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

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

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

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: TEV-48125; Drug: TEV-48125 or placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 357
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Iruma, Japan
    • Saitama Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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.

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

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

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 group; Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).	Drug: Placebo; Placebo will be subcutaneously administered once monthly for 3 months.
Experimental: TEV-48125 (225/225/225 mg) group; TEV-48125 will be subcutaneously administered once monthly for 3 months (225/225/225 mg).	Drug: TEV-48125; TEV-48125 will be subcutaneously administered once monthly for 3 months.
Experimental: TEV-48125 (675 mg/placebo/placebo) group; TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/placebo/placebo).	Drug: TEV-48125 or placebo; TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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.	Baseline, 4 weeks

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2017
• Primary Completion (Actual): November 22, 2019
• Study Completion (Actual): November 22, 2019

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

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; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 406-102-00002; JapicCTI-173725 (Other Identifier: Japic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No