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

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03347188
• Collaborator: (none)
• Enrollment: 87
• Locations: 33
• Arms: 2
• Actual Duration (Months): 29.5
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of fremanezumab in adult participants aged 18 to 70 years, inclusive, for the prevention of PTH. The study will include a double-blind (DB) treatment period (12 weeks) and an open-label (OL) treatment period (12 weeks).

Condition or Disease	Intervention/Treatment	Phase
Post-Traumatic Headache	Drug: Fremanezumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 2, Multicenter, Randomized, Proof-of-Concept, Double-Blind, Placebo-Controlled, Parallel-Group Study, Including an Open-Label Period, Evaluating the Efficacy and Safety of 1 Subcutaneous Dose Regimen of Fremanezumab for the Treatment of Posttraumatic Headache (PTH)
• Actual Study Start Date: Dec 18, 2017
• Actual Primary Completion Date: Mar 13, 2020
• Actual Study Completion Date: Jun 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fremanezumab Participants will receive 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 DB treatment period. Participants who complete the DB treatment period and continue into the OL treatment period will receive 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.	Drug: Fremanezumab; Fremanezumab will be administered per dose and schedule specified in the arm.; Other Names: TEV-48125
Placebo Comparator: Placebo Participants will receive placebo matching 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 complete the DB treatment period and continue into the OL treatment period will receive 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.	Drug: Placebo; Placebo matching to fremanezumab will be administered per schedule specified in the arm.

Outcome Measures

Primary Outcome Measures

1. 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 [Baseline (Day -28 to Day -1), up to Week 12]

   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.

Secondary Outcome Measures

1. 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 [Baseline (Day -28 to Day-1) up to Week 12]

   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.

2. 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 [Baseline (Day -28 to Day-1) up to Week 12]

   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.

3. 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) [Baseline (Day -28 to Day-1) up to Months 1, 2, and 3]

   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.

4. 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) [Baseline (Day -28 to Day -1), up to Months 1, 2, and 3]

   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.

5. 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 [Baseline (Day -28 to Day -1), Week 12]

   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.

6. 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 [Weeks 4, 8, and 12]

   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.

7. DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline (Day -28 to -1) up to Week 12]

   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.

8. OL Period: Number of Participants With TEAEs [Week 12 up to Week 24]

   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.

9. DB Period: Number of Participants Who Did Not Complete the Study [Baseline (Day -28 to Day -1) up to Week 12]

   Number of participants who did not complete the study due to any reason and due to AEs are reported.

10. OL Period: Number of Participants Who Did Not Complete the Study [Week 12 up to Week 24]

    Number of participants who did not complete the study due to any reason and due to AEs are reported.

11. DB Period: Number of Participants Who Received Concomitant Medications [Baseline (Day -28 to Day -1) up to Week 12]

    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.

12. OL Period: Number of Participants Who Received Concomitant Medications [Week 12 up to Week 24]

    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.

13. Number of Participants With Positive Findings on Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) [Baseline (Day -28 to Day -1) up to Week 24]

    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.

14. Number of Participants With Treatment-Emergent Antidrug Antibodies (ADA) [Baseline (Day -28 to Day -1) up to Week 24]

    Number of participants with treatment-emergent antidrug antibodies reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant has a body weight greater than or equal to (≥) 45 kilograms (kg).

• Traumatic injury to the head has occurred, defined as a structural or functional injury resulting from the action of external forces.

• The participant has a diagnosis of PTH.

• The participant is not using preventive medications for headache.

• Women of childbearing potential whose male partners are potentially fertile (that is, no vasectomy) must use highly effective birth control methods for the duration of the study and for 30 weeks after the last study drug administration. Men must be sterile or, if they are potentially fertile or reproductively competent (that is, not surgically or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, acceptable birth control methods for the duration of the study and for 30 weeks after the last study drug administration.

NOTE- Additional criteria apply, please contact the investigator for more information.

Exclusion Criteria:

• The participant has a previous history of brain imaging showing evidence of intracerebral hemorrhage, subdural or epidural hematomas, or subarachnoid hemorrhage as a consequence of the traumatic head injury. Brain images with structurally insignificant changes, as discussed and approved by the sponsor, will be reviewed by the sponsor on a case-by-case basis.

• The participant has PTH attributed to craniotomy.

• The participant has whiplash and subsequent headache but no history of head injury or concussion.

• The participant is using analgesic medications containing opioids (including codeine) or a barbiturate on average more than 15 days per month.

• The participant has had exposure to a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway (erenumab, eptinezumab, galcanezumab, and fremanezumab) during the 6 months prior to the day of the screening visit.

• The participant is currently being treated with onabotulinumtoxinA (for example, Botox, Dysport, Xeomin) application in the head or neck or received any such injection during the 3 months prior to the screening visit.

• The participant has been implanted with any electronic devices for headache prevention during the 3 months prior to the screening visit or is currently using any implanted or externally applied stimulator or device.

• The participant has been treated with a nerve block for head and/or neck during the 3 months prior to the screening visit.

• The participant is a pregnant or lactating woman or plans to become pregnant during the study.

NOTE- Additional criteria apply, please contact the investigator for more information.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 14065	Phoenix	Arizona	United States	85018
2	Teva Investigational Site 14069	Scottsdale	Arizona	United States	85259-5452
3	Teva Investigational Site 14048	Little Rock	Arkansas	United States	72205
4	Teva Investigational Site 30236	Little Rock	Arkansas	United States	72205
5	Teva Investigational Site 14052	Long Beach	California	United States	90806
6	Teva Investigational Site 14053	Los Angeles	California	United States	90073
7	Teva Investigational Site 14060	San Diego	California	United States	92161
8	Teva Investigational Site 14054	San Francisco	California	United States	94109
9	Teva Investigational Site 14045	Fairfield	Connecticut	United States	06824
10	Teva Investigational Site 14063	Miami	Florida	United States	33136
11	Teva Investigational Site 14041	North Miami	Florida	United States	33161
12	Teva Investigational Site 14056	Tampa	Florida	United States	33609
13	Teva Investigational Site 14057	Riverwoods	Illinois	United States	60015
14	Teva Investigational Site 14067	Indianapolis	Indiana	United States	46256
15	Teva Investigational Site 14058	Louisville	Kentucky	United States	40207
16	Teva Investigational Site 14061	Waltham	Massachusetts	United States	02451
17	Teva Investigational Site 14051	Kansas City	Missouri	United States	64128-2226
18	Teva Investigational Site 14046	Saint Louis	Missouri	United States	63141
19	Teva Investigational Site 14043	Springfield	Missouri	United States	65810
20	Teva Investigational Site 14119	Albany	New York	United States	12208
21	Teva Investigational Site 14229	Amherst	New York	United States	14226
22	Teva Investigational Site 14118	Bronx	New York	United States	10467
23	Teva Investigational Site 14047	New York	New York	United States	10021
24	Teva Investigational Site 14114	Durham	North Carolina	United States	27713
25	Teva Investigational Site 14059	Salisbury	North Carolina	United States	28144
26	Teva Investigational Site 14049	Portland	Oregon	United States	97225
27	Teva Investigational Site 14064	Philadelphia	Pennsylvania	United States	19107
28	Teva Investigational Site 14040	Pittsburgh	Pennsylvania	United States	15236
29	Teva Investigational Site 14230	Nashville	Tennessee	United States	37203
30	Teva Investigational Site 14055	Dallas	Texas	United States	75390-8565
31	Teva Investigational Site 14050	Waco	Texas	United States	76711
32	Teva Investigational Site 14113	Spokane	Washington	United States	99202
33	Teva Investigational Site 14044	Morgantown	West Virginia	United States	26506

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 30, 2020
• Statistical Analysis Plan - Apr 6, 2020

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT03347188
• Other Study ID Numbers: TV48125-CNS-20024
• First Posted: Nov 20, 2017
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: posttraumatic headache (PTH)
• Additional relevant MeSH terms: Post-Traumatic Headache; Headache

Study Results

Participant Flow

Arm/Group Title	Fremanezumab	Placebo
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)	42	43
COMPLETED	29	26
NOT COMPLETED	15	17
Period Title: Double-blind (DB) 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

Baseline Characteristics

Arm/Group Title	Fremanezumab	Placebo	Total
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 Participants	44	43	87
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.6 (13.01)	43.8 (14.48)	43.2 (13.68)
Sex: Female, Male (Count of Participants)
Female	25 56.8%	25 58.1%	50 57.5%
Male	19 43.2%	18 41.9%	37 42.5%
Ethnicity (NIH/OMB) (Count of 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%	1 2.3%	1 1.1%
Race/Ethnicity, Customized (Count of Participants)
White	41 93.2%	39 90.7%	80 92%
Black or African American	3 6.8%	1 2.3%	4 4.6%
Native Hawaiian or other Pacific Islander	0 0%	1 2.3%	1 1.1%
Other	0 0%	2 4.7%	2 2.3%
Number of Headache Days of at Least Moderate Severity (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	18.7 (7.03)	18.5 (6.12)	18.6 (6.56)

Outcome Measures

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
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

Outcome Measure Data

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
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.
Measure Participants	42	43
Least Squares Mean (Standard Error) [days]	-3.6 (0.99)	-5.1 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fremanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1876
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
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

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
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

Outcome Measure Data

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
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.
Measure Participants	42	43
Count of Participants [Participants]	5 11.4%	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
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

Outcome Measure Data

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
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.
Measure Participants	42	43
Count of Participants [Participants]	9 20.5%	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)
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

Outcome Measure Data

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
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.
Measure Participants	42	43
Month 1	8 18.2%	11 25.6%
Month 2	8 18.2%	14 32.6%
Month 3	14 31.8%	12 27.9%

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)
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

Outcome Measure Data

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
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.
Measure Participants	42	43
Change at Month 1	-3.6 (0.97)	-4.0 (0.99)
Change at Month 2	-3.7 (1.06)	-6.7 (1.06)
Change at Month 3	-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
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

Outcome Measure Data

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
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.
Measure Participants	35	37
Least Squares Mean (Standard Error) [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
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

Outcome Measure Data

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
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.
Measure Participants	42	43
Responder	12 27.3%	11 25.6%
Non-Responder	24 54.5%	26 60.5%
Missing	6 13.6%	6 14%
Responder	14 31.8%	17 39.5%
Non-Responder	20 45.5%	21 48.8%
Missing	8 18.2%	5 11.6%
Responder	11 25%	16 37.2%
Non-Responder	20 45.5%	16 37.2%
Missing	11 25%	11 25.6%

8. Secondary Outcome

Title	DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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

Outcome Measure Data

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
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.
Measure Participants	43	43
Count of Participants [Participants]	31 70.5%	35 81.4%

9. Secondary Outcome

Title	OL Period: Number of Participants With TEAEs
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

Outcome Measure Data

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
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.
Measure Participants	9	7
Count of Participants [Participants]	8 18.2%	6 14%

10. Secondary Outcome

Title	DB Period: Number of Participants Who Did Not Complete the Study
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

Outcome Measure Data

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
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.
Measure Participants	43	43
Discontinued study due to any reason	15 34.1%	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
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

Outcome Measure Data

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
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.
Measure Participants	9	7
Discontinued study due to any reason	1 2.3%	1 2.3%
Discontinued study due to AEs	0 0%	0 0%

12. Secondary Outcome

Title	DB Period: Number of Participants Who Received Concomitant Medications
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

Outcome Measure Data

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
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.
Measure Participants	43	43
Count of Participants [Participants]	43 97.7%	42 97.7%

13. Secondary Outcome

Title	OL Period: Number of Participants Who Received Concomitant Medications
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

Outcome Measure Data

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
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.
Measure Participants	9	7
Count of Participants [Participants]	9 20.5%	7 16.3%

14. Secondary Outcome

Title	Number of Participants With Positive Findings on Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
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

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab	Placebo
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.
Measure Participants	43	43
Count of Participants [Participants]	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Antidrug Antibodies (ADA)
Description	Number of participants with treatment-emergent antidrug antibodies reported.
Time Frame	Baseline (Day -28 to Day -1) up to Week 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all randomized participants.

Arm/Group Title	Fremanezumab	Placebo
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.
Measure Participants	44	43
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/43 (0%)
Serious Adverse Events
	Fremanezumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/43 (4.7%)		1/43 (2.3%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/43 (2.3%)	1	0/43 (0%)	0
General disorders
Non-cardiac chest pain	0/43 (0%)	0	1/43 (2.3%)	1
Hepatobiliary disorders
Cholelithiasis	0/43 (0%)	0	1/43 (2.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/43 (2.3%)	1	0/43 (0%)	0
Vascular disorders
Hypotension	1/43 (2.3%)	1	0/43 (0%)	0
Other (Not Including Serious) Adverse Events
	Fremanezumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/43 (65.1%)		29/43 (67.4%)
Gastrointestinal disorders
Diarrhoea	3/43 (7%)	4	2/43 (4.7%)	2
Nausea	4/43 (9.3%)	6	2/43 (4.7%)	2
General disorders
Injection site erythema	11/43 (25.6%)	30	14/43 (32.6%)	41
Injection site induration	18/43 (41.9%)	60	14/43 (32.6%)	49
Injection site pain	14/43 (32.6%)	48	15/43 (34.9%)	47
Injection site pruritus	4/43 (9.3%)	8	2/43 (4.7%)	2
Infections and infestations
Influenza	3/43 (7%)	3	1/43 (2.3%)	2
Nasopharyngitis	2/43 (4.7%)	3	4/43 (9.3%)	4
Pneumonia	3/43 (7%)	3	0/43 (0%)	0
Sinusitis	4/43 (9.3%)	5	3/43 (7%)	4
Upper respiratory tract infection	1/43 (2.3%)	1	5/43 (11.6%)	5
Investigations
International normalised ratio increased	4/43 (9.3%)	4	1/43 (2.3%)	1
Nervous system disorders
Dizziness	4/43 (9.3%)	4	2/43 (4.7%)	2
Headache	6/43 (14%)	7	2/43 (4.7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.