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A Study to Test if Fremanezumab Reduces Headache in Participants With Posttraumatic Headache (PTH)

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ClinicalTrials.gov Identifier: NCT03347188
Recruitment Status : Completed
First Posted : November 20, 2017
Results First Posted : March 26, 2021
Last Update Posted : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Post-Traumatic Headache
Interventions Drug: Fremanezumab
Drug: Placebo
Enrollment 87
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description 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. 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.
Period Title: Double-blind (DB) Period (12 Weeks)
Started 44 43
Received at Least 1 Dose of Study Drug 43 43
Full Analysis Set (FAS) [1] 42 43
Completed 29 26
Not Completed 15 17
Reason Not Completed
Protocol Violation             2             2
Withdrawal by Subject             4             8
Lost to Follow-up             7             4
Adverse Event             1             1
Other than specified             1             2
[1]
Received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment on primary endpoint.
Period Title: Open-label (OL) Period (12 Weeks)
Started 35 35
Entered in OL Period for Anti-drug Antibody (ADA) Only 26 28
Received at Least 1 Dose of Study Drug 9 7
Completed 8 6
Not Completed 27 29
Reason Not Completed
Entered for ADA assessment only, not treated             26             28
Withdrawal by Subject             1             0
Other than specified             0             1
Arm/Group Title Fremanezumab Placebo Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 44 43 87
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) analysis set included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 43 participants 87 participants
42.6  (13.01) 43.8  (14.48) 43.2  (13.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 43 participants 87 participants
Female
25
  56.8%
25
  58.1%
50
  57.5%
Male
19
  43.2%
18
  41.9%
37
  42.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 43 participants 87 participants
Hispanic or Latino
4
   9.1%
4
   9.3%
8
   9.2%
Not Hispanic or Latino
40
  90.9%
38
  88.4%
78
  89.7%
Unknown or Not Reported
0
   0.0%
1
   2.3%
1
   1.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 44 participants 43 participants 87 participants
White
41
  93.2%
39
  90.7%
80
  92.0%
Black or African American
3
   6.8%
1
   2.3%
4
   4.6%
Native Hawaiian or other Pacific Islander
0
   0.0%
1
   2.3%
1
   1.1%
Other
0
   0.0%
2
   4.7%
2
   2.3%
Number of Headache Days of at Least Moderate Severity   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 43 participants 43 participants 86 participants
18.7  (7.03) 18.5  (6.12) 18.6  (6.56)
[1]
Measure Analysis Population Description: 'Number analyzed' signifies participants evaluable for this baseline measure.
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day -28 to Day -1), up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 43
Least Squares Mean (Standard Error)
Unit of Measure: days
-3.6  (0.99) -5.1  (1.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fremanezumab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1876
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-0.73 to 3.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.11
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day -28 to Day-1) up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 43
Measure Type: Count of Participants
Unit of Measure: Participants
5
  11.9%
4
   9.3%
3.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day -28 to Day-1) up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 43
Measure Type: Count of Participants
Unit of Measure: Participants
9
  21.4%
11
  25.6%
4.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline (Day -28 to Day-1) up to Months 1, 2, and 3
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 43
Measure Type: Count of Participants
Unit of Measure: Participants
Month 1 Number Analyzed 42 participants 43 participants
8
  19.0%
11
  25.6%
Month 2 Number Analyzed 38 participants 41 participants
8
  21.1%
14
  34.1%
Month 3 Number Analyzed 37 participants 37 participants
14
  37.8%
12
  32.4%
5.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline (Day -28 to Day -1), up to Months 1, 2, and 3
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 43
Least Squares Mean (Standard Error)
Unit of Measure: days
Change at Month 1 Number Analyzed 42 participants 43 participants
-3.6  (0.97) -4.0  (0.99)
Change at Month 2 Number Analyzed 38 participants 41 participants
-3.7  (1.06) -6.7  (1.06)
Change at Month 3 Number Analyzed 37 participants 37 participants
-5.2  (1.20) -7.2  (1.21)
6.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day -28 to Day -1), Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 35 37
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-6.9  (4.54) -10.8  (4.65)
7.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Weeks 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 42 43
Measure Type: Count of Participants
Unit of Measure: Participants
Week 4 Responder
12
  28.6%
11
  25.6%
Non-Responder
24
  57.1%
26
  60.5%
Missing
6
  14.3%
6
  14.0%
Week 8 Responder
14
  33.3%
17
  39.5%
Non-Responder
20
  47.6%
21
  48.8%
Missing
8
  19.0%
5
  11.6%
Week 12 Responder
11
  26.2%
16
  37.2%
Non-Responder
20
  47.6%
16
  37.2%
Missing
11
  26.2%
11
  25.6%
8.Secondary Outcome
Title DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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.
Time Frame Baseline (Day -28 to -1) up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 43 43
Measure Type: Count of Participants
Unit of Measure: Participants
31
  72.1%
35
  81.4%
9.Secondary Outcome
Title OL Period: Number of Participants With TEAEs
Hide Description 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.
Time Frame Week 12 up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
OL-ITT analysis set included only participants who received at least 1 dose of study drug during the open-label treatment period.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 7
Measure Type: Count of Participants
Unit of Measure: Participants
8
  88.9%
6
  85.7%
10.Secondary Outcome
Title DB Period: Number of Participants Who Did Not Complete the Study
Hide Description Number of participants who did not complete the study due to any reason and due to AEs are reported.
Time Frame Baseline (Day -28 to Day -1) up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 43 43
Measure Type: Count of Participants
Unit of Measure: Participants
Discontinued study due to any reason
15
  34.9%
17
  39.5%
Discontinued study due to AEs
1
   2.3%
1
   2.3%
11.Secondary Outcome
Title OL Period: Number of Participants Who Did Not Complete the Study
Hide Description Number of participants who did not complete the study due to any reason and due to AEs are reported.
Time Frame Week 12 up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
OL-ITT analysis set included only participants who received at least 1 dose of study drug during the open-label treatment period.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 7
Measure Type: Count of Participants
Unit of Measure: Participants
Discontinued study due to any reason
1
  11.1%
1
  14.3%
Discontinued study due to AEs
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title DB Period: Number of Participants Who Received Concomitant Medications
Hide Description 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.
Time Frame Baseline (Day -28 to Day -1) up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 43 43
Measure Type: Count of Participants
Unit of Measure: Participants
43
 100.0%
42
  97.7%
13.Secondary Outcome
Title OL Period: Number of Participants Who Received Concomitant Medications
Hide Description 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.
Time Frame Week 12 up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
OL-ITT analysis set included only participants who received at least 1 dose of study drug during the open-label treatment period.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 9 7
Measure Type: Count of Participants
Unit of Measure: Participants
9
 100.0%
7
 100.0%
14.Secondary Outcome
Title Number of Participants With Positive Findings on Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
Hide Description 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.
Time Frame Baseline (Day -28 to Day -1) up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 43 43
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Number of Participants With Treatment-Emergent Antidrug Antibodies (ADA)
Hide Description Number of participants with treatment-emergent antidrug antibodies reported.
Time Frame Baseline (Day -28 to Day -1) up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all randomized participants.
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 44 43
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
Time Frame Baseline (Day -28 to Day -1) up to Week 24
Adverse Event Reporting Description Safety analysis set included all randomized participants who received at least 1 dose of the study drug.
 
Arm/Group Title Fremanezumab Placebo
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Fremanezumab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)      0/43 (0.00%)    
Hide Serious Adverse Events
Fremanezumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/43 (4.65%)      1/43 (2.33%)    
Gastrointestinal disorders     
Gastrointestinal haemorrhage  1  1/43 (2.33%)  1 0/43 (0.00%)  0
General disorders     
Non-cardiac chest pain  1  0/43 (0.00%)  0 1/43 (2.33%)  1
Hepatobiliary disorders     
Cholelithiasis  1  0/43 (0.00%)  0 1/43 (2.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  1/43 (2.33%)  1 0/43 (0.00%)  0
Vascular disorders     
Hypotension  1  1/43 (2.33%)  1 0/43 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fremanezumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/43 (65.12%)      29/43 (67.44%)    
Gastrointestinal disorders     
Diarrhoea  1  3/43 (6.98%)  4 2/43 (4.65%)  2
Nausea  1  4/43 (9.30%)  6 2/43 (4.65%)  2
General disorders     
Injection site erythema  1  11/43 (25.58%)  30 14/43 (32.56%)  41
Injection site induration  1  18/43 (41.86%)  60 14/43 (32.56%)  49
Injection site pain  1  14/43 (32.56%)  48 15/43 (34.88%)  47
Injection site pruritus  1  4/43 (9.30%)  8 2/43 (4.65%)  2
Infections and infestations     
Influenza  1  3/43 (6.98%)  3 1/43 (2.33%)  2
Nasopharyngitis  1  2/43 (4.65%)  3 4/43 (9.30%)  4
Pneumonia  1  3/43 (6.98%)  3 0/43 (0.00%)  0
Sinusitis  1  4/43 (9.30%)  5 3/43 (6.98%)  4
Upper respiratory tract infection  1  1/43 (2.33%)  1 5/43 (11.63%)  5
Investigations     
International normalised ratio increased  1  4/43 (9.30%)  4 1/43 (2.33%)  1
Nervous system disorders     
Dizziness  1  4/43 (9.30%)  4 2/43 (4.65%)  2
Headache  1  6/43 (13.95%)  7 2/43 (4.65%)  3
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products R&D, Inc.
Phone: 1-888-483-8279
EMail: USMedInfo@tevapharm.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )
ClinicalTrials.gov Identifier: NCT03347188    
Other Study ID Numbers: TV48125-CNS-20024
First Submitted: November 14, 2017
First Posted: November 20, 2017
Results First Submitted: February 22, 2021
Results First Posted: March 26, 2021
Last Update Posted: April 8, 2021