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

• ClinicalTrials.gov Identifier: NCT03303079
• Recruitment Status: Completed
• First Posted: October 5, 2017
• Results First Posted: June 15, 2021
• Last Update Posted: June 15, 2021
• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Otsuka Pharmaceutical Co., Ltd.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Migraine	Drug: TEV-48125; Drug: TEV-48125 or placebo; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 571 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Chronic Migraine
• Actual Study Start Date: December 19, 2017
• Actual Primary Completion Date: November 30, 2019
• Actual Study Completion Date: November 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: TEV-48125 (675/225/225 mg) group; TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 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.
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.

Outcome Measures

Primary Outcome Measures :

1. 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) [ Time Frame: 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 Outcome Measures :

1. Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP [ Time Frame: 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.

2. 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 [ Time Frame: 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.

3. 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 ]
   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).
4. 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 [ Time Frame: 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."

5. 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 [ Time Frame: 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).

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Japan

Saitama Medical University Hospital

Iruma, Japan

Sponsors and Collaborators

Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Takehisa Matsumaru; Otsuka Pharmaceutical Co., Ltd.

  Study Documents (Full-Text)

Documents provided by Otsuka Pharmaceutical Co., Ltd.:

Study Protocol  [PDF] July 8, 2019

Statistical Analysis Plan  [PDF] December 12, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03303079
• Other Study ID Numbers: 406-102-00001; JapicCTI-173723 ( Other Identifier: Japic )
• First Posted: October 5, 2017
• Results First Posted: June 15, 2021
• Last Update Posted: June 15, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs