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

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04530110

Collaborator

(none)

550

Enrollment

Locations

Arm

85.7

Anticipated Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 60 months.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Fremanezumab	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

550 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 16, 2020

Anticipated Primary Completion Date :

Jun 20, 2027

Anticipated Study Completion Date :

Nov 7, 2027

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [Day 1 - Day 393]
including local injection site reaction/pain
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 [Day 1 - Day 253]
(systolic and diastolic blood pressure, pulse, temperature, and respiratory rate), height, and weight measurements
Incidence of abnormal physical examination findings [Day 1- Day 393]
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

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 [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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, 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 patient 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 patient 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 14358	Phoenix	Arizona	United States	85016
2	Teva Investigational Site 14253	Banning	California	United States	92220
3	Teva Investigational Site 14361	Sacramento	California	United States	95815
4	Teva Investigational Site 14368	Colorado Springs	Colorado	United States	80907
5	Teva Investigational Site 14244	Jacksonville	Florida	United States	32256
6	Teva Investigational Site 14325	Miami	Florida	United States	33155
7	Teva Investigational Site 14316	Miami	Florida	United States	33186
8	Teva Investigational Site 14250	West Palm Beach	Florida	United States	33407
9	Teva Investigational Site 14255	West Palm Beach	Florida	United States	33409
10	Teva Investigational Site 14243	Atlanta	Georgia	United States	30328
11	Teva Investigational Site 14258	Savannah	Georgia	United States	31406
12	Teva Investigational Site 14245	Wichita	Kansas	United States	67206
13	Teva Investigational Site 14365	Baltimore	Maryland	United States	21201
14	Teva Investigational Site 14246	Waltham	Massachusetts	United States	02451
15	Teva Investigational Site 14251	Ann Arbor	Michigan	United States	48104
16	Teva Investigational Site 14270	Minneapolis	Minnesota	United States	55402
17	Teva Investigational Site 14376	Ridgeland	Mississippi	United States	39157
18	Teva Investigational Site 14256	Bridgeton	Missouri	United States	63044-2513
19	Teva Investigational Site 14276	Amherst	New York	United States	14226
20	Teva Investigational Site 14377	Durham	North Carolina	United States	27705-4699
21	Teva Investigational Site 14248	Raleigh	North Carolina	United States	27607
22	Teva Investigational Site 14275	Oklahoma City	Oklahoma	United States	73116
23	Teva Investigational Site 14363	Tulsa	Oklahoma	United States	74136
24	Teva Investigational Site 14374	Bristol	Tennessee	United States	37620
25	Teva Investigational Site 14252	Austin	Texas	United States	78731
26	Teva Investigational Site 14273	Austin	Texas	United States	78759
27	Teva Investigational Site 14274	Bellaire	Texas	United States	77401
28	Teva Investigational Site 14367	Dallas	Texas	United States	75235-7701
29	Teva Investigational Site 14312	Houston	Texas	United States	77087
30	Teva Investigational Site 14241	San Antonio	Texas	United States	78240
31	Teva Investigational Site 14375	Salt Lake City	Utah	United States	84109
32	Teva Investigational Site 14323	Norfolk	Virginia	United States	23510
33	Teva Investigational Site 11179	Ottawa	Ontario	Canada	K2G 1W2
34	Teva Investigational Site 40053	Helsinki		Finland	00380
35	Teva Investigational Site 40049	Kuopio		Finland	70210
36	Teva Investigational Site 40054	Oulu		Finland	90100
37	Teva Investigational Site 40052	Tampere		Finland	33521
38	Teva Investigational Site 32728	Bad Homburg		Germany	61348
39	Teva Investigational Site 32729	Berlin		Germany	13353
40	Teva Investigational Site 32726	Leipzig		Germany	4103
41	Teva Investigational Site 80170	Be'er Ya'akov		Israel	70300
42	Teva Investigational Site 80166	Haifa		Israel	31048
43	Teva Investigational Site 80168	Holon		Israel	58100
44	Teva Investigational Site 80169	Jerusalem		Israel	9124001
45	Teva Investigational Site 80167	Ramat Gan		Israel	5265601
46	Teva Investigational Site 80164	Safed		Israel	13100
47	Teva Investigational Site 80165	Tel-Aviv		Israel	64239
48	Teva Investigational Site 30230	Firenze		Italy	50139
49	Teva Investigational Site 30239	Milano		Italy	20132
50	Teva Investigational Site 30226	Milano		Italy	20148
51	Teva Investigational Site 30228	Milan		Italy	20133
52	Teva Investigational Site 30227	Pavia		Italy	27100
53	Teva Investigational Site 30225	Rome		Italy	163
54	Teva Investigational Site 38135	Nijmegen		Netherlands	6532 SZ
55	Teva Investigational Site 38136	Rotterdam		Netherlands	3015 GD
56	Teva Investigational Site 53441	Gdansk		Poland	80-389
57	Teva Investigational Site 53437	Kielce		Poland	25-316
58	Teva Investigational Site 53443	Krakow		Poland	30-363
59	Teva Investigational Site 53452	Krakow		Poland	30-539
60	Teva Investigational Site 53440	Lublin		Poland	20-582
61	Teva Investigational Site 53439	Poznan		Poland	60-355
62	Teva Investigational Site 53451	Poznan		Poland	60-848
63	Teva Investigational Site 53442	Szczecin		Poland	70-111
64	Teva Investigational Site 31271	Barcelona		Spain	8035
65	Teva Investigational Site 31270	Valencia		Spain	46026
66	Teva Investigational Site 31265	Valladolid		Spain	47010

Sponsors and Collaborators

Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Teva Branded Pharmaceutical Products R&D, Inc.

ClinicalTrials.gov Identifier:

NCT04530110

Other Study ID Numbers:

TV48125-CNS-30084
2019-002056-16

First Posted:

Aug 28, 2020

Last Update Posted:

Aug 24, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.

episodic migraine

chronic migraine

Additional relevant MeSH terms:

Migraine Disorders

Study Results

No Results Posted as of Aug 24, 2022