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CompletedNCT03303105Updated Feb 17, 2023Results posted

Long-term Safety and Tolerability of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Migraine

A Phase 3 interventional study of TEV-48125 and TEV-48125 in Migraine, sponsored by Otsuka Pharmaceutical Co., Ltd.. Completed at 1 site in Japan. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-02-17.

Sponsored by Otsuka Pharmaceutical Co., Ltd. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

To evaluate the long-term safety and tolerability of subcutaneous (SC) administration of TEV-48125 (at 225 mg once monthly [except for a loading dose of 675 mg for CM patients] or at 675 mg every 3 months) for the preventive treatment of Chronic Migraine and Episodic Migraine patients

02

Conditions studied

  • Migraine

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03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts 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 or 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 2 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

Exclusion Criteria:

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

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
50 participants (actual)

Study arms

  • Experimental
    TEV-48125 (225 mg/1 month) group

    TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly \[except for a loading dose of 675 mg in subjects with CM\]).

    Drug: TEV-48125

  • Experimental
    TEV-48125 (675 mg/3 month) group

    TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).

    Drug: TEV-48125

Interventions

  • DrugTEV-48125

    TEV-48125 will be administered subcutaneously once every 4 weeks.

  • DrugTEV-48125

    TEV-48125 will be administered subcutaneously once every 12 weeks.

05

What researchers measure

Primary outcomes

  1. Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)

    * TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term. * Specific AE terms are provided in the Adverse Event section.

    Time frame: Baseline (Day 0) up to follow-up visit (Day 562)

Secondary outcomes

  1. Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days

    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, Month 12

  2. Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity

    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, Month 12

06

Results

Posted Jul 16, 2021

Participant flow

Participant flow — Overall Study
MilestoneTEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) Group
Started2525
Completed2321
Not completed24
Withdrew: Adverse event02
Withdrew: Lack of efficacy10
Withdrew: Protocol violation10
Withdrew: Withdrawal by subject02

Outcome measures

PrimaryPercentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)

* TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term. * Specific AE terms are provided in the Adverse Event section.

Time frame:
Baseline (Day 0) up to follow-up visit (Day 562)
Reported as:
Number · percentage of participants
Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)
percentage of participantsTEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) Group
Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)92.088.0
SecondaryMean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days

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, Month 12
Reported as:
Mean · days/month
Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days
days/monthTEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) Group
Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days-5.9 ± 4.3-1.6 ± 5.7
SecondaryMean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity

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, Month 12
Reported as:
Mean · days/month
Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity
days/monthTEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) Group
Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity-4.3 ± 4.1-2.1 ± 4.1

Adverse events

Collected over Baseline (Day 0) up to follow-up visit (Day 562). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TEV-48125 (225 mg/1 Month) Group0/25 (0%)0/25 (0%)20/25 (80%)
TEV-48125 (675 mg/3 Month) Group0/25 (0%)2/25 (8%)16/25 (64%)
Most frequent serious events
Most frequent serious events
EventTEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) Group
Rhegmatogenous retinal detachmentEye disorders0/251/25
Subarachnoid haemorrhageNervous system disorders0/251/25
Most frequent other events
Showing 10 of 11
Most frequent other events
EventTEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) Group
NasopharyngitisInfections and infestations18/2514/25
Injection site erythemaGeneral disorders7/255/25
Injection site indurationGeneral disorders3/252/25
Injection site painGeneral disorders1/253/25
GastroenteritisInfections and infestations3/251/25
Injection site pruritusGeneral disorders2/251/25
InfluenzaInfections and infestations1/252/25
Oral herpesInfections and infestations1/252/25
Back painMusculoskeletal and connective tissue disorders1/252/25
CoughRespiratory, thoracic and mediastinal disorders1/252/25

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)TEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) GroupTotal
<=18 years000
Between 18 and 65 years242549
>=65 years101
Age, Continuous
Age, Continuous(years)TEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) GroupTotal
Mean46.8 ± 7.945.8 ± 7.046.3 ± 7.4
Sex: Female, Male
Sex: Female, Male(Participants)TEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) GroupTotal
Female231942
Male268
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)TEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) GroupTotal
Japanese252550
Region of Enrollment
Region of Enrollment(Participants)TEV-48125 (225 mg/1 Month) GroupTEV-48125 (675 mg/3 Month) GroupTotal
Japan252550
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Study locations

1 site
  • Saitama Medical University Hospital
    Iruma, Japan
08

References and documents

Publications

  • Sakai F, Suzuki N, Ning X, Ishida M, Usuki C, Iba K, Isogai Y, Koga N. Long-Term Safety and Tolerability of Fremanezumab for Migraine Preventive Treatment in Japanese Outpatients: A Multicenter, Randomized, Open-Label Study. Drug Saf. 2021 Dec;44(12):1355-1364. doi: 10.1007/s40264-021-01119-2. Epub 2021 Oct 23. PubMed 34687446 ↗

Study documents

  • Study protocol · Jul 8, 2019
  • Statistical analysis plan · Dec 11, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

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Registry details

Key details

Study ID
NCT03303105
Lead sponsor
Otsuka Pharmaceutical Co., Ltd.
Responsible party
Sponsor
First posted
Oct 5, 2017
Start date
Dec 7, 2017
Primary completion
Jun 16, 2020
Completion
Jun 16, 2020
Results posted
Jul 16, 2021
Last update
Feb 17, 2023

Study contacts

Takehisa Matsumaru
study director · Otsuka Pharmaceutical Co., Ltd.

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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