Investigational Site 11180
    • Ottawa, Ontario, Canada, K1H 8L1
      • Teva Investigational Site 11182
    • Ottawa, Ontario, Canada, K2G 1W2
      • Teva Investigational Site 11179
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Teva Investigational Site 11181
• Finland
  • Helsinki, Finland, 00380
    • Teva Investigational Site 40053
  • Kuopio, Finland, 70210
    • Teva Investigational Site 40049
  • Oulu, Finland, 90100
    • Teva Investigational Site 40054
  • Tampere, Finland, 33521
    • Teva Investigational Site 40052
• Germany
  • Bad Homburg, Germany, 61348
    • Teva Investigational Site 32728
  • Berlin, Germany, 13353
    • Teva Investigational Site 32729
  • Dresden, Germany, 01307
    • Teva Investigational Site 32725
  • Essen, Germany, 452133
    • Teva Investigational Site 32724
  • Leipzig, Germany, 04177
    • Teva Investigational Site 32726
• Israel
  • Be’er Ya‘aqov, Israel, 7033001
    • Teva Investigational Site 80170
  • Haifa, Israel, 3339419
    • Teva Investigational Site 80166
  • Holon, Israel, 58100
    • Teva Investigational Site 80168
  • Jerusalem, Israel, 9124001
    • Teva Investigational Site 80169
  • Ramat Gan, Israel, 5265601
    • Teva Investigational Site 80167
  • Safed, Israel, 1311001
    • Teva Investigational Site 80164
  • Tel Aviv, Israel, 6423906
    • Teva Investigational Site 80165
• Italy
  • Florence, Italy, 50139
    • Teva Investigational Site 30230
  • Milan, Italy, 20132
    • Teva Investigational Site 30239
  • Milan, Italy, 20133
    • Teva Investigational Site 30228
  • Milan, Italy, 20154
    • Teva Investigational Site 30226
  • Padua, Italy, 35128
    • Teva Investigational Site 30238
  • Pavia, Italy, 27100
    • Teva Investigational Site 30227
  • Rome, Italy, 00166
    • Teva Investigational Site 30225
• Netherlands
  • Doetinchem, Netherlands, 7009 BL
    • Teva Investigational Site 38138
  • Nijmegen, Netherlands, 6532 SZ
    • Teva Investigational Site 38135
  • Rotterdam, Netherlands, 3015 GD
    • Teva Investigational Site 38136
• Poland
  • Gdansk, Poland, 80-389
    • Teva Investigational Site 53441
  • Kielce, Poland, 25-316
    • Teva Investigational Site 53437
  • Krakow, Poland, 30-363
    • Teva Investigational Site 53443
  • Krakow, Poland, 30-539
    • Teva Investigational Site 53452
  • Lublin, Poland, 20-582
    • Teva Investigational Site 53440
  • Poznan, Poland, 60-355
    • Teva Investigational Site 53439
  • Poznan, Poland, 61-731
    • Teva Investigational Site 53451
  • Szczecin, Poland, 70-111
    • Teva Investigational Site 53442
• Spain
  • Barcelona, Spain, 08035
    • Teva Investigational Site 31271
  • Elda, Spain, 03600
    • Teva Investigational Site 31266
  • Madrid, Spain, 28007
    • Teva Investigational Site 31268
  • Madrid, Spain, 28046
    • Teva Investigational Site 31267
  • Valencia, Spain, 46026
    • Teva Investigational Site 31270
  • Valladolid, Spain, 47010
    • Teva Investigational Site 31265
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Teva Investigational Site 14281
  • California
    • Banning, California, United States, 92220
      • Teva Investigational Site 14253
    • Loma Linda, California, United States, 92354
      • Teva Investigational Site 14370
    • Los Angeles, California, United States, 90027
      • Teva Investigational Site 14322
    • Sacramento, California, United States, 95815
      • Teva Investigational Site 14361
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Teva Investigational Site 14319
    • Colorado Springs, Colorado, United States, 80907
      • Teva Investigational Site 14368
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Teva Investigational Site 14244
    • Miami, Florida, United States, 33155
      • Teva Investigational Site 14325
    • West Palm Beach, Florida, United States, 33407
      • Teva Investigational Site 14250
    • West Palm Beach, Florida, United States, 33409
      • Teva Investigational Site 14255
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Teva Investigational Site 14243
    • Savannah, Georgia, United States, 31406
      • Teva Investigational Site 14258
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Teva Investigational Site 14263
    • Park Ridge, Illinois, United States, 60068
      • Teva Investigational Site 14283
  • Kansas
    • Wichita, Kansas, United States, 67206
      • Teva Investigational Site 14245
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Teva Investigational Site 14327
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Teva Investigational Site 14360
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Teva Investigational Site 14365
    • Silver Spring, Maryland, United States, 20910
      • Teva Investigational Site 14317
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Teva Investigational Site 14246
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Teva Investigational Site 14251
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Teva Investigational Site 14270
  • Mississippi
    • Ridgeland, Mississippi, United States, 39157
      • Teva Investigational Site 14376
  • Missouri
    • Bridgeton, Missouri, United States, 63044-2513
      • Teva Investigational Site 14256
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Teva Investigational Site 14371
  • New York
    • Amherst, New York, United States, 14226
      • Teva Investigational Site 14276
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Teva Investigational Site 14377
    • Raleigh, North Carolina, United States, 27607
      • Teva Investigational Site 14248
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Teva Investigational Site 14264
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Teva Investigational Site 14257
    • Oklahoma City, Oklahoma, United States, 73116
      • Teva Investigational Site 14275
    • Tulsa, Oklahoma, United States, 74136
      • Teva Investigational Site 14363
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4318
      • Teva Investigational Site 14364
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Teva Investigational Site 14374
  • Texas
    • Austin, Texas, United States, 78731
      • Teva Investigational Site 14252
    • Austin, Texas, United States, 78759
      • Teva Investigational Site 14273
    • Dallas, Texas, United States, 75235-7701
      • Teva Investigational Site 14367
    • Houston, Texas, United States, 77087
      • Teva Investigational Site 14312
    • Houston, Texas, United States, 77024
      • Teva Investigational Site 14274
    • San Antonio, Texas, United States, 78207
      • Teva Investigational Site 14366
    • San Antonio, Texas, United States, 78240
      • Teva Investigational Site 14241
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Teva Investigational Site 14375
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Teva Investigational Site 14323
  • Washington
    • Tacoma, Washington, United States, 98405
      • Teva Investigational Site 14277

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The participant has a clinical history of recurrent headache consistent with the diagnosis of migraine for at least 6 months before screening, consistent with ICHD-3 criteria (Headache Classification Committee of the IHS 2013), and a history of ≥15 headache days per month on average during the 3 months prior to screening (visit 1).
• The participant or parent/caregiver maintain a prospectively collected headache diary

NOTE: Additional criteria apply; please contact the investigator for more information.

Exclusion Criteria:

• The participant 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.
• The participant 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.
• 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 past or current history of cancer.
• The participant is pregnant or nursing.
• 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 has a current or past medical history of hemiplegic migraine.

NOTE: Additional criteria apply; please contact the investigator for more information.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Matching placebo
Experimental: Fremanezumab Dose A; Participants weighing < threshold will receive Dose A subcutaneously monthly for 3 months.	Drug: Fremanezumab; Dose A or Dose B subcutaneous
Experimental: Fremanezumab Dose B; Participants weighing ≥ threshold will receive Dose B subcutaneously monthly for 3 months.	Drug: Fremanezumab; Dose A or Dose B subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Monthly Average Number of Migraine Days During 12-Week Period After the First Dose of Study Drug	A migraine day was defined as a day with any of the following: A day (0:00 to 23:59) with at least 2 hours of headache with ≥2 migraine symptom(s) or day (0:00 to 23:59) demonstrating a headache treated with migraine medications (e.g., non-steroidal anti-inflammatory drugs [NSAIDs], paracetamol etc.), or a headache associated with aura. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in electronic diary (e-diary) for 12-week period) * 28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA).	Baseline (Day -28 to Day -1), up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.	Baseline and Month 3
Mean Change From Baseline in Quality of Life at Week 12, as Measured by Pediatric Quality of Life Inventory (PedsQL) Questionnaire	PedsQL 4.0 is a brief 23-item health-related quality of life (QoL) instrument that evaluates QoL in 4 areas of functioning: physical, emotional, social, and school functioning. For child and adolescent self-report (8 - 18 years) and parent report forms, respondents used a 5-point Likert scale to rate item severity (0=never a problem;1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem). For younger children (5 - 7 years), a simplified 3-point Likert scale, anchored with a happy and a sad face, was used (0=not at all a problem; 2=sometimes a problem; 4=a lot of a problem). PedsQL yields a total QoL score and 2 summary scores: Physical Health Summary Score and Psychosocial Health Summary Score. To obtain scores, items were reverse scored, transformed to a 0 through 100 scale (0=100, 1=75, 2=50, 3=25, 4=0), and averaged; total scores near 0 indicated lower QoL, while scores approaching 100 indicated higher QoL. LS mean was calculated using ANCOVA.	Baseline, Week 12
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline up to Month 3
Number of Participants With Shift From Baseline to Last Assessment in Electrocardiogram (ECG) Findings (Assessed by Investigator)	The number of participants with a shift from Baseline (Normal, Abnormal CS [Clinically Significant], or Abnormal NCS [Not Clinically Significant]) in any of the following ECG parameters is reported by treatment group: Heart rate, PR interval, QRS interval, RR interval, QT interval, QT interval corrected using the Bazett's formula (QTcB), and QT interval corrected using the Fridericia formula (QTcF). Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline to last assessment (up to Month 3)
Number of Participants With Shift From Baseline to Last Assessment in ECG Findings (Assessed by Cardiologist)	The number of participants with a shift from Baseline (Normal or Abnormal) in any of the following ECG parameters is reported by treatment group: Heart rate, PR interval, QRS interval, RR interval, QT interval, QTcB, and QTcF. Last assessment was defined as the last observed postbaseline interpretation. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline to last assessment (up to Month 3)
Mean Change From Baseline in Migraine-related Disability Score at Week 12, as Measured by the Pediatric Migraine Disability Assessment (PedMIDAS) Questionnaire	The PedMIDAS is a scale developed to assess headache-related disability which can be self-administered by the participant or administered by a caregiver. It has been validated in participants aged 4 to 18 years and includes 3 subscales: the impact of headache on school performance (range of scores 0-92), disability at home (range of scores 0-92), social/sport functioning (range of scores 0-92). The subscales are added to get the total score with a range 0 to 276. The total score was used for grading of disability, with 4 score categories of 0 to 10, 11 to 30, 31 to 50, and 51-276 interpreted as disability grades 1 (little or no disability), 2 (mild disability), 3 (moderate disability), and 4 (severe disability), respectively. Higher total scores indicated severe disability. LS mean was calculated using ANCOVA. The change from baseline score is reported with a range of -276 to 276 with higher scores indicating more severe disability.	Baseline, Week 12
Number of Participants Developing Anti-drug Antibodies (ADAs) Throughout the Study	Number of participants who developed ADAs were reported.	Baseline up to Month 3
Number of Participants With Any One or More Potentially Clinically Significant Vital Sign Abnormalities	Potentially clinically significant abnormal vital signs findings included any one of the following: Pulse rate ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm, or ≤50 bpm and decrease from baseline of ≥15 bpm; or ≤60 bpm and decrease from baseline of ≥15 bpm; and Respiratory rate <15 breaths/minute. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline up to Month 3
Number of Participants With Potentially Clinically Significant Abnormal Laboratory (Serum Chemistry, Hematology, Coagulation, and Urinalysis) Results	Serum chemistry tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≥2*upper limit of normal (ULN); and bilirubin ≥34.2 micromole/liter (umol/L). Hematology tests with potentially clinically significant abnormal findings included: hemoglobin ≤100 grams (g)/L, leukocytes ≤3*10^9 cells/L, and eosinophils/leukocytes ≥10%. Coagulation parameter test with potentially clinically significant abnormal findings included: prothrombin international normalized ratio (INR) >1.5. Urinalysis laboratory tests with potentially clinically significant abnormal findings included: urine protein ≥2 units (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline up to Month 3
Number of Participants With Abnormal Physical Examination Findings as Identified by the Investigator	A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat (HEENT); chest and lungs; cardiovascular; abdomen; musculoskeletal; skin; lymph nodes; neurological, and extremities/back. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	Baseline up to Month 3
Mean Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During 12-Week Period After the First Dose of Study Drug	A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the participant reported either of the following: A day with headache pain that lasted ≥2 hours with a peak severity of at least moderate severity or a day where the participant used acute headache medication (triptans, ergots, NSAIDs, or paracetamol) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. LS mean was calculated using ANCOVA.	Baseline (Day -28 to Day -1), up to Week 12
Number of Participants 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	A migraine day was defined as a calendar day where the participant reported either of the following: A calendar day (00:00 to 23:59) demonstrating at least 2 consecutive hours of a headache that was accompanied by ≥1 migraine symptom(s) or a calendar day (00:00 to 23:59) demonstrating a headache of any duration that was treated with acute headache medications (NSAIDs, paracetamol or triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. LS mean was calculated using ANCOVA.	Baseline (Day -28 to Day -1) up to Week 12
Mean Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During 12-Week Period After the First Dose of Study Drug	Participants recorded any headache medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken each day in their electronic headache diary device. Acute headache medication included triptans and ergot compounds, NSAIDs, or paracetamol. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12-week period/number of days with assessments recorded in e-diary for 12-week period) * 28. LS mean was calculated using ANCOVA.	Baseline (Day -28 to Day -1), up to Week 12

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 24, 2020
• Primary Completion (Actual): November 29, 2024
• Study Completion (Actual): November 29, 2024

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: July 6, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; fremanezumab
• Other Study ID Numbers: TV48125-CNS-30082; 2019-002053-33 (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