Trial Outcomes & Findings for Assessment of LBR-101 In Chronic Migraine (NCT NCT02021773)
NCT ID: NCT02021773
Last Updated: 2021-12-09
Results Overview
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 hours with headache of any severity 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
264 participants
Baseline to week 12
2021-12-09
Participant Flow
A total of 264 participants with chronic migraine were enrolled in the study.
Participants were assigned to receive either monthly subcutaneous administration of 900 mg of LBR-101 (fremanezumab), subcutaneous loading dose of 675 mg of LBR-101 (fremanezumab) followed by monthly subcutaneous doses of 225 mg of LBR-101 (fremanezumab), or monthly subcutaneous doses of placebo.
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).
|
LBR-101 Low Dose
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
Overall Study
STARTED
|
89
|
88
|
87
|
|
Overall Study
Safety Analysis Set
|
89
|
88
|
86
|
|
Overall Study
Intent-to-treat (ITT)
|
89
|
87
|
85
|
|
Overall Study
COMPLETED
|
77
|
72
|
76
|
|
Overall Study
NOT COMPLETED
|
12
|
16
|
11
|
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).
|
LBR-101 Low Dose
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
4
|
3
|
|
Overall Study
Lack of Efficacy
|
2
|
2
|
2
|
|
Overall Study
Protocol Violation
|
2
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
4
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
0
|
|
Overall Study
Reason not specified
|
3
|
0
|
0
|
Baseline Characteristics
Assessment of LBR-101 In Chronic Migraine
Baseline characteristics by cohort
| Measure |
Placebo
n=89 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).
|
LBR-101 Low Dose
n=88 Participants
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
n=87 Participants
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
Total
n=264 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
78 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
229 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 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
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
76 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
219 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
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Years of migraine
|
20.4 Years
STANDARD_DEVIATION 13.14 • n=5 Participants
|
15.8 Years
STANDARD_DEVIATION 11.22 • n=7 Participants
|
18.8 Years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
18.3 Years
STANDARD_DEVIATION 12.32 • n=4 Participants
|
|
Preventive Medication Use
Yes
|
38 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
106 Participants
n=4 Participants
|
|
Preventive Medication Use
No
|
51 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
158 Participants
n=4 Participants
|
|
Age, Continuous
|
40.7 Years
STANDARD_DEVIATION 11.46 • n=5 Participants
|
40.0 Years
STANDARD_DEVIATION 11.56 • n=7 Participants
|
41.5 Years
STANDARD_DEVIATION 12.89 • n=5 Participants
|
40.8 Years
STANDARD_DEVIATION 11.95 • n=4 Participants
|
|
Sex: Female, Male
Female
|
76 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
227 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to week 12Population: Intent-to-treat (ITT) population includes all randomized participants who received at least one dose of study drug 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 hours with headache of any severity 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=89 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).
|
LBR-101 Low Dose
n=87 Participants
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
n=85 Participants
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
Mean Change From Baseline in the Number of Monthly Cumulative Headache Hours of Any Severity on Headache Days Relative to the 28-day Post-treatment Period Ending With Week 12
|
-37.10 Number of monthly headache hours
Standard Error 8.42
|
-59.84 Number of monthly headache hours
Standard Error 8.62
|
-67.51 Number of monthly headache hours
Standard Error 8.61
|
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=89 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).
|
LBR-101 Low Dose
n=88 Participants
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
n=86 Participants
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
Number of Participants With at Least One Adverse Event
|
36 Participants
|
47 Participants
|
41 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 of at least moderate severity 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=89 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).
|
LBR-101 Low Dose
n=87 Participants
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
n=85 Participants
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
Mean Change From Baseline in the Number of Headache Days of at Least Moderate Severity Relative to the 28-day Post-treatment Period Ending With Week 12
|
-4.20 Number of headache days
Standard Error 0.67
|
-6.04 Number of headache days
Standard Error 0.687
|
-6.16 Number of headache days
Standard Error 0.686
|
Adverse Events
Placebo
LBR-101 Low Dose
LBR-101 High Dose
Serious adverse events
| Measure |
Placebo
n=89 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).
|
LBR-101 Low Dose
n=88 participants at risk
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
n=86 participants at risk
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
0.00%
0/89 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/88 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
1.2%
1/86 • Number of events 1 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/89 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
1.1%
1/88 • Number of events 1 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/86 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Psychiatric disorders
Depression
|
0.00%
0/89 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/88 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
1.2%
1/86 • Number of events 1 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/89 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/88 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
1.2%
1/86 • Number of events 1 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.1%
1/89 • Number of events 1 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/88 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
0.00%
0/86 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
Other adverse events
| Measure |
Placebo
n=89 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).
|
LBR-101 Low Dose
n=88 participants at risk
Participants received one subcutaneous loading dose of 675 mg LBR-101 (fremanezumab) on Day 1/week 0 followed by one subcutaneous dose of 225 mg LBR-101 (fremanezumab) once per month for two months (Day 29/week 4 and Day 57/week 8).
|
LBR-101 High Dose
n=86 participants at risk
Participants received one subcutaneous dose of 900 mg LBR-101 (fremanezumab) once per month for three months (Day 1/week 0, Day 29/week 4, and Day 57/week 8).
|
|---|---|---|---|
|
General disorders
Injection site pain
|
3.4%
3/89 • Number of events 5 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
6.8%
6/88 • Number of events 8 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
9.3%
8/86 • Number of events 10 • Up to 12 weeks after first dose of treatment drug.
Safety analysis set included all participants that received at least one dose of study treatment.
|
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