Chronic Migraine
Conditions
Keywords
Headache, Migraine, Chronic Migraine
Brief summary
The purpose of the study is to determine whether monthly subcutaneous administration of LBR-101 (fremanezumab) is safe and provides migraine prevention in patients with chronic migraine.
Detailed description
Two distinct doses of subcutaneous LBR-101 (fremanezumab) administered monthly will be compared to placebo for safety and efficacy. The mean change from baseline in the number of cumulative headache hours measured at the 28-day period ending with week 12.
Interventions
Subcutaneously Administered LBR-101 Monthly x 3
DRUGLBR-101 Low Dose
Subcutaneously Administered LBR-101 Monthly x 3
DRUGPlacebo
Subcutaneously Administered Placebo (Vehicle) Monthly x 3
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males or females aged 18 to 65 years of age. * A signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study including any known and potential risks and available alternative treatments. * Chronic migraine meeting the diagnostic criteria listed in the International Classification of Headache Disorders (ICHD-III beta version, 2013) * Body Mass Index (BMI) of 17.5 to 37.5 kg/m2, and a total body weight between 50 kg and 120 kg inclusive. * Demonstrated compliance with the electronic headache diary during the run-in period headache data on a minimum of 22/28 days (80% diary compliance)
Exclusion criteria
* Onset of chronic migraine after the age of 50 years. * Subject has received onabotulinum toxin A for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 6 months prior to study entry. * Subject is using medications containing opioids (including codeine) or barbiturates (including Fiorinal®, Fioricet®, or any other combination containing butalbital) on more than 4 days per month for the treatment of migraine or for any other reason. * Failed \> 2 medication categories or \> 3 preventive medications (within two medication categories) due to lack of efficacy for prophylactic treatment of episodic or chronic migraine after an adequate therapeutic trial * Treatment with an investigational drug or device within 30 days of study entry or any prior exposure to a monoclonal antibody targeting the CGRP pathway.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline to week 12 | 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. |
| Number of Participants With at Least One Adverse Event | Baseline to week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline to week 12 | 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. |
Countries
United States
Participant flow
Recruitment details
A total of 264 participants with chronic migraine were enrolled in the study.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 89 |
| 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). | 88 |
| 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). | 87 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 3 |
| Overall Study | Lack of Efficacy | 2 | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 3 | 0 |
| Overall Study | Protocol Violation | 2 | 3 | 1 |
| Overall Study | Reason not specified | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 5 |
Baseline characteristics
| Characteristic | Placebo | LBR-101 Low Dose | LBR-101 High Dose | Total |
|---|---|---|---|---|
| Age, Continuous | 40.7 Years STANDARD_DEVIATION 11.46 | 40.0 Years STANDARD_DEVIATION 11.56 | 41.5 Years STANDARD_DEVIATION 12.89 | 40.8 Years STANDARD_DEVIATION 11.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 14 Participants | 10 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 74 Participants | 77 Participants | 229 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Preventive Medication Use No | 51 Participants | 53 Participants | 54 Participants | 158 Participants |
| Preventive Medication Use Yes | 38 Participants | 35 Participants | 33 Participants | 106 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 12 Participants | 9 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) White | 76 Participants | 70 Participants | 73 Participants | 219 Participants |
| Sex: Female, Male Female | 76 Participants | 76 Participants | 75 Participants | 227 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 12 Participants | 37 Participants |
| Years of migraine | 20.4 Years STANDARD_DEVIATION 13.14 | 15.8 Years STANDARD_DEVIATION 11.22 | 18.8 Years STANDARD_DEVIATION 12.2 | 18.3 Years STANDARD_DEVIATION 12.32 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 0 / 88 | 0 / 86 |
| other Total, other adverse events | 3 / 89 | 6 / 88 | 8 / 86 |
| serious Total, serious adverse events | 1 / 89 | 1 / 88 | 2 / 86 |
Outcome results
Primary
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
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.
Time frame: Baseline to week 12
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| LBR-101 Low Dose | 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 | -59.84 Number of monthly headache hours | Standard Error 8.62 |
| LBR-101 High Dose | 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 | -67.51 Number of monthly headache hours | Standard Error 8.61 |
p-value: 0.038695% CI: [-44.28, -1.21]Mixed Models Analysis
p-value: 0.005795% CI: [-51.88, -8.95]Mixed Models Analysis
Primary
Number of Participants With at Least One Adverse Event
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.
Time frame: Baseline to week 12
Population: Safety analysis set included all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With at Least One Adverse Event | 36 Participants |
| LBR-101 Low Dose | Number of Participants With at Least One Adverse Event | 47 Participants |
| LBR-101 High Dose | Number of Participants With at Least One Adverse Event | 41 Participants |
Secondary
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
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.
Time frame: Baseline to week 12
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| LBR-101 Low Dose | 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 | -6.04 Number of headache days | Standard Error 0.687 |
| LBR-101 High Dose | 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 | -6.16 Number of headache days | Standard Error 0.686 |