Trial Outcomes & Findings for A Study Comparing the Efficacy and Safety of Fremanezumab (TEV-48125) for the Prevention of Chronic Cluster Headache (CCH) (NCT NCT02964338)

Last Updated: 2021-11-09

Results Overview

A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States \[US\]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Change from baseline in the overall monthly average number of CH attacks during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

259 participants

Primary outcome timeframe

Baseline Period (from at least Week -4 to Week 0), Up to Week 12

Results posted on

2021-11-09

Participant Flow

Participants with a history of chronic cluster headache (CCH) were enrolled. Eligible participants entered baseline cluster headache (CH) attack information into an electronic diary device daily for greater than or equal to (≥)4 weeks during the Baseline Period.

A total of 259 participants were randomly assigned with stratification based on sex, country, and baseline concomitant preventive medication use (yes/no) to either placebo, fremanezumab 675/225/225 milligrams (mg), or fremanezumab 900/225/225 mg treatment groups in a 1:1:1 ratio.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 milliliters \[mL\]) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Overall Study STARTED	84	88	87
Overall Study Safety Analysis Set	83	88	87
Overall Study Full Analysis Set	81	86	87
Overall Study COMPLETED	67	64	68
Overall Study NOT COMPLETED	17	24	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 milliliters \[mL\]) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Overall Study Sponsor terminated study for futility	12	15	14
Overall Study Lack of Efficacy	0	3	0
Overall Study Lost to Follow-up	1	0	3
Overall Study Protocol Violation	0	1	0
Overall Study Withdrawal by Subject	1	3	1
Overall Study Adverse Event	2	1	1
Overall Study Non-compliant with e-diary	0	1	0
Overall Study Did not meet criteria	1	0	0

Baseline Characteristics

A Study Comparing the Efficacy and Safety of Fremanezumab (TEV-48125) for the Prevention of Chronic Cluster Headache (CCH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=84 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Total n=259 Participants Total of all reporting groups
Age, Continuous	46.3 years STANDARD_DEVIATION 11.29 • n=5 Participants	45.3 years STANDARD_DEVIATION 11.40 • n=7 Participants	43.8 years STANDARD_DEVIATION 12.92 • n=5 Participants	45.1 years STANDARD_DEVIATION 11.90 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	36 Participants n=7 Participants	36 Participants n=5 Participants	107 Participants n=4 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	52 Participants n=7 Participants	51 Participants n=5 Participants	152 Participants n=4 Participants
Race/Ethnicity, Customized White	79 participants n=5 Participants	83 participants n=7 Participants	79 participants n=5 Participants	241 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants	16 participants n=4 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Race/Ethnicity, Customized Middle Eastern	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	77 participants n=5 Participants	78 participants n=7 Participants	83 participants n=5 Participants	238 participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 participants n=5 Participants	9 participants n=7 Participants	4 participants n=5 Participants	18 participants n=4 Participants
Race/Ethnicity, Customized Missing Ethnicity	2 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Number of CH Attacks During the Baseline Period	38.0 CH attacks STANDARD_DEVIATION 33.88 • n=5 Participants	33.9 CH attacks STANDARD_DEVIATION 27.37 • n=7 Participants	44.0 CH attacks STANDARD_DEVIATION 43.78 • n=5 Participants	38.6 CH attacks STANDARD_DEVIATION 35.75 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline Period (from at least Week -4 to Week 0), Up to Week 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessments by the Week 12 assessment.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=86 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Mean Change From Baseline in the Overall Monthly Average Number of CH Attacks Up to Week 12	-12.2 CH attacks/month Standard Error 2.32	-8.7 CH attacks/month Standard Error 2.26	-15.5 CH attacks/month Standard Error 2.24

SECONDARY outcome

Timeframe: Baseline Period (from at least Week -4 to Week 0) up to Week 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessments by the Week 12 assessment.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=86 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Percentage of Participants With a ≥50% Reduction From Baseline in the Monthly Average Number of CH Attacks Up to Week 12	40 percentage of participants	40 percentage of participants	45 percentage of participants

SECONDARY outcome

Timeframe: Baseline Period (from at least Week -4 to Week 0), Week 4 and Week 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessments by the Week 12 assessment. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.

A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) ≥1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Mean change from baseline in monthly average number of CH attacks during 4-week period after administration of first dose of study drug (based on Week 0 to 4 data) and during 4-week period after administration of third dose of study drug (based on Week 8 to 12 data) is reported.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=86 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Mean Change From Baseline in the Monthly Average Number of CH Attacks at Week 4 and Week 12 Change at Week 4	-10.4 CH attacks/month Standard Deviation 17.22	-7.7 CH attacks/month Standard Deviation 19.53	-15.0 CH attacks/month Standard Deviation 24.17
Mean Change From Baseline in the Monthly Average Number of CH Attacks at Week 4 and Week 12 Change at Week 12	-12.6 CH attacks/month Standard Deviation 25.72	-3.1 CH attacks/month Standard Deviation 34.42	-17.9 CH attacks/month Standard Deviation 25.98

SECONDARY outcome

Timeframe: Baseline Period (from at least Week -4 to Week 0), Up to Week 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessments by the Week 12 assessment.

A maximum of 2 concomitant preventive medications for CH were allowed during the study. Participants must have been on a stable dose and regimen of the concomitant medication for at least 2 weeks before screening and throughout the study. Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=86 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Mean Change From Baseline in the Overall Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) Up to Week 12 Change at Week 12	-0.7 days of use/week Standard Deviation 1.34	-0.8 days of use/week Standard Deviation 1.57	-0.8 days of use/week Standard Deviation 1.20
Mean Change From Baseline in the Overall Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) Up to Week 12 Baseline	2.4 days of use/week Standard Deviation 2.42	2.4 days of use/week Standard Deviation 2.18	2.2 days of use/week Standard Deviation 2.27

SECONDARY outcome

Timeframe: Baseline Period (from at least Week -4 to Week 0), Up to Week 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessments by the Week 12 assessment.

Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat CCH during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=86 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat CCH Up to Week 12 Baseline	2.2 days of use/week Standard Deviation 2.59	1.9 days of use/week Standard Deviation 2.53	1.9 days of use/week Standard Deviation 2.59
Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat CCH Up to Week 12 Change at Week 12	-0.5 days of use/week Standard Deviation 1.35	-0.5 days of use/week Standard Deviation 1.35	-0.5 days of use/week Standard Deviation 1.09

SECONDARY outcome

Timeframe: Baseline and Weeks 1, 4, 8, and 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessments by the Week 12 assessment.

The PPSI assessment was developed to measure pain intensity and was adjusted for CH symptoms improvement. Participants marked the level of CH-associated pain and indicated if pain is "1=much worse," "2=moderately worse," "3=slightly worse," "4=unchanged," "5=slightly improved," "6=moderately improved," or "7=much improved" compared with 4 weeks prior. PPSI was defined as the change in pain that corresponds with a minimal rating of "5=slightly improved." Data at Week 1 was recorded on Day 7 in the electronic diary device at home. Week 12 data also included assessment at the early withdrawal visit for participants who discontinued the study early.

Outcome measures

Outcome measures
Measure	Placebo n=81 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=86 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much worse, Baseline	3 Participants	1 Participants	1 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately worse, Baseline	1 Participants	4 Participants	4 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly worse, Baseline	1 Participants	5 Participants	4 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Unchanged, Baseline	69 Participants	72 Participants	75 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly improved, Baseline	5 Participants	3 Participants	3 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately improved, Baseline	1 Participants	1 Participants	0 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much improved, Baseline	1 Participants	0 Participants	0 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Missing, Baseline	0 Participants	0 Participants	0 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much worse, Week 1	0 Participants	3 Participants	3 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately worse, Week 1	0 Participants	2 Participants	1 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly worse, Week 1	0 Participants	2 Participants	5 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Unchanged, Week 1	35 Participants	31 Participants	26 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly improved, Week 1	23 Participants	20 Participants	32 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately improved, Week 1	5 Participants	4 Participants	8 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much improved, Week 1	6 Participants	13 Participants	8 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Missing, Week 1	12 Participants	11 Participants	4 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much worse, Week 4	0 Participants	1 Participants	0 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately worse, Week 4	1 Participants	2 Participants	3 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly worse, Week 4	1 Participants	2 Participants	2 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Unchanged, Week 4	24 Participants	24 Participants	25 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly improved, Week 4	30 Participants	17 Participants	25 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately improved, Week 4	5 Participants	9 Participants	12 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much improved, Week 4	12 Participants	18 Participants	11 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Missing, Week 4	8 Participants	13 Participants	9 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much worse, Week 8	3 Participants	2 Participants	0 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately worse, Week 8	1 Participants	3 Participants	3 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly worse, Week 8	3 Participants	4 Participants	5 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Unchanged, Week 8	27 Participants	18 Participants	24 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly improved, Week 8	18 Participants	12 Participants	13 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately improved, Week 8	10 Participants	13 Participants	14 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much improved, Week 8	4 Participants	12 Participants	15 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Missing, Week 8	15 Participants	22 Participants	13 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much worse, Week 12	0 Participants	2 Participants	1 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately worse, Week 12	3 Participants	5 Participants	3 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly worse, Week 12	4 Participants	6 Participants	6 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Unchanged, Week 12	29 Participants	27 Participants	31 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Slightly improved, Week 12	21 Participants	18 Participants	15 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Moderately improved, Week 12	8 Participants	11 Participants	11 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Much improved, Week 12	13 Participants	14 Participants	12 Participants
Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12 Missing, Week 12	3 Participants	3 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the Investigator on a scale of mild, moderate and severe, with severe as an AE that prevents usual activities. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Adverse Events (AEs) Any AE	43 Participants	51 Participants	49 Participants
Number of Participants With Adverse Events (AEs) Severe AE	3 Participants	1 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Treatment-related AE	17 Participants	23 Participants	28 Participants
Number of Participants With Adverse Events (AEs) Serious AE	2 Participants	2 Participants	3 Participants
Number of Participants With Adverse Events (AEs) AE leading to discontinuation	2 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

Serum chemistry, hematology, urinalysis laboratory tests with potentially clinically significant abnormal findings included: Alanine Aminotransferase (units/liter \[U/L\]) ≥3\*upper limit of normal (ULN); Aspartate Aminotransferase (U/L) ≥3\*ULN; Bilirubin (Total) ≥34.2 micromole/liter (umol/L); Blood Urea Nitrogen ≥10.71 millimole (mmol)/L; Creatinine ≥177 umol/L; Gamma Glutamyl Transferase (U/L) ≥3\*ULN; hemoglobin less than (\<)115 grams (g)/L (males) or less than or equal to (≤)95 g/L (females); leukocytes ≥20\*10\^9/L or ≤3\*10\^9/L; Eosinophils/Leukocytes ≥10%; Hematocrit \<0.37 L/L (males) and \<0.32 L/L (females); platelets ≥700\*10\^9/L or ≤75\*10\^9/L; blood ≥2 unit increase from baseline; urine glucose (milligrams/decilitre \[mg/dL\]) ≥2 U increase from baseline; ketones (mg/dL) ≥2 U increase from baseline; urine protein (mg/dL) ≥2 U increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results With at least 1 serum chemistry abnormality	1 Participants	2 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results With at least 1 hematology abnormality	2 Participants	1 Participants	3 Participants
Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results With at least 1 urinalysis abnormality	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable at the timepoint.

Coagulation parameters included: prothrombin time (PT) (seconds) and prothrombin international normalized ratio (INR). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). Missing PT and prothrombin INR shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Low-Low	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Low-Normal	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Low-High	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Normal-Low	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Normal-Normal	68 Participants	69 Participants	62 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Normal-High	3 Participants	2 Participants	5 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: High-Low	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: High-Normal	5 Participants	8 Participants	11 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: High-High	5 Participants	4 Participants	3 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results PT: Missing	2 Participants	5 Participants	6 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Low-Low	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Low-Normal	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Low-High	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Normal-Low	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Normal-Normal	70 Participants	71 Participants	69 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Normal-High	4 Participants	2 Participants	5 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: High-Low	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: High-Normal	5 Participants	7 Participants	6 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: High-High	2 Participants	3 Participants	1 Participants
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results Prothrombin INR: Missing	2 Participants	5 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

Potentially clinically significant abnormal vital signs findings included: pulse rate ≤50 beats/minute (bpm) and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease of ≥20 mmHg, or ≥180 mmHg and increase of ≥20 mmHg; diastolic blood pressure ≤50 mmHg and decrease of ≥15 mmHg, or ≥105 mmHg and increase of ≥15 mmHg; respiratory rate \<10 breaths/minute; and body temperature ≥38.3 degrees centigrade and change of ≥1.1 degrees centigrade. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values	3 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies participants evaluable at the timepoint.

ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. Missing ECG shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters Normal / Normal	47 Participants	46 Participants	45 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters Normal / NCS	8 Participants	11 Participants	14 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters Normal / CS	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters NCS / Normal	10 Participants	7 Participants	8 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters NCS / NCS	15 Participants	20 Participants	12 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters NCS / CS	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters CS / Normal	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters CS / NCS	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters CS / CS	0 Participants	0 Participants	0 Participants
Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters Missing	3 Participants	4 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 were offered without a threshold applied. Injection site reactions included injection site erythema, induration, pain, haemorrhage, bruising, hypersensitivity, swelling, rash, and flushing. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Injection Site Reactions Injection site erythema	3 Participants	7 Participants	5 Participants
Number of Participants With Injection Site Reactions Injection site induration	3 Participants	6 Participants	6 Participants
Number of Participants With Injection Site Reactions Injection site pain	6 Participants	5 Participants	2 Participants
Number of Participants With Injection Site Reactions Injection site haemorrhage	0 Participants	0 Participants	2 Participants
Number of Participants With Injection Site Reactions Injection site bruising	0 Participants	0 Participants	1 Participants
Number of Participants With Injection Site Reactions Injection site hypersensitivity	0 Participants	1 Participants	0 Participants
Number of Participants With Injection Site Reactions Injection site swelling	2 Participants	0 Participants	0 Participants
Number of Participants With Injection Site Reactions Injection site rash	1 Participants	0 Participants	0 Participants
Number of Participants With Injection Site Reactions Injection site flushing	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: Safety population included all randomized participants who received at least 1 dose of study drug.

eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 Participants Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 Participants Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Fremanezumab 675/225/225 mg

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Fremanezumab 900/225/225 mg

Serious events: 3 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=83 participants at risk Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 participants at risk Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 participants at risk Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Infections and infestations Pelvic abscess	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/87 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/88 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/87 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis acute	1.2% 1/83 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/87 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Infusion site necrosis	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/87 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/87 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Immune system disorders Anaphylactic reaction	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/88 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/87 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Cellulitis	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/87 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Conversion disorder	1.2% 1/83 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/87 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Surgical and medical procedures Hospitalisation	0.00% 0/83 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/88 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	1.1% 1/87 • Number of events 1 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Placebo n=83 participants at risk Participants received placebo via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injections at Weeks 4 and 8.	Fremanezumab 675/225/225 mg n=88 participants at risk Participants received placebo via an approximately 1-hour intravenous infusion and fremanezumab at 675 mg as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.	Fremanezumab 900/225/225 mg n=87 participants at risk Participants received fremanezumab at 900 mg via an approximately 1-hour intravenous infusion and placebo administered as 3 subcutaneous injections at Week 0 followed by fremanezumab at 225 mg administered as single subcutaneous injections (225 mg/1.5 mL) at Weeks 4 and 8.
Gastrointestinal disorders Nausea	4.8% 4/83 • Number of events 4 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	5.7% 5/88 • Number of events 5 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	3.4% 3/87 • Number of events 4 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Injection site erythema	3.6% 3/83 • Number of events 4 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	8.0% 7/88 • Number of events 15 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	5.7% 5/87 • Number of events 6 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Injection site induration	3.6% 3/83 • Number of events 8 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	6.8% 6/88 • Number of events 12 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	6.9% 6/87 • Number of events 12 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Injection site pain	7.2% 6/83 • Number of events 11 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	5.7% 5/88 • Number of events 9 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	2.3% 2/87 • Number of events 2 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	7.2% 6/83 • Number of events 7 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	6.8% 6/88 • Number of events 7 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.	9.2% 8/87 • Number of events 9 • Baseline up to Week 12 Safety population included all randomized participants who received at least 1 dose of study drug.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
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Restriction type: OTHER