MigrainePhase 2/3NCT03303092

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

A Phase 2/3 study testing TEV-48125 in people with Migraine, run by Otsuka Pharmaceutical Co., Ltd. at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

To evaluate the efficacy and safety of subcutaneous (SC) administration of TEV-48125 (monthly TEV-48125 225 mg and TEV-48125 675 mg once over a period of 3 months) compared with placebo for preventive treatment in Episodic Migraine patients Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Migraine
What is being tested?: TEV-48125
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 357 participants
Where: 1 siteJapan
Study dates: 19 Dec 2017to 22 Nov 2019
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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 Episodic 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.

Who cannot join

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
Hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease considered clinically significant in the judgment of the investigator

Trial locations and contacts

1 site in 1 country.

Japan1 site

Saitama Medical University Hospital
Iruma

Other trials in Japan

About this study

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Episodic Migraine

Conditions: Migraine
Being tested: TEV-48125, TEV-48125 or placebo, Placebo
Medical subject headings: Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TEV-48125Drug
TEV-48125 will be subcutaneously administered once monthly for 3 months.
TEV-48125 or placeboDrug
TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.
PlaceboDrug
Placebo will be subcutaneously administered once monthly for 3 months.

Study groups in NCT03303092
Study group	Role	What they receive
TEV-48125 (225/225/225 mg) group	Experimental	TEV-48125 will be subcutaneously administered once monthly for 3 months (225/225/225 mg). Receives: Drug: TEV-48125
TEV-48125 (675 mg/placebo/placebo) group	Experimental	TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/placebo/placebo). Receives: Drug: TEV-48125 or placebo
Placebo group	Placebo comparator	Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days 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, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period.
Subjects who reported 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 follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Measured: Baseline, 12 weeks

Secondary outcomes (4)

Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period.
Subjects who reported 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 follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Measured: 12 weeks
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
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 reported 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).
Measured: Baseline, 12 weeks
Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period.
Subjects who reported 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 follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Measured: Baseline, 12 weeks
Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP
Using the MIDAS questionnaire, subjects assessed the degree of headache-related disability based on lost days of activity in 3 domains (work, household work, and nonwork) over the last 3 months. The MIDAS questionnaire was a 5-item instrument. The total of the scores of the first 5 questions was used for grading the level of disability, with scores of 0 to 5, 6 to 10, 11 to 20, and ≥ 21 interpreted as disability grades I (little or no disability), II (mild disability), III (moderate disability), and IV (severe disability), respectively.
Measured: Baseline, 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Dec 201722 Nov 2019

First posted5 Oct 2017
Study start19 Dec 2017
Primary completion22 Nov 2019
Study completion22 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for MigraineStudies of the same condition, open and under way.
More trials run by Otsuka Pharmaceutical Co., Ltd.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 357 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03303092
Sponsor's protocol ID: 406-102-00002
Other IDs: JapicCTI-173725
Status last verified: Jul 2021
First submitted: 2 Oct 2017
Last updated: 29 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Tatsumoto M, Ishida M, Iba K, Kim BK, Ning X, Osawa C, Nakai M, Kurita Y. Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Headache. 2025 Mar;65(3):399-406. doi: 10.1111/head.14810. Epub 2024 Sep 2.
PubMed 39221611
Takeshima T, Nakai M, Shibasaki Y, Ishida M, Kim BK, Ning X, Koga N. 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. J Headache Pain. 2022 Feb 9;23(1):24. doi: 10.1186/s10194-022-01393-0.
PubMed 35139816

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of the Glymphatic System in Migraine
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Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
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App-Based Migraine Treatment: The Health enSuite Study
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A Prospective Study of Rimegepant for Short-term Preventive Treatment of Night-shift-related Migraine in Healthcare Professionals
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Marine Lipids Ease Painful TMD
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All Migraine trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial Evaluating the Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Episodic Migraine
ClinicalTrials.gov ID: NCT03303092
Acronym / sponsor ID: 406-102-00002
Conditions: Migraine
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 357 participants (actual)
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: 19 Dec 2017 (actual)
Primary completion: 22 Nov 2019 (actual)
Study completion: 22 Nov 2019 (actual)
First posted: 5 Oct 2017 (actual)
Results: Posted 8 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
TEV-48125 (225/225/225 mg) group	Experimental	Drug: TEV-48125TEV-48125 will be subcutaneously administered once monthly for 3 months (225/225/225 mg).
TEV-48125 (675 mg/placebo/placebo) group	Experimental	Drug: TEV-48125 or placeboTEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/placebo/placebo).
Placebo group	Placebo comparator	Drug: PlaceboPlacebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 Episodic 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.

Key exclusion criteria (2 listed)

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
Hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease considered clinically significant in the judgment of the investigator

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TEV-48125TEV-48125 will be subcutaneously administered once monthly for 3 months.	Drug	TEV-48125 (225/225/225 mg) group
TEV-48125 or placeboTEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.	Drug	TEV-48125 (675 mg/placebo/placebo) group
PlaceboPlacebo will be subcutaneously administered once monthly for 3 months.	Drug	Placebo group

Primary outcome

Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)
Time frame: Baseline, 12 weeks
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported 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 follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

4 secondary outcomes

Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP
Time frame: 12 weeks
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
Time frame: Baseline, 12 weeks
Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications
Time frame: Baseline, 12 weeks
Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP
Time frame: Baseline, 4 weeks

Results and safety

Results posted to the registry on 8 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TEV-48125 (225/225/225 mg) Group	121	118
TEV-48125 (675 mg/Placebo/Placebo) Group	119	113
Placebo Group	117	112

Primary outcome: Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)

Time frame: Baseline, 12 weeks. Mean (Standard Error). Unit: days/month

Measure	TEV-48125 (225/225/225 mg) Group n = 121	TEV-48125 (675 mg/Placebo/Placebo) Group n = 117	Placebo Group n = 116
Value	-4.00 (0.37)	-4.02 (0.38)	-1.02 (0.38)

Population analysed: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of migraine days.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Double-blind treatment period (12 weeks). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TEV-48125 (225/225/225 mg) Group	0 of 121 (0%)	69 of 121 (57%)	0 of 121
TEV-48125 (675 mg/Placebo/Placebo) Group	0 of 118 (0%)	74 of 118 (62.7%)	0 of 118
Placebo Group	0 of 117 (0%)	77 of 117 (65.8%)	0 of 117

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39221611Tatsumoto M, Ishida M, Iba K, Kim BK, Ning X, Osawa C, Nakai M, Kurita Y. Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Headache. 2025 Mar;65(3):399-406. doi: 10.1111/head.14810. Epub 2024 Sep 2.
Derived from this study: PubMed 35139816Takeshima T, Nakai M, Shibasaki Y, Ishida M, Kim BK, Ning X, Koga N. 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. J Headache Pain. 2022 Feb 9;23(1):24. doi: 10.1186/s10194-022-01393-0.
Individual participant dataSharing planned: Undecided

Related trials for Migraine

RecruitingObservational study
Study of the Glymphatic System in Migraine
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Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
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App-Based Migraine Treatment: The Health enSuite Study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Takehisa Matsumaru study director

Otsuka Pharmaceutical Co., Ltd.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing TEV-48125 in people with Migraine, run by Otsuka Pharmaceutical Co., Ltd. at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP) (time frame: Baseline, 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03303092, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2021.