Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Chronic Migraine

Conditions

Migraine

Brief summary

To evaluate the efficacy and safety of subcutaneous (SC) administration of TEV-48125 \[monthly TEV-48125 225 mg (loading dose only: 675 mg) and TEV-48125 675 mg once over a period of 3 months\] compared with placebo for preventive treatment in Chronic Migraine patients

Saigoh K, Takeshima T, Nakai M, Shibasaki Y, Ishida M, Ning X, Barash S, Isogai Y, Koga N.

2023-04-201 citations

10.2147/jpr.s393854

Early onset of efficacy with fremanezumab in patients with episodic and chronic migraine: subanalysis of two phase 2b/3 trials in Japanese and Korean patients

Takao Takeshima, Masami Nakai, Yoshiyuki Shibasaki, Miki Ishida, Byung‐Kun Kim et al. (7 authors)

The Journal of Headache and Pain2022-02-0913 citations

10.1186/s10194-022-01393-0

Interventions

DRUGTEV-48125

TEV-48125 will be subcutaneously administered once monthly for 3 months.

DRUGTEV-48125 or placebo

TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.

DRUGPlacebo

Placebo will be subcutaneously administered once monthly for 3 months.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

No

Inclusion criteria

* Patient has a history of migraine (according to The International Classification of Headache Disorders, third edition \[beta version\] criteria) or clinical judgment suggests a migraine diagnosis * Patient fulfills the criteria for Chronic migraine in baseline information collected during the 28 day screening period * Not using preventive migraine medications for migraine or other medical conditions or using no more than 1 preventive migraine medication for migraine or other medical conditions if the dose and regimen have been stable for at least 2 months prior to giving informed consent. * Patient demonstrates compliance with the electronic headache diary during the screening period by entry of headache data on a minimum of 24 of 28 days and the entered data is judged appropriate by the investigator.

Exclusion criteria

* Patients who have previously failed (lack of efficacy) 2 or more of the clusters of the medications for treatment of migraine after use for at least 3 months at accepted migraine therapeutic doses * Patient suffers from unremitting headaches, defined as having headaches for more than 80% of the time that he/she is awake, and less than 4 days without headache per month. Daily headache is acceptable if the patient has headaches 80% or less of the time they are awake on most days. * Hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease considered clinically significant in the judgment of the investigator

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)	Baseline, 12 weeks	Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP	Baseline, 12 weeks	Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP	12 weeks	Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP	Baseline, 12 weeks	Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).
Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP in Subjects Not Receiving Concomitant Preventive Migraine Medications	Baseline, 12 weeks	Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Mean Change From Baseline in Disability Score, as Measured by 6-Item Headache Impact Test (HIT-6) at 4 Weeks After the Final (Third) Dose of IMP	Baseline, 4 weeks	Subjects assessed the impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress, using the HIT-6. The HIT-6 total score will be obtained from summation of the 6 question points.Each question is answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always).

Countries

Japan

Participant flow

Participants by arm

Arm	Count
TEV-48125 (675/225/225 mg) Group TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	189
TEV-48125 (675 mg/Placebo/Placebo) Group TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	191
Placebo Group Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).	191
Total	571

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	0	1	3
Overall Study	Other than specified	0	2	0
Overall Study	Protocol Violation	5	4	7
Overall Study	Withdrawal by Subject	2	4	2

Baseline characteristics

Characteristic	TEV-48125 (675/225/225 mg) Group	TEV-48125 (675 mg/Placebo/Placebo) Group	Placebo Group	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	7 Participants	1 Participants	10 Participants
Age, Categorical Between 18 and 65 years	187 Participants	184 Participants	190 Participants	561 Participants
Age, Continuous	42.7 years STANDARD_DEVIATION 10.2	43.5 years STANDARD_DEVIATION 10.2	42.1 years STANDARD_DEVIATION 10.2	42.8 years STANDARD_DEVIATION 10.2
Race/Ethnicity, Customized Asian	189 Participants	191 Participants	191 Participants	571 Participants
Region of Enrollment Japan	159 participants	159 participants	161 participants	479 participants
Region of Enrollment South Korea	30 participants	32 participants	30 participants	92 participants
Sex: Female, Male Female	163 Participants	165 Participants	163 Participants	491 Participants
Sex: Female, Male Male	26 Participants	26 Participants	28 Participants	80 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 188	0 / 190	0 / 191
other Total, other adverse events	115 / 188	116 / 190	117 / 191
serious Total, serious adverse events	3 / 188	1 / 190	1 / 191

Outcome results

Primary

Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

Time frame: Baseline, 12 weeks