Trial Outcomes & Findings for A Multicenter Assessment of LBR-101 in High Frequency Episodic Migraine (NCT NCT02025556)
NCT ID: NCT02025556
Last Updated: 2022-01-24
Results Overview
A migraine day was endorsed when at least 1 of the following situations occurred: 1) A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for migraine, or 2) a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only one migraine criterion is missing, or 3) the participant used acute migraine medication (triptans and ergot compounds) to treat a headache of any duration, or 4) any of the above days preceded or followed by a day with a headache of any duration. This calculation was defined as the change from baseline in the number of headache days during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe.
COMPLETED
PHASE2
297 participants
Baseline to week 12
2022-01-24
Participant Flow
A total of 297 participants with episodic migraine were enrolled in the study.
Participants were assigned to receive either subcutaneous administration of 675 mg of fremanezumab (LBR-101) for three months, subcutaneous administration of 225 mg of fremanezumab (LBR-101) for three months, or subcutaneous administration of placebo for three months.
Participant milestones
| Measure |
Placebo
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Overall Study
STARTED
|
104
|
96
|
97
|
|
Overall Study
Safety Analysis Set
|
104
|
96
|
96
|
|
Overall Study
Intent-to-treat (ITT) Set
|
104
|
95
|
96
|
|
Overall Study
COMPLETED
|
98
|
83
|
88
|
|
Overall Study
NOT COMPLETED
|
6
|
13
|
9
|
Reasons for withdrawal
| Measure |
Placebo
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
4
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
0
|
|
Overall Study
Protocol Violation
|
2
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
3
|
6
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
0
|
|
Overall Study
Reason not reported
|
0
|
0
|
1
|
Baseline Characteristics
A Multicenter Assessment of LBR-101 in High Frequency Episodic Migraine
Baseline characteristics by cohort
| Measure |
Placebo
n=104 Participants
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=96 Participants
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=97 Participants
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
Total
n=297 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
42.0 Years
STANDARD_DEVIATION 11.62 • n=5 Participants
|
40.8 Years
STANDARD_DEVIATION 12.43 • n=7 Participants
|
40.7 Years
STANDARD_DEVIATION 12.56 • n=5 Participants
|
41.2 Years
STANDARD_DEVIATION 12.17 • n=4 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
261 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
92 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
251 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
85 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
233 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Years of migraine
|
21.2 Years
STANDARD_DEVIATION 14.1 • n=5 Participants
|
18.9 Years
STANDARD_DEVIATION 12.92 • n=7 Participants
|
16.9 Years
STANDARD_DEVIATION 12.25 • n=5 Participants
|
19.0 Years
STANDARD_DEVIATION 13.21 • n=4 Participants
|
|
Preventive medication use
Yes
|
28 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
86 Participants
n=4 Participants
|
|
Preventive medication use
No
|
76 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
211 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to week 12Population: Intent-to-treat (ITT) population includes all randomized participants that received at least one dose and obtained at least one endpoint measurement.
A migraine day was endorsed when at least 1 of the following situations occurred: 1) A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for migraine, or 2) a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only one migraine criterion is missing, or 3) the participant used acute migraine medication (triptans and ergot compounds) to treat a headache of any duration, or 4) any of the above days preceded or followed by a day with a headache of any duration. This calculation was defined as the change from baseline in the number of headache days during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe.
Outcome measures
| Measure |
Placebo
n=104 Participants
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=95 Participants
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=96 Participants
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Mean Change From Baseline in the Monthly Migraine Days During the 28-day Post Treatment Period Ending With Week 12
|
-3.46 Days
Standard Error 0.53
|
-6.27 Days
Standard Error 0.55
|
-6.09 Days
Standard Error 0.53
|
PRIMARY outcome
Timeframe: Baseline to week 12Population: Safety analysis set included all randomized participants who received at least one dose of study drug.
An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Placebo
n=104 Participants
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=96 Participants
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=96 Participants
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Number of Participants With at Least One Adverse Event
|
58 Participants
|
44 Participants
|
57 Participants
|
PRIMARY outcome
Timeframe: Up to week 12Population: Per planned analysis participants analyzed included all randomized participants who received at least one dose of study drug and reported at least one adverse event.
Adverse events were rated based on the investigator's clinical judgment. Mild: awareness of a sign or symptom that was easily tolerated Moderate: sign or symptom intense enough to interfere with usual activity Severe: interfered significantly with ability to do work or usual activity
Outcome measures
| Measure |
Placebo
n=58 Participants
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=44 Participants
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=57 Participants
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs)
Mild
|
29 Participants
|
20 Participants
|
31 Participants
|
|
Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs)
Moderate
|
27 Participants
|
20 Participants
|
26 Participants
|
|
Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs)
Severe
|
1 Participants
|
4 Participants
|
0 Participants
|
|
Number of Participants Reporting Mild, Moderate, and Severe Adverse Events (AEs)
Unknown severity
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to week 12Population: Intent-to-treat (ITT) population includes all randomized participants who received at least one dose of study medication and obtained at least one endpoint measurement.
A headache day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache of any severity or the participant used acute migraine medication (triptans and ergot compounds) to treat a headache. This calculation was defined as the change from baseline in the number of headache days during the 28-day post treatment period ending at week 12. Headache severity was rated daily by the participant as either no pain, mild, moderate, or severe.
Outcome measures
| Measure |
Placebo
n=104 Participants
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=95 Participants
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=96 Participants
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Change From Baseline in Number of Days With Headache of Any Severity
|
-3.52 Days
Standard Error 0.53
|
-6.14 Days
Standard Error 0.56
|
-6.10 Days
Standard Error 0.54
|
Adverse Events
Placebo
Low Dose
High Dose
Serious adverse events
| Measure |
Placebo
n=104 participants at risk
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=96 participants at risk
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=96 participants at risk
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Antiphospholipid syndrome
|
0.00%
0/104 • Baseline to week 12
|
0.00%
0/96 • Baseline to week 12
|
1.0%
1/96 • Number of events 1 • Baseline to week 12
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/104 • Baseline to week 12
|
1.0%
1/96 • Number of events 1 • Baseline to week 12
|
0.00%
0/96 • Baseline to week 12
|
|
Nervous system disorders
Migraine
|
0.00%
0/104 • Baseline to week 12
|
1.0%
1/96 • Number of events 1 • Baseline to week 12
|
0.00%
0/96 • Baseline to week 12
|
|
Nervous system disorders
Tremor
|
0.00%
0/104 • Baseline to week 12
|
0.00%
0/96 • Baseline to week 12
|
1.0%
1/96 • Number of events 1 • Baseline to week 12
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/104 • Baseline to week 12
|
1.0%
1/96 • Number of events 1 • Baseline to week 12
|
0.00%
0/96 • Baseline to week 12
|
Other adverse events
| Measure |
Placebo
n=104 participants at risk
Participants received subcutaneous placebo injections at one visit per month for three months (Day
1/week 0, Day 29/week 4, and Day 57/week 8).
|
Low Dose
n=96 participants at risk
Participants received 225 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
High Dose
n=96 participants at risk
Participants received 675 mg fremanezumab subcutaneously on Day 1/week 0, Day 29/week 4, and on Day 57/week 8.
|
|---|---|---|---|
|
General disorders
Injection site pain
|
5.8%
6/104 • Number of events 10 • Baseline to week 12
|
9.4%
9/96 • Number of events 13 • Baseline to week 12
|
4.2%
4/96 • Number of events 4 • Baseline to week 12
|
|
Infections and infestations
Sinusitis
|
2.9%
3/104 • Number of events 3 • Baseline to week 12
|
0.00%
0/96 • Baseline to week 12
|
5.2%
5/96 • Number of events 5 • Baseline to week 12
|
|
Nervous system disorders
Dizziness
|
0.00%
0/104 • Baseline to week 12
|
1.0%
1/96 • Number of events 2 • Baseline to week 12
|
5.2%
5/96 • Number of events 6 • Baseline to week 12
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products R&D, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER