Trial Outcomes & Findings for A Study to Test if Fremanezumab Reduces Headache in Participants With Posttraumatic Headache (PTH) (NCT NCT03347188)
NCT ID: NCT03347188
Last Updated: 2022-12-13
Results Overview
A headache day was defined as a day when a participant reported a headache of at least moderate severity. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model with the duration of post traumatic headache history (less than 12 month since the brain injury or greater or equal to 12 month since the brain injury) and treatment as fixed effects and the baseline monthly average number of headache days of at least moderate severity as a covariate.
COMPLETED
PHASE2
87 participants
Baseline (Day -28 to Day -1), up to Week 12
2022-12-13
Participant Flow
Participant milestones
| Measure |
Fremanezumab
Participants received fremanezumab 675 milligrams (mg) administered as 3 subcutaneous (SC) injections (225 mg/1.5 milliliters \[mL\] each) at randomization (Week 0), Weeks 4, and 8 during the double-blind (DB) treatment period. Participants who completed the DB treatment period and continued into the open-label (OL) treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
Double-blind (DB) Period (12 Weeks)
STARTED
|
44
|
43
|
|
Double-blind (DB) Period (12 Weeks)
Received at Least 1 Dose of Study Drug
|
43
|
43
|
|
Double-blind (DB) Period (12 Weeks)
Full Analysis Set (FAS)
|
42
|
43
|
|
Double-blind (DB) Period (12 Weeks)
COMPLETED
|
29
|
26
|
|
Double-blind (DB) Period (12 Weeks)
NOT COMPLETED
|
15
|
17
|
|
Open-label (OL) Period (12 Weeks)
STARTED
|
35
|
35
|
|
Open-label (OL) Period (12 Weeks)
Entered in OL Period for Anti-drug Antibody (ADA) Only
|
26
|
28
|
|
Open-label (OL) Period (12 Weeks)
Received at Least 1 Dose of Study Drug
|
9
|
7
|
|
Open-label (OL) Period (12 Weeks)
COMPLETED
|
8
|
6
|
|
Open-label (OL) Period (12 Weeks)
NOT COMPLETED
|
27
|
29
|
Reasons for withdrawal
| Measure |
Fremanezumab
Participants received fremanezumab 675 milligrams (mg) administered as 3 subcutaneous (SC) injections (225 mg/1.5 milliliters \[mL\] each) at randomization (Week 0), Weeks 4, and 8 during the double-blind (DB) treatment period. Participants who completed the DB treatment period and continued into the open-label (OL) treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
Double-blind (DB) Period (12 Weeks)
Protocol Violation
|
2
|
2
|
|
Double-blind (DB) Period (12 Weeks)
Withdrawal by Subject
|
4
|
8
|
|
Double-blind (DB) Period (12 Weeks)
Lost to Follow-up
|
7
|
4
|
|
Double-blind (DB) Period (12 Weeks)
Adverse Event
|
1
|
1
|
|
Double-blind (DB) Period (12 Weeks)
Other than specified
|
1
|
2
|
|
Open-label (OL) Period (12 Weeks)
Entered for ADA assessment only, not treated
|
26
|
28
|
|
Open-label (OL) Period (12 Weeks)
Withdrawal by Subject
|
1
|
0
|
|
Open-label (OL) Period (12 Weeks)
Other than specified
|
0
|
1
|
Baseline Characteristics
'Number analyzed' signifies participants evaluable for this baseline measure.
Baseline characteristics by cohort
| Measure |
Fremanezumab
n=44 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.6 years
STANDARD_DEVIATION 13.01 • n=44 Participants
|
43.8 years
STANDARD_DEVIATION 14.48 • n=43 Participants
|
43.2 years
STANDARD_DEVIATION 13.68 • n=87 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=44 Participants
|
25 Participants
n=43 Participants
|
50 Participants
n=87 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=44 Participants
|
18 Participants
n=43 Participants
|
37 Participants
n=87 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=44 Participants
|
4 Participants
n=43 Participants
|
8 Participants
n=87 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=44 Participants
|
38 Participants
n=43 Participants
|
78 Participants
n=87 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=44 Participants
|
1 Participants
n=43 Participants
|
1 Participants
n=87 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
41 Participants
n=44 Participants
|
39 Participants
n=43 Participants
|
80 Participants
n=87 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
3 Participants
n=44 Participants
|
1 Participants
n=43 Participants
|
4 Participants
n=87 Participants
|
|
Race/Ethnicity, Customized
Race · Native Hawaiian or other Pacific Islander
|
0 Participants
n=44 Participants
|
1 Participants
n=43 Participants
|
1 Participants
n=87 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
0 Participants
n=44 Participants
|
2 Participants
n=43 Participants
|
2 Participants
n=87 Participants
|
|
Number of Headache Days of at Least Moderate Severity
|
18.7 days
STANDARD_DEVIATION 7.03 • n=43 Participants • 'Number analyzed' signifies participants evaluable for this baseline measure.
|
18.5 days
STANDARD_DEVIATION 6.12 • n=43 Participants • 'Number analyzed' signifies participants evaluable for this baseline measure.
|
18.6 days
STANDARD_DEVIATION 6.56 • n=86 Participants • 'Number analyzed' signifies participants evaluable for this baseline measure.
|
PRIMARY outcome
Timeframe: Baseline (Day -28 to Day -1), up to Week 12Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint.
A headache day was defined as a day when a participant reported a headache of at least moderate severity. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. Least square (LS) mean was calculated using analysis of covariance (ANCOVA) model with the duration of post traumatic headache history (less than 12 month since the brain injury or greater or equal to 12 month since the brain injury) and treatment as fixed effects and the baseline monthly average number of headache days of at least moderate severity as a covariate.
Outcome measures
| Measure |
Fremanezumab
n=42 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Mean Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Treatment Period After the First Dose of Fremanezumab
|
-3.6 days
Standard Error 0.99
|
-5.1 days
Standard Error 1.01
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day-1) up to Week 12Population: FAS included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint.
Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28.
Outcome measures
| Measure |
Fremanezumab
n=42 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of Any Severity During 12-Week Treatment With Fremanezumab
|
5 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day-1) up to Week 12Population: FAS included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint.
A headache day was defined as a day when a participant reported a headache of at least moderate severity. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28.
Outcome measures
| Measure |
Fremanezumab
n=42 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During 12-Week Treatment With Fremanezumab
|
9 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day-1) up to Months 1, 2, and 3Population: FAS included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.
A headache day was defined as a day when a participant reported a headache of at least moderate severity. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28.
Outcome measures
| Measure |
Fremanezumab
n=42 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)
Month 2
|
8 Participants
|
14 Participants
|
|
DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)
Month 1
|
8 Participants
|
11 Participants
|
|
DB Period: Number of Participants Reaching at Least 50% Reduction From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)
Month 3
|
14 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1), up to Months 1, 2, and 3Population: FAS included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints.
A headache day was defined as a day when a participant reported a headache of at least moderate severity. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. LS mean was calculated using ANCOVA model with the duration of post traumatic headache history (less than 12 month since the brain injury or greater or equal to 12 month since the brain injury) and treatment as fixed effects and the baseline monthly average number of headache days of at least moderate severity as a covariate. This approach was used in generating the LS mean values only and was not considered to be an additional statistical analysis, no additional statistical analyses are reported for this outcome measure.
Outcome measures
| Measure |
Fremanezumab
n=42 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Change From Baseline in the Number of Headache Days of At Least Moderate Severity During the First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)
Change at Month 1
|
-3.6 days
Standard Error 0.97
|
-4.0 days
Standard Error 0.99
|
|
DB Period: Change From Baseline in the Number of Headache Days of At Least Moderate Severity During the First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)
Change at Month 2
|
-3.7 days
Standard Error 1.06
|
-6.7 days
Standard Error 1.06
|
|
DB Period: Change From Baseline in the Number of Headache Days of At Least Moderate Severity During the First 4-Week (Month 1), 5- to 8-Week (Month 2), and 9- to 12-Week (Month 3)
Change at Month 3
|
-5.2 days
Standard Error 1.20
|
-7.2 days
Standard Error 1.21
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1), Week 12Population: FAS included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
HIT-6 is a tool used to measure the impact headaches have on a participant's normal daily life and ability to function. The HIT-6 consists of 6 items, including pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. Each item was answered on a 5-point Likert scale (6=never, 8=rarely, 10=sometimes, 11=very often, or 13=always), which were summed to produce a total score that ranged from 36 to 78, with larger scores reflecting greater impact of headache on the daily life of the participant.
Outcome measures
| Measure |
Fremanezumab
n=35 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=37 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Change From Baseline in Disability Score, as Measured by the 6-Item Headache Impact Test (HIT-6) Total Score at Week 12 After the First Dose of Fremanezumab
|
-6.9 units on a scale
Standard Error 4.54
|
-10.8 units on a scale
Standard Error 4.65
|
SECONDARY outcome
Timeframe: Weeks 4, 8, and 12Population: FAS included all randomized participants who received at least 1 dose of the study drug and had at least 1 post-baseline efficacy assessment on the primary endpoint.
The PGIC scale is a validated generic tool for the assessment of overall change in the severity of illness following treatment. Participants rated how they felt during assigned time points compared with how they felt before receiving study drug on a 7-point scale, where 1 = No change (or it got worse); 2 = Almost the same, hardly any change at all; 3 = A little better, but no noticeable change; 4 = Somewhat better, but the change has not made any real difference; 5 = Moderately better, and a slight but noticeable change; 6 = Better, and a definite improvement that has made a real and worthwhile difference; and 7 = A great deal better, and a considerable improvement that has made all the difference. Responders were those with a scale of 5 to 7 and non-responders were those with a scale of 1 to 4.
Outcome measures
| Measure |
Fremanezumab
n=42 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 4 · Responder
|
12 Participants
|
11 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 4 · Non-Responder
|
24 Participants
|
26 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 4 · Missing
|
6 Participants
|
6 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 8 · Responder
|
14 Participants
|
17 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 8 · Non-Responder
|
20 Participants
|
21 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 8 · Missing
|
8 Participants
|
5 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 12 · Responder
|
11 Participants
|
16 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 12 · Non-Responder
|
20 Participants
|
16 Participants
|
|
DB Period: Number of Participants (Responder and Non-Responder) With the Patient Global Impression of Change (PGIC) Scale at Weeks 4, 8, and 12 After the First Dose of Fremanezumab
Week 12 · Missing
|
11 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to -1) up to Week 12Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring at or after the first dose of the study drug. Serious AEs were defined as death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Fremanezumab
n=43 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
|
31 Participants
|
35 Participants
|
SECONDARY outcome
Timeframe: Week 12 up to Week 24Population: OL-ITT analysis set included only participants who received at least 1 dose of study drug during the open-label treatment period.
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as AEs occurring at or after the first dose of the study drug. Serious AEs were defined as death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Fremanezumab
n=9 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=7 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
OL Period: Number of Participants With TEAEs
|
8 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1) up to Week 12Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
Number of participants who did not complete the study due to any reason and due to AEs are reported.
Outcome measures
| Measure |
Fremanezumab
n=43 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants Who Did Not Complete the Study
Discontinued study due to any reason
|
15 Participants
|
17 Participants
|
|
DB Period: Number of Participants Who Did Not Complete the Study
Discontinued study due to AEs
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Week 12 up to Week 24Population: OL-ITT analysis set included only participants who received at least 1 dose of study drug during the open-label treatment period.
Number of participants who did not complete the study due to any reason and due to AEs are reported.
Outcome measures
| Measure |
Fremanezumab
n=9 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=7 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
OL Period: Number of Participants Who Did Not Complete the Study
Discontinued study due to any reason
|
1 Participants
|
1 Participants
|
|
OL Period: Number of Participants Who Did Not Complete the Study
Discontinued study due to AEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1) up to Week 12Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
Concomitant medications included: agents acting on renin-angiotensin system, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetics and antinauseants, antiepileptics, antifungals for dermatologiocal use, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatics, antineoplastic agents, antiobesity preparations, antipruritics, antithrombotics, antivirals for systemic use, beta blocking agents, calcium channel blockers, cardiac therapy, corticosteroids, cough and cold preparations, diuretics, lipid modifying agents, nasal preparations, thyroid therapy, urologicals, vaccines, psycholeptics, psycoanaleptics, ophthalmologicals, general nutrients, mineral supplements, muscle relaxants, vitamins, drugs used in diabetes, sex hormones and modulators of the genital system, immunosuppresants, drugs for acid related disorders etc.
Outcome measures
| Measure |
Fremanezumab
n=43 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
DB Period: Number of Participants Who Received Concomitant Medications
|
43 Participants
|
42 Participants
|
SECONDARY outcome
Timeframe: Week 12 up to Week 24Population: OL-ITT analysis set included only participants who received at least 1 dose of study drug during the open-label treatment period.
Concomitant medications included: agents acting on renin-angiotensin system, analgesics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antiemetics and antinauseants, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatics, antineoplastic agents, antithrombotics, beta blocking agents, calcium channel blockers, corticosteroids for systemic use, cough and cold preparations, diuretics, lipid modifying agents, nasal preparations, other gynecologicals, other nervous system drugs, thyroid therapy, unspecified herbal and traditional medicine, urologicals, vaccines, psycholeptics, psycoanaleptics, general nutrients, mineral supplements, muscle relaxants, vitamins, sex hormones and modulators of the genital system, drugs for acid related disorders, drugs for constipation, drugs for obstructive airways disease etc.
Outcome measures
| Measure |
Fremanezumab
n=9 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=7 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
OL Period: Number of Participants Who Received Concomitant Medications
|
9 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1) up to Week 24Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.
eC-SSRS is a questionnaire to assess suicidal ideation (severity and intensity) and behavior. Suicidal ideation: A series of 1 -5 questions (with 'yes' or 'no' response) with 5 types of ideation of increasing severity: 1. wish to be dead, 2. non-specific active suicidal thoughts, 3. active suicidal ideation with any methods (not plan) without intent to act, 4. active suicidal ideation with some intent to act, without specific plan, 5. active suicidal ideation with specific plan and intent. A positive finding was defined as a 'yes' response to question 4 or 5.
Outcome measures
| Measure |
Fremanezumab
n=43 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
Number of Participants With Positive Findings on Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1) up to Week 24Population: ITT analysis set included all randomized participants.
Number of participants with treatment-emergent antidrug antibodies reported.
Outcome measures
| Measure |
Fremanezumab
n=44 Participants
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Antidrug Antibodies (ADA)
|
0 Participants
|
0 Participants
|
Adverse Events
Fremanezumab
Placebo
Serious adverse events
| Measure |
Fremanezumab
n=43 participants at risk
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 participants at risk
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
0.00%
0/43 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/43 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/43 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
0.00%
0/43 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Vascular disorders
Hypotension
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
0.00%
0/43 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
Other adverse events
| Measure |
Fremanezumab
n=43 participants at risk
Participants received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
Placebo
n=43 participants at risk
Participants received placebo matched to fremanezumab administered as 3 SC injections (1.5 mL each) at randomization (Week 0), Weeks 4, and 8 during the DB treatment period. Participants who completed the DB treatment period and continued into the OL treatment period received fremanezumab 675 mg administered as 3 SC injections (225 mg/1.5 mL each) at Weeks 12, 16, and 20 during the OL treatment period.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.0%
3/43 • Number of events 4 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
4.7%
2/43 • Number of events 2 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Gastrointestinal disorders
Nausea
|
9.3%
4/43 • Number of events 6 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
4.7%
2/43 • Number of events 2 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
General disorders
Injection site erythema
|
25.6%
11/43 • Number of events 30 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
32.6%
14/43 • Number of events 41 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
General disorders
Injection site induration
|
41.9%
18/43 • Number of events 60 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
32.6%
14/43 • Number of events 49 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
General disorders
Injection site pain
|
32.6%
14/43 • Number of events 48 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
34.9%
15/43 • Number of events 47 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
General disorders
Injection site pruritus
|
9.3%
4/43 • Number of events 8 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
4.7%
2/43 • Number of events 2 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Influenza
|
7.0%
3/43 • Number of events 3 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
2.3%
1/43 • Number of events 2 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
2/43 • Number of events 3 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
9.3%
4/43 • Number of events 4 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Pneumonia
|
7.0%
3/43 • Number of events 3 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
0.00%
0/43 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Sinusitis
|
9.3%
4/43 • Number of events 5 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
7.0%
3/43 • Number of events 4 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
11.6%
5/43 • Number of events 5 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Investigations
International normalised ratio increased
|
9.3%
4/43 • Number of events 4 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
2.3%
1/43 • Number of events 1 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Nervous system disorders
Dizziness
|
9.3%
4/43 • Number of events 4 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
4.7%
2/43 • Number of events 2 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
|
Nervous system disorders
Headache
|
14.0%
6/43 • Number of events 7 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
4.7%
2/43 • Number of events 3 • Baseline (Day -28 to Day -1) up to Week 24
Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
|
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