Clinical trial NCT04530110: A Study to Test if Fremanezumab is Effective in Preventing Migraine in Children and Adolescents
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Migraine
Keywords: episodic migraine
chronic migraine
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-28
Enrollment: 476
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Day 1 - Day 393
measure: Incidence of participants with clinically significant changes in laboratory values
timeFrame: Day 1 - Day 253
measure: Incidence of abnormal standard 12-lead electrocardiogram (ECG) findings
timeFrame: Day 1 - Day 253
measure: Incidence of abnormal vital signs
timeFrame: Day 1 - Day 253
measure: Incidence of abnormal physical examination findings
timeFrame: Day 1- Day 393
measure: Yes/No suicidality ideation
timeFrame: Day 1 - Day 393
Secondary outcomes:
measure: Mean change in the number of headache days of at least moderate severity
timeFrame: Day 1 - Day 253
measure: Mean change in the number of migraine days
timeFrame: Day 1 - Day 253
measure: Proportion of participants reaching at least 50% reduction in the number of migraine days
timeFrame: Day 1 - Day 253
measure: Proportion of participants reaching at least 50% reduction in the number of headache days of at least moderate severity
timeFrame: Day 1 - Day 253
measure: Mean change in the number of days of use of any acute headache medications
timeFrame: Day 1 - Day 253
measure: Mean change in the PedMIDAS questionnaire score
timeFrame: Day 1 - Day 393
measure: Proportion of participants developing antidrug antibodies (ADAs) throughout the study
timeFrame: Day 1 - Day 393
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Teva Investigational Site 14319
state: Colorado
city: Colorado Springs
country: United States
facility: Teva Investigational Site 14368
state: Colorado
city: Jacksonville
country: United States
facility: Teva Investigational Site 14244
state: Florida
city: Miami
country: United States
facility: Teva Investigational Site 14325
state: Florida
city: West Palm Beach
country: United States
facility: Teva Investigational Site 14250
state: Florida
city: West Palm Beach
country: United States
facility: Teva Investigational Site 14255
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 14243
state: Georgia
city: Savannah
country: United States
facility: Teva Investigational Site 14258
state: Georgia
city: Hoffman Estates
country: United States
facility: Teva Investigational Site 14263
state: Illinois
city: Wichita
country: United States
facility: Teva Investigational Site 14245
state: Kansas
city: Louisville
country: United States
facility: Teva Investigational Site 14327
state: Kentucky
city: Covington
country: United States
facility: Teva Investigational Site 14360
state: Louisiana
city: Baltimore
country: United States
facility: Teva Investigational Site 14365
state: Maryland
city: Waltham
country: United States
facility: Teva Investigational Site 14246
state: Massachusetts
city: Ann Arbor
country: United States
facility: Teva Investigational Site 14251
state: Michigan
city: Minneapolis
country: United States
facility: Teva Investigational Site 14270
state: Minnesota
city: Ridgeland
country: United States
facility: Teva Investigational Site 14376
state: Mississippi
city: Bridgeton
country: United States
facility: Teva Investigational Site 14256
state: Missouri
city: New Brunswick
country: United States
facility: Teva Investigational Site 14371
state: New Jersey
city: Amherst
country: United States
facility: Teva Investigational Site 14276
state: New York
city: Durham
country: United States
facility: Teva Investigational Site 14377
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 14248
state: North Carolina
city: Cincinnati
country: United States
facility: Teva Investigational Site 14264
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 14257
state: Oklahoma
city: Tulsa
country: United States
facility: Teva Investigational Site 14363
state: Oklahoma
city: Philadelphia
country: United States
facility: Teva Investigational Site 14364
state: Pennsylvania
city: Bristol
country: United States
facility: Teva Investigational Site 14374
state: Tennessee
city: Austin
country: United States
facility: Teva Investigational Site 14252
state: Texas
city: Austin
country: United States
facility: Teva Investigational Site 14273
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 14367
state: Texas
city: Salt Lake City
country: United States
facility: Teva Investigational Site 14375
state: Utah
city: Norfolk
country: United States
facility: Teva Investigational Site 14323
state: Virginia
city: Ottawa
country: Canada
facility: Teva Investigational Site 11182
state: Ontario
city: Ottawa
country: Canada
facility: Teva Investigational Site 11179
state: Ontario
city: Montreal
country: Canada
facility: Teva Investigational Site 11181
state: Quebec
city: Helsinki
country: Finland
facility: Teva Investigational Site 40053
city: Kuopio
country: Finland
facility: Teva Investigational Site 40049
city: Oulu
country: Finland
facility: Teva Investigational Site 40054
city: Tampere
country: Finland
facility: Teva Investigational Site 40052
city: Bad Homburg
country: Germany
facility: Teva Investigational Site 32728
city: Berlin
country: Germany
facility: Teva Investigational Site 32729
city: Leipzig
country: Germany
facility: Teva Investigational Site 32726
city: Be'er Ya'akov
country: Israel
facility: Teva Investigational Site 80170
city: Haifa
country: Israel
facility: Teva Investigational Site 80166
city: Holon
country: Israel
facility: Teva Investigational Site 80168
city: Jerusalem
country: Israel
facility: Teva Investigational Site 80169
city: Ramat Gan
country: Israel
facility: Teva Investigational Site 80167
city: Safed
country: Israel
facility: Teva Investigational Site 80164
city: Tel-Aviv
country: Israel
facility: Teva Investigational Site 80165
city: Firenze
country: Italy
facility: Teva Investigational Site 30230
city: Milano
country: Italy
facility: Teva Investigational Site 30239
city: Milano
country: Italy
facility: Teva Investigational Site 30228
city: Milano
country: Italy
facility: Teva Investigational Site 30226
city: Padua
country: Italy
facility: Teva Investigational Site 30238
city: Pavia
country: Italy
facility: Teva Investigational Site 30227
city: Rome
country: Italy
facility: Teva Investigational Site 30225
city: Doetinchem
country: Netherlands
facility: Teva Investigational Site 38138
city: Nijmegen
country: Netherlands
facility: Teva Investigational Site 38135
city: Rotterdam
country: Netherlands
facility: Teva Investigational Site 38136
city: Gdansk
country: Poland
facility: Teva Investigational Site 53441
city: Kielce
country: Poland
facility: Teva Investigational Site 53437
city: Krakow
country: Poland
facility: Teva Investigational Site 53443
city: Krakow
country: Poland
facility: Teva Investigational Site 53452
city: Lublin
country: Poland
facility: Teva Investigational Site 53440
city: Poznan
country: Poland
facility: Teva Investigational Site 53439
city: Poznan
country: Poland
facility: Teva Investigational Site 53451
city: Szczecin
country: Poland
facility: Teva Investigational Site 53442
city: Barcelona
country: Spain
facility: Teva Investigational Site 31271
city: Valencia
country: Spain
facility: Teva Investigational Site 31270
city: Valladolid
country: Spain
facility: Teva Investigational Site 31265
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: