Trial Outcomes & Findings for Long-term Safety and Tolerability of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Migraine (NCT NCT03303105)

NCT ID: NCT03303105

Last Updated: 2023-02-17

Results Overview

* 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

50 participants

Primary outcome timeframe

Baseline (Day 0) up to follow-up visit (Day 562)

Results posted on

2023-02-17

Participant Flow

Participant milestones

Participant milestones
Measure
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 chronic migraine).
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).
Overall Study
STARTED
25
25
Overall Study
COMPLETED
23
21
Overall Study
NOT COMPLETED
2
4

Reasons for withdrawal

Reasons for withdrawal
Measure
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 chronic migraine).
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).
Overall Study
Adverse Event
0
2
Overall Study
Lack of Efficacy
1
0
Overall Study
Protocol Violation
1
0
Overall Study
Withdrawal by Subject
0
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
TEV-48125 (225 mg/1 Month) Group
n=25 Participants
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 chronic migraine).
TEV-48125 (675 mg/3 Month) Group
n=25 Participants
TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
Total
n=50 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
24 Participants
n=5 Participants
25 Participants
n=7 Participants
49 Participants
n=5 Participants
Age, Categorical
>=65 years
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Continuous
46.8 years
STANDARD_DEVIATION 7.9 • n=5 Participants
45.8 years
STANDARD_DEVIATION 7.0 • n=7 Participants
46.3 years
STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male
Female
23 Participants
n=5 Participants
19 Participants
n=7 Participants
42 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
6 Participants
n=7 Participants
8 Participants
n=5 Participants
Race/Ethnicity, Customized
Japanese
25 Participants
n=5 Participants
25 Participants
n=7 Participants
50 Participants
n=5 Participants
Region of Enrollment
Japan
25 Participants
n=5 Participants
25 Participants
n=7 Participants
50 Participants
n=5 Participants

PRIMARY outcome

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

Population: Safety Set (SS): Newly enrolled subjects who received the IMP at least once

* 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.

Outcome measures

Outcome measures
Measure
TEV-48125 (225 mg/1 Month) Group
n=25 Participants
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 chronic migraine).
TEV-48125 (675 mg/3 Month) Group
n=25 Participants
TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)
92.0 percentage of participants
88.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Full Analysis set (FAS): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available

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.

Outcome measures

Outcome measures
Measure
TEV-48125 (225 mg/1 Month) Group
n=23 Participants
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 chronic migraine).
TEV-48125 (675 mg/3 Month) Group
n=22 Participants
TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days
-5.9 days/month
Standard Deviation 4.3
-1.6 days/month
Standard Deviation 5.7

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Full Analysis set (FAS): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available

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.

Outcome measures

Outcome measures
Measure
TEV-48125 (225 mg/1 Month) Group
n=23 Participants
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 chronic migraine).
TEV-48125 (675 mg/3 Month) Group
n=22 Participants
TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity
-4.3 days/month
Standard Deviation 4.1
-2.1 days/month
Standard Deviation 4.1

Adverse Events

TEV-48125 (225 mg/1 Month) Group

Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths

TEV-48125 (675 mg/3 Month) Group

Serious events: 2 serious events
Other events: 16 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
TEV-48125 (225 mg/1 Month) Group
n=25 participants at risk
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 chronic migraine).
TEV-48125 (675 mg/3 Month) Group
n=25 participants at risk
TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
Eye disorders
Rhegmatogenous retinal detachment
0.00%
0/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Nervous system disorders
Subarachnoid haemorrhage
0.00%
0/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once

Other adverse events

Other adverse events
Measure
TEV-48125 (225 mg/1 Month) Group
n=25 participants at risk
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 chronic migraine).
TEV-48125 (675 mg/3 Month) Group
n=25 participants at risk
TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months).
General disorders
Injection site pruritus
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
General disorders
Injection site induration
12.0%
3/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
General disorders
Injection site erythema
28.0%
7/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
20.0%
5/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
General disorders
Injection site pain
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
12.0%
3/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Infections and infestations
Influenza
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Infections and infestations
Gastroenteritis
12.0%
3/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Infections and infestations
Oral herpes
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Infections and infestations
Nasopharyngitis
72.0%
18/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
56.0%
14/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders
Back pain
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders
Cough
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
Reproductive system and breast disorders
Dysmenorrhoea
8.0%
2/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once
4.0%
1/25 • Baseline (Day 0) up to follow-up visit (Day 562)
Safety Set (SS): Newly enrolled subjects who received the IMP at least once

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place